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Tj 3.084375 0 Td 59.244792 Tz (461; ) Tj 1.684375 0 Td 59.244792 Tz (534/800; ) Tj 3.084375 0 Td 60.15625 Tz (544/250, ) Tj 3.10625 0 Td 59.244792 Tz (279; ) Tj 40 0 0 40 0 2693 Tm 51.925 0 Td 72.02381 Tz (5467256 ) Tj 51.428571 0 0 51.428571 0 2650.068702 Tm 27.261111 0 Td 58.333333 Tz (See ) Tj 1.186111 0 Td 49.200337 Tz (application ) Tj 3.461111 0 Td 38.078704 Tz (file ) Tj 1.108333 0 Td 47.530864 Tz (for ) Tj 0.991667 0 Td 55.497685 Tz (complete ) Tj 2.858333 0 Td 51.311728 Tz (search ) Tj 2.022222 0 Td 44.965278 Tz (history. ) Tj 42.857143 0 0 42.857143 0 2574.460568 Tm 30.38 0 Td 59.305556 Tz (\(56\) ) Tj 7.373333 0 Td 66.111111 Tz (References ) Tj 4.223333 0 Td 66.888889 Tz (Cited ) Tj 38.571429 0 0 38.571429 0 2499 Tm 41.922222 0 Td 95.421811 Tz (PUBLICATIONS ) Tj 45.714286 0 0 45.714286 0 2426.373171 Tm 28.48125 0 Td 41.015625 Tz (Parrill, ) Tj 2.1875 0 Td 48.763021 Tz ("Virtual ) Tj 2.58125 0 Td 51.446759 Tz (screening ) Tj 2.953125 0 Td 55.052083 Tz (approaches ) Tj 3.54375 0 Td 46.180556 Tz (for ) Tj 1.028125 0 Td 49.826389 Tz (the ) Tj 1.1375 0 Td 45.3125 Tz (identification ) Tj 4.025 0 Td 58.333333 Tz (of ) Tj 0.853125 0 Td 72.916667 Tz (non ) Tj 45.714286 0 0 45.714286 0 2387.1181 Tm 28.459375 0 Td 44.479167 Tz (lipid ) Tj 1.728125 0 Td 50.231481 Tz (autotaxin ) Tj 3.171875 0 Td 45.269097 Tz (inhibitors'. ) Tj 3.740625 0 Td 52.864583 Tz (Bioorganic ) Tj 3.5875 0 Td 91.145833 Tz (& ) Tj 1.00625 0 Td 54.282407 Tz (Medicinal ) Tj 3.346875 0 Td 57.118056 Tz (Chemistry ) Tj 45.714286 0 0 45.714286 0 2345.796296 Tm 28.459375 0 Td 50.520833 Tz (\(2008\), ) Tj 2.40625 0 Td 45.572917 Tz (16\(4\), ) Tj 1.79375 0 Td 52.256944 Tz (pp. ) Tj 1.225 0 Td 54.024621 Tz (1784-1795.* ) Tj 45.714286 0 0 45.714286 0 2310.280702 Tm 28.48125 0 Td 55.902778 Tz (Hoeglund, ) Tj 3.45625 0 Td 50.183824 Tz (Characterization ) Tj 5.6 0 Td 54.6875 Tz (of ) Tj 1.028125 0 Td 49.421296 Tz (non-lipid ) Tj 3.084375 0 Td 50.231481 Tz (autotaxin ) Tj 3.15 0 Td 45.572917 Tz (inhibitors'. ) Tj 45.714286 0 0 45.714286 0 2275.879747 Tm 28.48125 0 Td 52.864583 Tz (Bioorganic ) Tj 3.36875 0 Td 83.854167 Tz (& ) Tj 0.765625 0 Td 54.282407 Tz (Medicinal ) Tj 3.10625 0 Td 56.712963 Tz (Chemistry ) Tj 3.2375 0 Td 50 Tz (\(2010\), ) Tj 2.3625 0 Td 46.788194 Tz (18\(2\), ) Tj 1.88125 0 Td 48.611111 Tz (pp. ) Tj 1.071875 0 Td 54.6875 Tz (769-776.* ) Tj 51.428571 0 0 51.428571 0 2197.112782 Tm 25.336111 0 Td 48.611111 Tz (* ) Tj 0.505556 0 Td 47.314815 Tz (cited ) Tj 1.594444 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 57.118056 Tz (examiner ) Tj 51.428571 0 0 51.428571 0 2120.6289 Tm 25.297222 0 Td 57.407407 Tz (Primary ) Tj 2.683333 0 Td 57.928241 Tz (Examiner ) Tj 2.916667 0 Td 116.666667 Tz ( ) Tj 0.836111 0 Td 51.851852 Tz (Sreeni ) Tj 2.061111 0 Td 61.868687 Tz (Padmanabhan ) Tj 40 0 0 40 0 2083 Tm 32.475 0 Td 63.425926 Tz (Assistant ) Tj 3.725 0 Td 75 Tz (Examiner ) Tj 3.8 0 Td 145.833333 Tz ( ) Tj 1.075 0 Td 72.5 Tz (Sahar ) Tj 2.35 0 Td 75 Tz (Javanmard ) Tj 51.428571 0 0 51.428571 0 2035.39267 Tm 25.316667 0 Td 49.421296 Tz (\(74\) ) Tj 1.536111 0 Td 48.251029 Tz (Attorney, ) Tj 2.916667 0 Td 50.771605 Tz (Agent, ) Tj 2.158333 0 Td 55.092593 Tz (or ) Tj 0.952778 0 Td 56.712963 Tz (Firm ) Tj 1.555556 0 Td 116.666667 Tz ( ) Tj 0.836111 0 Td 56.018519 Tz (William ) Tj 2.644444 0 Td 46.990741 Tz (S. ) Tj 0.913889 0 Td 48.070988 Tz (Parks; ) Tj 2.041667 0 Td 51.851852 Tz (Wyatt, ) Tj 48.571429 0 0 48.571429 0 1994 Tm 26.785294 0 Td 52.941176 Tz (Tarrant ) Tj 2.388235 0 Td 96.078431 Tz (& ) Tj 0.802941 0 Td 65.767974 Tz (Combs, ) Tj 2.594118 0 Td 74.346405 Tz (LLP ) Tj 45 0 0 45 0 1921.151515 Tm 28.933333 0 Td 56.481481 Tz (\(57\) ) Tj 7.688889 0 Td 93.981481 Tz (ABSTRACT ) Tj 51.428571 0 0 51.428571 0 1860.743073 Tm 25.297222 0 Td 51.851852 Tz (Classes ) Tj 2.488889 0 Td 61.574074 Tz (of ) Tj 0.933333 0 Td 62.294239 Tz (compounds ) Tj 3.713889 0 Td 45.37037 Tz (that ) Tj 1.380556 0 Td 48.611111 Tz (exhibit ) Tj 2.352778 0 Td 46.450617 Tz (effective ) Tj 2.838889 0 Td 46.990741 Tz (inhibition ) Tj 3.15 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1822.663391 Tm 25.297222 0 Td 50.05144 Tz (autotaxin ) Tj 2.936111 0 Td 60.185185 Tz (enzymes ) Tj 2.741667 0 Td 50.771605 Tz (are ) Tj 1.127778 0 Td 50.771605 Tz (provided. ) Tj 3.013889 0 Td 59.143519 Tz (Such ) Tj 1.652778 0 Td 48.148148 Tz (classes ) Tj 2.275 0 Td 50.462963 Tz (include ) Tj 2.333333 0 Td 57.523148 Tz (thio ) Tj 51.428571 0 0 51.428571 0 1782.941615 Tm 25.277778 0 Td 48.070988 Tz (ureas, ) Tj 2.119444 0 Td 50.487329 Tz (diphenyldiazerenes, ) Tj 6.125 0 Td 51.527778 Tz (Xanthenes, ) Tj 3.441667 0 Td 59.41358 Tz (and ) Tj 1.458333 0 Td 48.611111 Tz (isoindoles ) Tj 3.266667 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1743.795181 Tm 25.297222 0 Td 48.148148 Tz (exhibit ) Tj 2.177778 0 Td 45.046296 Tz (reactivity ) Tj 2.877778 0 Td 53.472222 Tz (with ) Tj 1.419444 0 Td 50.411523 Tz (autotaxin ) Tj 2.916667 0 Td 43.75 Tz (to ) Tj 0.7 0 Td 48.935185 Tz 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2.236111 0 Td 46.450617 Tz (effective ) Tj 2.722222 0 Td 46.990741 Tz (inhibition ) Tj 3.033333 0 Td 59.953704 Tz (of ) Tj 51.428571 0 0 51.428571 0 2192.666667 Tm 6.358333 0 Td 50.05144 Tz (autotaxin ) Tj 2.936111 0 Td 60.185185 Tz (enzymes ) Tj 2.741667 0 Td 50.771605 Tz (are ) Tj 1.127778 0 Td 50.771605 Tz (provided. ) Tj 3.013889 0 Td 59.143519 Tz (Such ) Tj 1.652778 0 Td 48.148148 Tz (classes ) Tj 2.275 0 Td 50.462963 Tz (include ) Tj 2.352778 0 Td 56.712963 Tz (thio ) Tj 51.428571 0 0 51.428571 0 2148.937965 Tm 6.338889 0 Td 48.070988 Tz (ureas, ) Tj 2.119444 0 Td 50.487329 Tz (diphenyldiazerenes, ) Tj 6.125 0 Td 51.527778 Tz (Xanthenes, ) Tj 3.441667 0 Td 59.41358 Tz (and ) Tj 1.458333 0 Td 48.611111 Tz (isoindoles ) Tj 3.266667 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 2104.785542 Tm 6.358333 0 Td 48.148148 Tz (exhibit ) Tj 2.197222 0 Td 44.722222 Tz (reactivity ) Tj 2.858333 0 Td 53.472222 Tz (with ) Tj 1.419444 0 Td 50.411523 Tz (autotaxin ) Tj 2.916667 0 Td 43.75 Tz (to ) Tj 0.7 0 Td 48.935185 Tz (ultimately ) Tj 3.130556 0 Td 53.472222 Tz (reduce ) Tj 2.061111 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 46.990741 Tz (size ) Tj 51.428571 0 0 51.428571 0 2060.900889 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.875 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 46.990741 Tz (reactive ) Tj 2.508333 0 Td 42.777778 Tz (sites ) Tj 1.555556 0 Td 51.388889 Tz (thereon ) Tj 2.430556 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 52.314815 Tz (prevent ) Tj 2.430556 0 Td 52.175926 Tz (conversion ) Tj 3.402778 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 59.953704 Tz (lyso ) Tj 51.428571 0 0 51.428571 0 2020.24497 Tm 6.358333 0 Td 53.898635 Tz (phosphatidylcholine ) Tj 6.377778 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 51.419753 Tz (lysophophatidic ) Tj 4.861111 0 Td 45.37037 Tz (acid. ) Tj 1.633333 0 Td 52.391975 Tz (Furthermore, ) Tj 51.428571 0 0 51.428571 0 1976.723247 Tm 6.377778 0 Td 54.282407 Tz (Such ) Tj 1.536111 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 54.012346 Tz (can ) Tj 1.205556 0 Td 58.333333 Tz (be ) Tj 0.894444 0 Td 51.041667 Tz (incorporated ) Tj 3.908333 0 Td 50.771605 Tz (within ) Tj 2.080556 0 Td 48.206019 Tz (delivery ) Tj 2.566667 0 Td 55.740741 Tz (forms ) Tj 51.428571 0 0 51.428571 0 1931.189937 Tm 6.358333 0 Td 48.611111 Tz (for ) Tj 1.108333 0 Td 65.462963 Tz (human ) Tj 2.236111 0 Td 46.990741 Tz (ingestion. ) Tj 3.072222 0 Td 64.814815 Tz (As ) Tj 1.069444 0 Td 49.259259 Tz (such, ) Tj 1.75 0 Td 49.907407 Tz (these ) Tj 1.75 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 54.552469 Tz (accord ) Tj 2.197222 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 1888.360097 Tm 6.358333 0 Td 48.611111 Tz (excellent ) Tj 2.858333 0 Td 61.033951 Tz (manner ) Tj 2.411111 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 46.843434 Tz (potentially ) Tj 3.325 0 Td 53.472222 Tz (reducing ) Tj 2.780556 0 Td 50.87963 Tz (generation ) Tj 3.325 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 60.493827 Tz (cer ) Tj 51.428571 0 0 51.428571 0 1844.808635 Tm 6.338889 0 Td 46.990741 Tz (tain ) Tj 1.225 0 Td 51.851852 Tz (cancers ) Tj 2.294444 0 Td 45.910494 Tz (attributable ) Tj 3.422222 0 Td 46.990741 Tz (to ) Tj 0.661111 0 Td 50.771605 Tz (the ) Tj 0.991667 0 Td 53.877315 Tz (presence ) Tj 2.683333 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 47.530864 Tz (naturally ) Tj 2.722222 0 Td 51.49177 Tz (occurring ) Tj 51.428571 0 0 51.428571 0 1799.547264 Tm 6.358333 0 Td 50.05144 Tz (autotaxin ) Tj 2.975 0 Td 51.311728 Tz (within ) Tj 2.158333 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 65.462963 Tz (human ) Tj 2.236111 0 Td 51.851852 Tz (body. ) Tj 1.886111 0 Td 60.648148 Tz (Methods ) Tj 2.8 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 47.530864 Tz (inactivating ) Tj 51.428571 0 0 51.428571 0 1755.828784 Tm 6.358333 0 Td 50.05144 Tz (autotaxin ) Tj 2.955556 0 Td 45.37037 Tz (to ) Tj 0.816667 0 Td 46.296296 Tz (certain ) Tj 2.216667 0 Td 52.314815 Tz (degrees ) Tj 2.45 0 Td 50.05144 Tz (therewith ) Tj 2.975 0 Td 55.902778 Tz (Such ) Tj 1.575 0 Td 61.934156 Tz (compounds ) Tj 3.597222 0 Td 49.691358 Tz (are ) Tj 51.428571 0 0 51.428571 0 1712.985075 Tm 6.358333 0 Td 58.922559 Tz (encompassed ) Tj 4.063889 0 Td 51.851852 Tz (within ) Tj 2.061111 0 Td 49.331276 Tz (invention ) Tj 2.877778 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 46.666667 Tz (well. ) Tj 38.571429 0 0 38.571429 0 1611 Tm 12.366667 0 Td 112.345679 Tz (BACKGROUND ) Tj 6.974074 0 Td 101.54321 Tz (OF ) Tj 1.451852 0 Td 106.584362 Tz (THE ) Tj 2.177778 0 Td 94.197531 Tz (PRIOR ) Tj 3.033333 0 Td 103.703704 Tz (ART ) Tj 48.571429 0 0 48.571429 0 1505 Tm 7.514706 0 Td 54.215686 Tz (Autotaxin, ) Tj 3.438235 0 Td 50.612745 Tz (also ) Tj 1.4 0 Td 68.627451 Tz (known ) Tj 2.244118 0 Td 53.186275 Tz (as ) Tj 0.782353 0 Td 69.485294 Tz (ATX, ) Tj 1.873529 0 Td 74.117647 Tz (ENPP2 ) Tj 2.408824 0 Td 54.901961 Tz (or ) Tj 0.782353 0 Td 66.568627 Tz (NPP2, ) Tj 2.202941 0 Td 50.784314 Tz (short ) Tj 1.688235 0 Td 51.470588 Tz (for ) Tj 51.428571 0 0 51.428571 0 1464.076923 Tm 6.377778 0 Td 51.851852 Tz (Ectonucleotide ) Tj 4.588889 0 Td 54.660494 Tz (pyrophosphatase ) Tj 5.172222 0 Td 52.423747 Tz (phosphodiesterase ) Tj 5.619444 0 Td 58.333333 Tz (2 ) Tj 0.641667 0 Td 38.888889 Tz (is ) Tj 0.719444 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 1416.9388 Tm 6.358333 0 Td 63.194444 Tz (enzyme ) Tj 2.469444 0 Td 49.826389 Tz (secreted ) Tj 2.566667 0 Td 51.311728 Tz (within ) Tj 2.061111 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 66.111111 Tz (human ) Tj 2.197222 0 Td 52.5 Tz (body. ) Tj 1.75 0 Td 54.282407 Tz (This ) Tj 1.555556 0 Td 55.092593 Tz (molecule ) Tj 2.819444 0 Td 54.012346 Tz (has ) Tj 51.428571 0 0 51.428571 0 1375.265497 Tm 6.338889 0 Td 58.333333 Tz (been ) Tj 1.497222 0 Td 65.462963 Tz (known ) Tj 2.1 0 Td 48.611111 Tz (for ) Tj 0.952778 0 Td 51.527778 Tz (generating ) Tj 3.208333 0 Td 59.62963 Tz (\(LPA\) ) Tj 1.886111 0 Td 53.703704 Tz (through ) Tj 2.391667 0 Td 52.824074 Tz (conversion ) Tj 3.286111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 59.953704 Tz (lyso ) Tj 51.428571 0 0 51.428571 0 1333.53271 Tm 6.358333 0 Td 51.203704 Tz (phosphatidyl-choline ) Tj 6.280556 0 Td 60.925926 Tz (\(LPC\) ) Tj 1.983333 0 Td 47.222222 Tz (thereto ) Tj 2.177778 0 Td 46.450617 Tz (via ) Tj 1.011111 0 Td 52.614379 Tz (lysophospholipase ) Tj 5.522222 0 Td 81.018519 Tz (D ) Tj 51.428571 0 0 51.428571 0 1287.782609 Tm 6.358333 0 Td 44.965278 Tz (activity ) Tj 2.469444 0 Td 46.990741 Tz (\(the ) Tj 1.438889 0 Td 55.555556 Tz (removal ) Tj 2.644444 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 50.925926 Tz (choline ) Tj 2.430556 0 Td 58.333333 Tz (from ) Tj 1.730556 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 55.092593 Tz (base ) Tj 1.594444 0 Td 65.219907 Tz (compound ) Tj 51.428571 0 0 51.428571 0 1242.362319 Tm 6.358333 0 Td 50.771605 Tz (generates ) Tj 2.916667 0 Td 55.740741 Tz (LPA\). ) Tj 1.866667 0 Td 71.296296 Tz (LPA ) Tj 1.419444 0 Td 52.932099 Tz (has ) Tj 1.108333 0 Td 57.523148 Tz (been ) Tj 1.516667 0 Td 47.800926 Tz (realized ) Tj 2.45 0 Td 45.37037 Tz (to ) Tj 0.680556 0 Td 48.935185 Tz (contribute ) Tj 3.072222 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 58.333333 Tz (tumor ) Tj 51.428571 0 0 51.428571 0 1201.400955 Tm 6.358333 0 Td 43.75 Tz (cell ) Tj 1.205556 0 Td 52.777778 Tz (growth, ) Tj 2.372222 0 Td 48.148148 Tz (unfortunately, ) Tj 4.180556 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 45.046296 Tz (reactivity ) Tj 2.877778 0 Td 50.771605 Tz (within ) Tj 1.963889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 68.055556 Tz (human ) Tj 51.428571 0 0 51.428571 0 1154.767263 Tm 6.338889 0 Td 60.763889 Tz (body ) Tj 1.711111 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 71.296296 Tz (LPA ) Tj 1.555556 0 Td 50.771605 Tz (within ) Tj 2.1 0 Td 46.759259 Tz (certain ) Tj 2.236111 0 Td 45.833333 Tz (tissues ) Tj 2.177778 0 Td 54.012346 Tz (has ) Tj 1.263889 0 Td 45.730453 Tz (resulted, ) Tj 2.722222 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 48.148148 Tz (certain ) Tj 51.428571 0 0 51.428571 0 1112.223827 Tm 6.377778 0 Td 45.37037 Tz (studies, ) Tj 2.352778 0 Td 58.333333 Tz (of ) Tj 0.758333 0 Td 54.012346 Tz (cancerous ) Tj 3.091667 0 Td 56.018519 Tz (growths ) Tj 2.527778 0 Td 64.814815 Tz (when ) Tj 1.711111 0 Td 50.925926 Tz (present ) Tj 2.294444 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 46.759259 Tz (certain ) Tj 2.158333 0 Td 43.055556 Tz (levels. ) Tj 51.428571 0 0 51.428571 0 1067.044335 Tm 6.377778 0 Td 48.611111 Tz (In ) Tj 0.738889 0 Td 43.75 Tz (this ) Tj 1.225 0 Td 55.092593 Tz (manner, ) Tj 2.488889 0 Td 47.314815 Tz (then, ) Tj 1.594444 0 Td 32.407407 Tz (it ) Tj 0.525 0 Td 54.012346 Tz (has ) Tj 1.108333 0 Td 57.523148 Tz (been ) Tj 1.555556 0 Td 50.411523 Tz (theorized ) Tj 2.858333 0 Td 46.990741 Tz (that ) Tj 1.263889 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 49.074074 Tz (greater ) Tj 2.197222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1026.915212 Tm 6.358333 0 Td 51.851852 Tz (incidence ) Tj 3.033333 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 50.411523 Tz (autotaxin ) Tj 2.975 0 Td 44.965278 Tz (activity ) Tj 2.411111 0 Td 51.311728 Tz (within ) Tj 2.119444 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 66.111111 Tz (human ) Tj 2.255556 0 Td 52.5 Tz (body, ) Tj 1.847222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 987.206388 Tm 6.358333 0 Td 49.074074 Tz (greater ) Tj 2.236111 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 45.959596 Tz (possibility ) Tj 3.208333 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 70.216049 Tz (LPA ) Tj 1.458333 0 Td 48.905724 Tz (generation. ) Tj 3.422222 0 Td 84.259259 Tz (A ) Tj 0.7 0 Td 50.411523 Tz (reduction ) Tj 2.936111 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 944.989899 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.722222 0 Td 45.910494 Tz (capabilities ) Tj 3.558333 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 50.05144 Tz (autotaxin ) Tj 2.994444 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 51.388889 Tz (convert ) Tj 2.430556 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 72.376543 Tz (LPC ) Tj 1.594444 0 Td 74.537037 Tz (mol ) Tj 51.428571 0 0 51.428571 0 903.050292 Tm 6.358333 0 Td 51.203704 Tz (ecule ) Tj 1.652778 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 71.296296 Tz (LPA ) Tj 1.4 0 Td 60.277778 Tz (would ) Tj 1.886111 0 Td 46.866097 Tz (theoretically ) Tj 3.772222 0 Td 55.902778 Tz (permitan ) Tj 2.838889 0 Td 49.421296 Tz (ultimate ) Tj 2.508333 0 Td 50.771605 Tz (reduction ) Tj 51.428571 0 0 51.428571 0 862.356718 Tm 6.358333 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 45.959596 Tz (possibility ) Tj 3.208333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 59.143519 Tz (unwanted ) Tj 2.994444 0 Td 43.75 Tz (cell ) Tj 1.225 0 Td 46.367521 Tz (proliferation ) Tj 3.811111 0 Td 53.703704 Tz (through ) Tj 2.45 0 Td 55.092593 Tz (reduced ) Tj 51.428571 0 0 51.428571 0 822.277247 Tm 6.377778 0 Td 71.296296 Tz (LPA ) Tj 1.477778 0 Td 53.472222 Tz (presence ) Tj 2.722222 0 Td 51.311728 Tz (within ) Tj 2.041667 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 47.530864 Tz (subjects ) Tj 2.761111 0 Td 52.5 Tz (body. ) Tj 51.428571 0 0 51.428571 0 765.601467 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.263889 0 Td 60.853909 Tz (mechanism ) Tj 3.422222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 50.05144 Tz (autotaxin ) Tj 2.838889 0 Td 55.092593 Tz (interms ) Tj 2.45 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 55.452675 Tz (enzymatic ) Tj 3.130556 0 Td 45.37037 Tz (activity ) Tj 51.428571 0 0 51.428571 0 725.091371 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.090535 Tz (catalysis ) Tj 2.761111 0 Td 43.75 Tz (to ) Tj 0.816667 0 Td 58.333333 Tz (form ) Tj 1.711111 0 Td 70.216049 Tz (LPA ) Tj 1.516667 0 Td 48.148148 Tz (resides ) Tj 2.275 0 Td 45.37037 Tz (in ) Tj 0.816667 0 Td 37.808642 Tz (its ) Tj 0.933333 0 Td 52.423747 Tz (phosphodiesterase ) Tj 51.428571 0 0 51.428571 0 684.394366 Tm 6.358333 0 Td 45.075758 Tz (capability. ) Tj 3.286111 0 Td 71.296296 Tz (LPA ) Tj 1.536111 0 Td 56.17284 Tz (can ) Tj 1.283333 0 Td 56.712963 Tz (be ) Tj 0.933333 0 Td 52.572016 Tz (generated ) Tj 3.111111 0 Td 56.712963 Tz (from ) Tj 1.652778 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 52.662037 Tz (cleavage ) Tj 2.780556 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 640.282667 Tm 6.358333 0 Td 53.347578 Tz (phophodiester ) Tj 4.394444 0 Td 58.333333 Tz (bonds ) Tj 2.041667 0 Td 59.953704 Tz (of ) Tj 0.952778 0 Td 61.574074 Tz (LPC, ) Tj 1.788889 0 Td 48.611111 Tz (as ) Tj 0.894444 0 Td 51.041667 Tz (well ) Tj 1.536111 0 Td 51.851852 Tz (as ) Tj 0.933333 0 Td 37.808642 Tz (its ) Tj 0.972222 0 Td 50.231481 Tz (function ) Tj 2.702778 0 Td 51.851852 Tz (as ) Tj 0.933333 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 600.700885 Tm 6.358333 0 Td 53.596866 Tz (phospholipase ) Tj 4.336111 0 Td 63.194444 Tz (enzyme ) Tj 2.45 0 Td 50.555556 Tz (\(note ) Tj 1.730556 0 Td 57.407407 Tz (Formula ) Tj 2.625 0 Td 33.487654 Tz (I\). ) Tj 31.428571 0 0 31.428571 0 482 Tm 35.35 0 Td 74.242424 Tz (Formula ) Tj 3.372727 0 Td 53.030303 Tz (I ) Tj 31.428571 0 0 31.428571 0 423 Tm 19.472727 0 Td 111.363636 Tz (O ) Tj 6.427273 0 Td 106.060606 Tz (H ) Tj 65.714286 0 0 65.714286 0 321.328895 Tm 4.976087 0 Td 183.559783 Tz (S-N-a-N- ) Tj 10.591304 0 Td 35.084541 Tz (C17H33 ) Tj 1.673913 0 Td 75.241546 Tz (ATX ) Tj 50 0 0 50 0 288.875 Tm 6.72 0 Td 60 Tz (1. ) Tj 1.02 0 Td 60 Tz (\\ ) Tj 4.5 0 Td 70 Tz (OH ) Tj 31.428571 0 0 31.428571 0 256 Tm 30.672727 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 224 Tm 21.986364 0 Td 93.686869 Tz (LPC ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.775 0 Td 74.537037 Tz (2 ) Tj 40 0 0 40 0 2913 Tm 41.825 0 Td 66.666667 Tz (-continued ) Tj 91.428571 0 0 91.428571 0 2844 Tm 18.867188 0 Td 47.395833 Tz (" ) Tj 50 0 0 50 0 2792.459184 Tm 28.8 0 Td 116 Tz (to--o ) Tj 7.68 0 Td 70 Tz (O ) Tj 2.32 0 Td 46.111111 Tz (C17H33 ) Tj 2.08 0 Td 53.333333 Tz (+ ) Tj 73.571429 0 0 73.571429 0 2748.295455 Tm 20.741748 0 Td 47.572816 Tz (OH ) Tj 4.98835 0 Td 104.20712 Tz (r ) Tj 31.428571 0 0 31.428571 0 2719 Tm 59.85 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2687 Tm 54.281818 0 Td 93.686869 Tz (LPA ) Tj 31.428571 0 0 31.428571 0 2649 Tm 68.536364 0 Td 111.363636 Tz (OH ) Tj 53.571429 0 0 53.571429 0 2619.9 Tm 36.045333 0 Td 121.333333 Tz (N ) Tj 1.512 0 Td 146.222222 Tz (1N1 ) Tj 85.714286 0 0 85.714286 0 2561 Tm 22.528333 0 Td 77.777778 Tz (1\\ ) Tj 31.428571 0 0 31.428571 0 2529 Tm 64.336364 0 Td 65.151515 Tz (choline ) Tj 51.428571 0 0 51.428571 0 2448.038926 Tm 25.316667 0 Td 46.990741 Tz (In ) Tj 1.011111 0 Td 46.616809 Tz (extracellular ) Tj 4.063889 0 Td 42.12963 Tz (fluids, ) Tj 2.216667 0 Td 42.939815 Tz (this ) Tj 1.458333 0 Td 55.092593 Tz (enzymatic ) Tj 3.383333 0 Td 46.8107 Tz (catalysis ) Tj 2.955556 0 Td 58.333333 Tz (of ) Tj 1.069444 0 Td 71.296296 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 2406.116129 Tm 25.297222 0 Td 57.87037 Tz (removes ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 50.925926 Tz (choline ) Tj 2.372222 0 Td 52.391975 Tz (group, ) Tj 2.177778 0 Td 50 Tz (leaving ) Tj 2.391667 0 Td 59.953704 Tz (LPA, ) Tj 1.711111 0 Td 58.333333 Tz (which ) Tj 2.022222 0 Td 54.012346 Tz (has ) Tj 1.225 0 Td 55.092593 Tz (a ) Tj 0.583333 0 Td 62.654321 Tz (ten ) Tj 51.428571 0 0 51.428571 0 2365.907455 Tm 25.297222 0 Td 57.685185 Tz (dency ) Tj 1.963889 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 49.331276 Tz (stimulate ) Tj 2.916667 0 Td 42.939815 Tz (cell ) Tj 1.283333 0 Td 56.712963 Tz (growth ) Tj 2.313889 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.367521 Tz (proliferation ) Tj 3.888889 0 Td 48.611111 Tz (as ) Tj 0.855556 0 Td 51.851852 Tz (well ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 2323.3 Tm 25.297222 0 Td 52.441077 Tz (chemotaxis. ) Tj 3.752778 0 Td 63.194444 Tz (From ) Tj 1.730556 0 Td 41.481481 Tz (this, ) Tj 1.477778 0 Td 32.407407 Tz (it ) Tj 0.583333 0 Td 52.777778 Tz (appears ) Tj 2.45 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 46.990741 Tz (motility ) Tj 2.488889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 59.62963 Tz (tumor ) Tj 51.428571 0 0 51.428571 0 2282.626943 Tm 25.297222 0 Td 44.074074 Tz (cells ) Tj 1.613889 0 Td 38.888889 Tz (is ) Tj 0.738889 0 Td 51.131687 Tz (increased ) Tj 3.013889 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 47.962963 Tz (well, ) Tj 1.730556 0 Td 46.8107 Tz (resulting ) Tj 2.780556 0 Td 46.990741 Tz (in ) Tj 0.836111 0 Td 48.287037 Tz (properties ) Tj 3.188889 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 57.523148 Tz (gene ) Tj 51.428571 0 0 51.428571 0 2239.54933 Tm 25.297222 0 Td 51.527778 Tz (expression ) Tj 3.305556 0 Td 51.311728 Tz (within ) Tj 2.080556 0 Td 46.296296 Tz (certain ) Tj 2.158333 0 Td 55.092593 Tz (carcinomas ) Tj 3.538889 0 Td 51.851852 Tz (\(Such ) Tj 1.75 0 Td 44.290123 Tz (as, ) Tj 1.011111 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 47.170782 Tz (instance, ) Tj 51.428571 0 0 51.428571 0 2198.713043 Tm 25.277778 0 Td 49.151235 Tz (breast ) Tj 1.983333 0 Td 54.012346 Tz (cancer ) Tj 2.138889 0 Td 41.666667 Tz (cells\), ) Tj 2.022222 0 Td 52.314815 Tz (causing ) Tj 2.430556 0 Td 48.148148 Tz (further ) Tj 2.216667 0 Td 51.851852 Tz (processing ) Tj 3.344444 0 Td 46.990741 Tz (into ) Tj 1.380556 0 Td 55.092593 Tz (a ) Tj 0.563889 0 Td 58.333333 Tz (form ) Tj 51.428571 0 0 51.428571 0 2157.184178 Tm 25.277778 0 Td 46.990741 Tz (that ) Tj 1.380556 0 Td 38.888889 Tz (is ) Tj 0.7 0 Td 49.331276 Tz (bioactive ) Tj 2.897222 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 47.43266 Tz (potentially ) Tj 3.402778 0 Td 52.175926 Tz (dangerous. ) Tj 3.422222 0 Td 50.555556 Tz (Metastasis ) Tj 3.305556 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 2115.993412 Tm 25.297222 0 Td 53.619529 Tz (oncogenesis ) Tj 3.869444 0 Td 58.333333 Tz (of ) Tj 0.933333 0 Td 52.391975 Tz (cancer ) Tj 2.197222 0 Td 44.074074 Tz (cells ) Tj 1.613889 0 Td 55.092593 Tz (appear ) Tj 2.275 0 Td 43.75 Tz (to ) Tj 0.875 0 Td 55.092593 Tz (occur ) Tj 1.925 0 Td 50.231481 Tz (as ) Tj 0.913889 0 Td 51.851852 Tz (well ) Tj 1.575 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 2074.536618 Tm 25.297222 0 Td 49.826389 Tz (elevated ) Tj 2.761111 0 Td 45.37037 Tz (levels ) Tj 2.002778 0 Td 59.953704 Tz (of ) Tj 1.011111 0 Td 70.216049 Tz (LPA ) Tj 1.594444 0 Td 50.925926 Tz (present ) Tj 2.508333 0 Td 50.771605 Tz (within ) Tj 2.197222 0 Td 51.851852 Tz (a ) Tj 0.680556 0 Td 48.611111 Tz (targeted ) Tj 2.702778 0 Td 47.222222 Tz (region. ) Tj 51.428571 0 0 51.428571 0 2031.55122 Tm 25.316667 0 Td 51.49177 Tz (Increased ) Tj 2.916667 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 51.527778 Tz (expression ) Tj 3.286111 0 Td 52.932099 Tz (has ) Tj 1.147222 0 Td 56.712963 Tz (been ) Tj 1.575 0 Td 45.694444 Tz (identified ) Tj 2.916667 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 46.666667 Tz (renal ) Tj 1.594444 0 Td 55.740741 Tz (carci ) Tj 51.428571 0 0 51.428571 0 1990.269368 Tm 25.297222 0 Td 59.62963 Tz (noma, ) Tj 2.002778 0 Td 48.611111 Tz (metastatic ) Tj 3.091667 0 Td 48.611111 Tz (breast ) Tj 1.925 0 Td 48.611111 Tz (cancer, ) Tj 2.236111 0 Td 50 Tz (thyroid ) Tj 2.294444 0 Td 53.148148 Tz (carcinoma, ) Tj 3.422222 0 Td 60.185185 Tz (Hodgkin ) Tj 51.428571 0 0 51.428571 0 1951.067416 Tm 25.297222 0 Td 60.493827 Tz (lymphoma, ) Tj 3.480556 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 49.016204 Tz (invasive ) Tj 2.527778 0 Td 52.391975 Tz (glioblastoma ) Tj 3.966667 0 Td 51.557239 Tz (multiforme. ) Tj 51.428571 0 0 51.428571 0 1909.230179 Tm 26.036111 0 Td 37.268519 Tz (It ) Tj 0.563889 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 50.231481 Tz (thus ) Tj 1.361111 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 54.444444 Tz (determined ) Tj 3.402778 0 Td 45.37037 Tz (that ) Tj 1.244444 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 44.907407 Tz (ability ) Tj 2.022222 0 Td 46.990741 Tz (to ) Tj 0.7 0 Td 49.016204 Tz (prevent, ) Tj 2.488889 0 Td 53.472222 Tz (or ) Tj 0.758333 0 Td 45.37037 Tz (at ) Tj 51.428571 0 0 51.428571 0 1868.751269 Tm 25.297222 0 Td 44.722222 Tz (least ) Tj 1.613889 0 Td 49.537037 Tz (reduce, ) Tj 2.313889 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 61.574074 Tz (amount ) Tj 2.45 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 71.296296 Tz (LPA ) Tj 1.555556 0 Td 50.771605 Tz (within ) Tj 2.061111 0 Td 66.111111 Tz (human ) Tj 2.236111 0 Td 59.953704 Tz (body ) Tj 1.691667 0 Td 51.851852 Tz (holds ) Tj 51.428571 0 0 51.428571 0 1833.089987 Tm 25.297222 0 Td 47.962963 Tz (great ) Tj 1.711111 0 Td 56.018519 Tz (promise ) Tj 2.625 0 Td 38.888889 Tz (at, ) Tj 0.991667 0 Td 47.170782 Tz (likewise, ) Tj 2.838889 0 Td 50.05144 Tz (reducing, ) Tj 2.994444 0 Td 42.12963 Tz (if ) Tj 0.719444 0 Td 50.771605 Tz (not ) Tj 1.147222 0 Td 49.494949 Tz (preventing, ) Tj 3.538889 0 Td 50.771605 Tz (the ) Tj 48.571429 0 0 48.571429 0 1791 Tm 26.785294 0 Td 54.901961 Tz (onset ) Tj 1.770588 0 Td 56.617647 Tz (of ) Tj 0.761765 0 Td 49.509804 Tz (certain ) Tj 2.223529 0 Td 51.041667 Tz (cancers. ) Tj 2.635294 0 Td 37.745098 Tz (It ) Tj 0.555882 0 Td 57.189542 Tz (has ) Tj 1.152941 0 Td 61.764706 Tz (been ) Tj 1.585294 0 Td 53.186275 Tz (theorized,as ) Tj 3.973529 0 Td 56.960784 Tz (noted ) Tj 1.832353 0 Td 54.901961 Tz (above, ) Tj 51.428571 0 0 51.428571 0 1750.622378 Tm 25.277778 0 Td 46.990741 Tz (that ) Tj 1.205556 0 Td 50.05144 Tz (autotaxin ) Tj 2.858333 0 Td 50.356125 Tz (modifications ) Tj 4.063889 0 Td 68.055556 Tz (may ) Tj 1.341667 0 Td 51.388889 Tz (prevent ) Tj 2.236111 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 50.673401 Tz (undesirable ) Tj 3.461111 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 1713.807169 Tm 25.297222 0 Td 50.925926 Tz (version ) Tj 2.313889 0 Td 57.523148 Tz (from ) Tj 1.594444 0 Td 73.45679 Tz (LPC ) Tj 1.516667 0 Td 43.75 Tz (to ) Tj 0.758333 0 Td 59.953704 Tz (LPA; ) Tj 1.652778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 43.981481 Tz (ability ) Tj 2.061111 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 48.206019 Tz (actually ) Tj 2.508333 0 Td 55.416667 Tz (accomplish ) Tj 51.428571 0 0 51.428571 0 1670.977778 Tm 25.316667 0 Td 54.282407 Tz (Such ) Tj 1.458333 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 45.37037 Tz (result ) Tj 1.769444 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 46.180556 Tz (elusive, ) Tj 2.391667 0 Td 54.282407 Tz (however, ) Tj 2.741667 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 1.477778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 53.472222 Tz (degree ) Tj 52.857143 0 0 52.857143 0 1631.52431 Tm 24.613514 0 Td 50.800801 Tz (necessary ) Tj 3.140541 0 Td 47.297297 Tz (for ) Tj 1.191892 0 Td 45.195195 Tz (effective ) Tj 2.818919 0 Td 49.303849 Tz (broad-scale ) Tj 3.651351 0 Td 42.997543 Tz (utilization ) Tj 3.254054 0 Td 55.18018 Tz (of ) Tj 0.945946 0 Td 53.603604 Tz (such ) Tj 1.683784 0 Td 53.603604 Tz (a ) Tj 51.428571 0 0 51.428571 0 1591.55092 Tm 25.297222 0 Td 55.555556 Tz (method. ) Tj 2.547222 0 Td 66.975309 Tz (Any ) Tj 1.458333 0 Td 50.501543 Tz (modification ) Tj 3.85 0 Td 51.388889 Tz (thereof ) Tj 2.294444 0 Td 58.333333 Tz (must ) Tj 1.575 0 Td 48.148148 Tz (exhibit ) Tj 2.216667 0 Td 56.712963 Tz (an ) Tj 0.875 0 Td 44.444444 Tz (ability ) Tj 2.080556 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 1554.526882 Tm 25.297222 0 Td 45.664983 Tz (drastically ) Tj 3.227778 0 Td 52.932099 Tz (reduce ) Tj 2.061111 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 45.37037 Tz (activity ) Tj 2.333333 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.05144 Tz (autotaxin ) Tj 2.877778 0 Td 53.148148 Tz (while ) Tj 1.75 0 Td 44.722222 Tz (also, ) Tj 1.477778 0 Td 55.092593 Tz (prefer ) Tj 51.428571 0 0 51.428571 0 1516.797297 Tm 25.297222 0 Td 51.851852 Tz (ably ) Tj 1.438889 0 Td 48.935185 Tz (exhibiting ) Tj 3.091667 0 Td 47.800926 Tz (oral ) Tj 1.341667 0 Td 46.234568 Tz (bioavailability ) Tj 4.336111 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 47.314815 Tz (well. ) Tj 40 0 0 40 0 1480 Tm 33.475 0 Td 64.583333 Tz (Past ) Tj 1.975 0 Td 81.25 Tz (work ) Tj 2.375 0 Td 58.333333 Tz (at ) Tj 1.1 0 Td 100 Tz (ATX ) Tj 2.275 0 Td 60 Tz (inhibition ) Tj 4.075 0 Td 68.055556 Tz (has ) Tj 1.7 0 Td 67.1875 Tz (included ) Tj 3.7 0 Td 59.375 Tz (L-histidine. ) Tj 51.428571 0 0 51.428571 0 1435.265306 Tm 25.297222 0 Td 50 Tz (Unfortunately, ) Tj 4.491667 0 Td 51.203704 Tz (millimolar ) Tj 3.286111 0 Td 50.462963 Tz (concentrations ) Tj 4.511111 0 Td 59.143519 Tz (were ) Tj 1.691667 0 Td 50.231481 Tz (required ) Tj 2.663889 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 1397.714976 Tm 25.297222 0 Td 57.253086 Tz (any ) Tj 1.205556 0 Td 44.290123 Tz (efficacy, ) Tj 2.547222 0 Td 51.041667 Tz (and, ) Tj 1.419444 0 Td 61.574074 Tz (more ) Tj 1.633333 0 Td 48.881173 Tz (importantly, ) Tj 3.713889 0 Td 49.421296 Tz (Zinc ) Tj 1.361111 0 Td 45.833333 Tz (sulfate ) Tj 2.080556 0 Td 53.06713 Tz (presence ) Tj 2.722222 0 Td 44.290123 Tz (\(in ) Tj 51.428571 0 0 51.428571 0 1354.53125 Tm 25.316667 0 Td 52.10114 Tz (Submillimolar ) Tj 4.686111 0 Td 49.691358 Tz (concentrations\) ) Tj 5.133333 0 Td 52.932099 Tz (suggested ) Tj 3.461111 0 Td 58.333333 Tz (an ) Tj 1.341667 0 Td 47.314815 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 1315.384049 Tm 25.297222 0 Td 60.853909 Tz (mechanism ) Tj 3.538889 0 Td 50.771605 Tz (involving ) Tj 2.975 0 Td 46.843434 Tz (interaction ) Tj 3.325 0 Td 53.472222 Tz (with ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 60.493827 Tz (two ) Tj 1.341667 0 Td 48.070988 Tz (native ) Tj 1.944444 0 Td 48.070988 Tz (active ) Tj 51.428571 0 0 51.428571 0 1275.287129 Tm 25.316667 0 Td 41.319444 Tz (site ) Tj 1.225 0 Td 52.5 Tz (metal ) Tj 1.827778 0 Td 48.611111 Tz (ions ) Tj 1.419444 0 Td 45.775463 Tz (thereof. ) Tj 2.430556 0 Td 55.740741 Tz (Other ) Tj 1.866667 0 Td 46.8107 Tz (potential ) Tj 2.702778 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.342593 Tz (inhibitors ) Tj 2.975 0 Td 57.523148 Tz (have ) Tj 51.428571 0 0 51.428571 0 1239.962515 Tm 25.297222 0 Td 52.256944 Tz (included ) Tj 2.761111 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 52.256944 Tz (products ) Tj 2.741667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 56.837607 Tz (ATX-catalyzed ) Tj 4.627778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.266667 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 71.296296 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 1199.484076 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.4 0 Td 51.851852 Tz (sphingosyl ) Tj 3.480556 0 Td 53.376906 Tz (phosphorylcholine ) Tj 5.794444 0 Td 52.932099 Tz (\(SPC\), ) Tj 2.294444 0 Td 61.574074 Tz (LPA, ) Tj 1.827778 0 Td 58.333333 Tz (and ) Tj 1.419444 0 Td 51.041667 Tz (S1P. ) Tj 51.428571 0 0 51.428571 0 1159.334132 Tm 25.297222 0 Td 46.118234 Tz (respectively. ) Tj 3.791667 0 Td 46.990741 Tz (Inhibition ) Tj 2.955556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 76.697531 Tz (ATX ) Tj 1.497222 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 70.216049 Tz (LPA ) Tj 1.419444 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 65.895062 Tz (S1P ) Tj 1.322222 0 Td 51.041667 Tz (suggests ) Tj 2.586111 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 1119.168894 Tm 25.297222 0 Td 53.240741 Tz (product ) Tj 2.430556 0 Td 55.497685 Tz (feedback ) Tj 2.858333 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 66.975309 Tz (may ) Tj 1.419444 0 Td 49.259259 Tz (contribute ) Tj 3.169444 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 48.287037 Tz (regulation ) Tj 3.130556 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1079.835443 Tm 25.297222 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 50.231481 Tz (function ) Tj 2.702778 0 Td 45.37037 Tz (in ) Tj 0.875 0 Td 46.018519 Tz (vivo. ) Tj 1.730556 0 Td 50.555556 Tz (Previously ) Tj 3.344444 0 Td 50.231481 Tz (reported ) Tj 2.663889 0 Td 76.697531 Tz (ATX ) Tj 1.672222 0 Td 46.342593 Tz (inhibitors ) Tj 51.428571 0 0 51.428571 0 1039.178266 Tm 25.316667 0 Td 50.555556 Tz (share ) Tj 1.711111 0 Td 48.148148 Tz (several ) Tj 2.255556 0 Td 70.216049 Tz (common ) Tj 2.741667 0 Td 45.694444 Tz (structural ) Tj 2.955556 0 Td 45.730453 Tz (features, ) Tj 2.702778 0 Td 50.411523 Tz (including ) Tj 2.936111 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 67.24537 Tz (phos ) Tj 51.428571 0 0 51.428571 0 1004.443084 Tm 25.297222 0 Td 48.611111 Tz (phate, ) Tj 2.061111 0 Td 50.925926 Tz (thiophosphate, ) Tj 4.627778 0 Td 53.472222 Tz (or ) Tj 0.933333 0 Td 55.976431 Tz (phosphonate ) Tj 4.005556 0 Td 56.893004 Tz (headgroup ) Tj 3.402778 0 Td 51.041667 Tz (attached ) Tj 51.428571 0 0 51.428571 0 958.761905 Tm 25.297222 0 Td 46.990741 Tz (either ) Tj 1.866667 0 Td 53.472222 Tz (with ) Tj 1.516667 0 Td 53.472222 Tz (or ) Tj 0.836111 0 Td 53.240741 Tz (without ) Tj 2.45 0 Td 51.851852 Tz (a ) Tj 0.544444 0 Td 47.530864 Tz (linker ) Tj 1.905556 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 56.712963 Tz (an ) Tj 0.913889 0 Td 47.962963 Tz (alkyl ) Tj 1.652778 0 Td 49.151235 Tz (chain, ) Tj 2.002778 0 Td 58.333333 Tz (which ) Tj 1.963889 0 Td 58.333333 Tz (can ) Tj 51.428571 0 0 51.428571 0 920.566295 Tm 25.297222 0 Td 52.662037 Tz (vary ) Tj 1.458333 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 47.222222 Tz (overall ) Tj 2.158333 0 Td 50.231481 Tz (length ) Tj 2.002778 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 55.092593 Tz (can ) Tj 1.166667 0 Td 58.333333 Tz (be ) Tj 0.855556 0 Td 47.530864 Tz (either ) Tj 1.866667 0 Td 48.611111 Tz (Saturated ) Tj 2.8 0 Td 53.472222 Tz (or ) Tj 0.777778 0 Td 56.481481 Tz (unsatur ) Tj 51.428571 0 0 51.428571 0 880.665463 Tm 25.297222 0 Td 44.722222 Tz (ated. ) Tj 1.594444 0 Td 56.30787 Tz (However, ) Tj 2.916667 0 Td 49.907407 Tz (these ) Tj 1.633333 0 Td 62.294239 Tz (compounds ) Tj 3.538889 0 Td 53.472222 Tz (both ) Tj 1.477778 0 Td 51.041667 Tz (lack ) Tj 1.380556 0 Td 46.843434 Tz (substantial ) Tj 3.266667 0 Td 55.092593 Tz (struc ) Tj 51.428571 0 0 51.428571 0 844.098039 Tm 25.277778 0 Td 44.074074 Tz (tural ) Tj 1.516667 0 Td 46.090535 Tz (diversity ) Tj 2.663889 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 38.888889 Tz (fail ) Tj 1.127778 0 Td 42.12963 Tz (to ) Tj 0.719444 0 Td 59.143519 Tz (meet ) Tj 1.575 0 Td 48.611111 Tz (Lipinskis ) Tj 3.091667 0 Td 50.411523 Tz (empirical ) Tj 2.916667 0 Td 46.018519 Tz (rules ) Tj 1.555556 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 802.507463 Tm 25.297222 0 Td 48.881173 Tz (characterize ) Tj 3.733333 0 Td 73.45679 Tz (90% ) Tj 1.555556 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 46.990741 Tz (orally ) Tj 1.905556 0 Td 49.421296 Tz (bioavailable ) Tj 3.791667 0 Td 48.070988 Tz (drugs. ) Tj 2.041667 0 Td 35.648148 Tz (It ) Tj 0.641667 0 Td 38.888889 Tz (is ) Tj 0.680556 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 49.259259 Tz (great ) Tj 51.428571 0 0 51.428571 0 765.340206 Tm 25.297222 0 Td 55.092593 Tz (importance ) Tj 3.636111 0 Td 48.611111 Tz (to ) Tj 0.972222 0 Td 46.990741 Tz (identify ) Tj 2.683333 0 Td 51.851852 Tz (novel ) Tj 2.002778 0 Td 48.611111 Tz (non-lipid ) Tj 3.013889 0 Td 45.694444 Tz (structural ) Tj 3.130556 0 Td 48.148148 Tz (classes ) Tj 51.428571 0 0 51.428571 0 724.355152 Tm 25.297222 0 Td 53.240741 Tz (capable ) Tj 2.411111 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 46.666667 Tz (inhibiting ) Tj 2.975 0 Td 76.697531 Tz (ATX ) Tj 1.575 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 57.685185 Tz (which ) Tj 1.944444 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 46.990741 Tz (orally ) Tj 1.866667 0 Td 49.421296 Tz (bioavailable ) Tj 40 0 0 40 0 690 Tm 32.5 0 Td 60.416667 Tz (to ) Tj 0.95 0 Td 56.666667 Tz (treat ) Tj 1.925 0 Td 60.119048 Tz (certain ) Tj 2.75 0 Td 76.666667 Tz (tumor ) Tj 2.525 0 Td 57.8125 Tz (classes. ) Tj 51.428571 0 0 51.428571 0 645.564661 Tm 26.036111 0 Td 37.268519 Tz (It ) Tj 0.641667 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 48.971193 Tz (believed, ) Tj 2.838889 0 Td 53.240741 Tz (without ) Tj 2.411111 0 Td 49.537037 Tz (relying ) Tj 2.255556 0 Td 59.953704 Tz (upon ) Tj 1.633333 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 45.775463 Tz (specific ) Tj 2.411111 0 Td 43.75 Tz (scientific ) Tj 51.428571 0 0 51.428571 0 605.445798 Tm 25.277778 0 Td 45.37037 Tz (basis, ) Tj 1.827778 0 Td 45.37037 Tz (that ) Tj 1.244444 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 51.851852 Tz (lack ) Tj 1.380556 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 46.090535 Tz (diversity ) Tj 2.663889 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 49.826389 Tz (reported ) Tj 2.488889 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 44.781145 Tz (inhibitors, ) Tj 3.111111 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 563.722444 Tm 25.297222 0 Td 53.796296 Tz (noted ) Tj 1.886111 0 Td 52.391975 Tz (above, ) Tj 2.158333 0 Td 38.888889 Tz (is ) Tj 0.758333 0 Td 50.231481 Tz (due, ) Tj 1.497222 0 Td 43.75 Tz (in ) Tj 0.797222 0 Td 44.074074 Tz (part, ) Tj 1.575 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 51.851852 Tz (lack ) Tj 1.497222 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 58.333333 Tz (a ) Tj 0.602778 0 Td 49.85755 Tz (characterized ) Tj 51.428571 0 0 51.428571 0 525.342355 Tm 25.277778 0 Td 51.66122 Tz (three-dimensional ) Tj 5.813889 0 Td 47.170782 Tz (structure ) Tj 3.072222 0 Td 59.953704 Tz (of ) Tj 1.166667 0 Td 48.611111 Tz (the ) Tj 1.419444 0 Td 57.407407 Tz (enzyme. ) Tj 2.975 0 Td 62.654321 Tz (The ) Tj 1.613889 0 Td 78.858025 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 485.429698 Tm 25.316667 0 Td 55.092593 Tz (sequence ) Tj 2.955556 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 55.092593 Tz (over ) Tj 1.575 0 Td 61.574074 Tz (860 ) Tj 1.4 0 Td 59.62963 Tz (amino ) Tj 2.1 0 Td 49.907407 Tz (acids ) Tj 1.808333 0 Td 38.888889 Tz (is ) Tj 0.777778 0 Td 51.851852 Tz (divided ) Tj 2.488889 0 Td 45.37037 Tz (into ) Tj 1.438889 0 Td 47.685185 Tz (several ) Tj 51.428571 0 0 51.428571 0 449.093023 Tm 25.297222 0 Td 55.092593 Tz (domains, ) Tj 2.877778 0 Td 50.771605 Tz (including ) Tj 2.955556 0 Td 51.851852 Tz (a ) Tj 0.583333 0 Td 46.296296 Tz (central ) Tj 2.177778 0 Td 45.37037 Tz (catalytic ) Tj 2.683333 0 Td 60.493827 Tz (domain ) Tj 2.430556 0 Td 61.168981 Tz (composed ) Tj 3.169444 0 Td 56.712963 Tz (of ) Tj 40 0 0 40 0 413 Tm 32.525 0 Td 70 Tz (about ) Tj 2.325 0 Td 81.944444 Tz (400 ) Tj 1.725 0 Td 76.666667 Tz (amino ) Tj 2.6 0 Td 59.027778 Tz (acids. ) Tj 2.425 0 Td 97.222222 Tz (ATX ) Tj 2.05 0 Td 52.083333 Tz (is ) Tj 0.925 0 Td 70.833333 Tz (a ) Tj 0.725 0 Td 84.722222 Tz (member ) Tj 3.3 0 Td 77.083333 Tz (of ) Tj 1.075 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 65 Tz (nucleotide ) Tj 51.428571 0 0 51.428571 0 371.944186 Tm 25.297222 0 Td 52.637486 Tz (pyrophosphatase/phosphodiesterase ) Tj 10.558333 0 Td 60.925926 Tz (\(NPP\) ) Tj 1.983333 0 Td 47.685185 Tz (family, ) Tj 2.138889 0 Td 51.851852 Tz (as ) Tj 0.777778 0 Td 51.041667 Tz (well ) Tj 1.380556 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 331.681293 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 48.611111 Tz (alkaline ) Tj 2.45 0 Td 53.914141 Tz (phosphatase ) Tj 3.694444 0 Td 49.421296 Tz (Superfamily. ) Tj 3.694444 0 Td 50.434028 Tz (Crystallographic ) Tj 4.997222 0 Td 54.444444 Tz (struc ) Tj 51.428571 0 0 51.428571 0 290.487923 Tm 25.277778 0 Td 47.314815 Tz (tures ) Tj 1.691667 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 48.148148 Tz (several ) Tj 2.275 0 Td 48.206019 Tz (alkaline ) Tj 2.508333 0 Td 54.503367 Tz (phosphatase ) Tj 3.85 0 Td 51.851852 Tz (Superfamily ) Tj 3.694444 0 Td 62.962963 Tz (members ) Tj 51.428571 0 0 51.428571 0 248.016688 Tm 25.277778 0 Td 57.523148 Tz (have ) Tj 1.672222 0 Td 57.523148 Tz (been ) Tj 1.730556 0 Td 48.251029 Tz (available ) Tj 2.955556 0 Td 46.450617 Tz (for ) Tj 1.166667 0 Td 51.041667 Tz (decades. ) Tj 2.780556 0 Td 58.333333 Tz (These ) Tj 2.080556 0 Td 45.833333 Tz (crystal ) Tj 2.275 0 Td 46.990741 Tz (structures ) Tj 40 0 0 40 0 216 Tm 32.55 0 Td 77.083333 Tz (show ) Tj 2.175 0 Td 70 Tz (remarkable ) Tj 4.4 0 Td 58.75 Tz (structural ) Tj 3.775 0 Td 65.625 Tz (conservation ) Tj 5 0 Td 56.25 Tz (in ) Tj 0.925 0 Td 66.666667 Tz (a ) Tj 0.65 0 Td 66.666667 Tz (small ) Tj 2.225 0 Td 66.666667 Tz (core ) Tj 1.875 0 Td 77.777778 Tz (Sur ) Tj 51.428571 0 0 51.428571 0 172.795839 Tm 25.297222 0 Td 54.6875 Tz (rounding ) Tj 2.975 0 Td 49.691358 Tz (the ) Tj 1.263889 0 Td 45.010288 Tz (catalytic ) Tj 2.780556 0 Td 39.537037 Tz (site, ) Tj 1.536111 0 Td 51.851852 Tz (but ) Tj 1.283333 0 Td 50.106838 Tz (unfortunately ) Tj 4.258333 0 Td 61.574074 Tz (show ) Tj 1.866667 0 Td 83.179012 Tz (com ) Tj ET Q endstream endobj 120 0 obj << /Length 1 >> stream q endstream endobj 121 0 obj << /Length 18549 >> 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Tz (with ) Tj 1.9 0 Td 100 Tz (ATX ) Tj 2.1 0 Td 69.791667 Tz (does ) Tj 1.95 0 Td 66.666667 Tz (not ) Tj 1.4 0 Td 72.916667 Tz (exceed ) Tj 2.975 0 Td 87.5 Tz (14% ) Tj 1.85 0 Td 76.388889 Tz (and ) Tj 1.625 0 Td 50 Tz (is ) Tj 0.875 0 Td 62.5 Tz (therefore ) Tj 3.65 0 Td 57.986111 Tz (insufficient ) Tj 51.428571 0 0 51.428571 0 2793.692924 Tm 6.358333 0 Td 48.611111 Tz (for ) Tj 1.166667 0 Td 51.203704 Tz (generation ) Tj 3.422222 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 58.333333 Tz (a ) Tj 0.661111 0 Td 53.472222 Tz (high ) Tj 1.633333 0 Td 47.685185 Tz (quality ) Tj 2.333333 0 Td 61.168981 Tz (homology ) Tj 3.325 0 Td 58.981481 Tz (model ) Tj 2.119444 0 Td 43.75 Tz (in ) Tj 0.855556 0 Td 59.41358 Tz (any ) Tj 51.428571 0 0 51.428571 0 2751.540284 Tm 6.358333 0 Td 50.771605 Tz (region ) Tj 1.983333 0 Td 50.462963 Tz (outside ) Tj 2.255556 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 53.596866 Tz (approximately ) Tj 4.394444 0 Td 58.333333 Tz (100 ) Tj 1.186111 0 Td 59.62963 Tz (amino 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Tm 6.358333 0 Td 52.662037 Tz (core ) Tj 1.361111 0 Td 60.493827 Tz (domain ) Tj 2.313889 0 Td 53.240741 Tz (enabled ) Tj 2.372222 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 56.565657 Tz (development ) Tj 3.830556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 45.046296 Tz (structural ) Tj 2.877778 0 Td 59.62963 Tz (model ) Tj 1.905556 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2583.666667 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 45.37037 Tz (catalytic ) Tj 2.644444 0 Td 59.953704 Tz (domain ) Tj 2.333333 0 Td 45.37037 Tz (that ) Tj 1.263889 0 Td 66.975309 Tz (may ) Tj 1.380556 0 Td 55.092593 Tz (prove ) Tj 1.827778 0 Td 48.611111 Tz (useful ) Tj 1.944444 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 51.49177 Tz (structure ) Tj 51.428571 0 0 51.428571 0 2545.368113 Tm 6.338889 0 Td 56.388889 Tz (based ) Tj 1.808333 0 Td 55.902778 Tz (drug ) Tj 1.477778 0 Td 49.074074 Tz (design. ) Tj 2.177778 0 Td 57.118056 Tz (Although ) Tj 2.858333 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 45.959596 Tz (significant ) Tj 3.169444 0 Td 55.902778 Tz (improvement, ) Tj 4.180556 0 Td 55.902778 Tz (Such ) Tj 51.428571 0 0 51.428571 0 2500.915094 Tm 6.358333 0 Td 55.092593 Tz (a ) Tj 0.427778 0 Td 61.574074 Tz (homology ) Tj 3.111111 0 Td 59.62963 Tz (model ) Tj 1.925 0 Td 59.143519 Tz (must ) Tj 1.516667 0 Td 58.333333 Tz (be ) Tj 0.797222 0 Td 51.388889 Tz (applied ) Tj 2.294444 0 Td 49.259259 Tz (cautiously ) Tj 3.091667 0 Td 48.611111 Tz (as ) Tj 0.719444 0 Td 54.503367 Tz (involvement ) Tj 51.428571 0 0 51.428571 0 2457.184116 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 52.932099 Tz (the ) Tj 1.127778 0 Td 49.583333 Tz (c-terminal ) Tj 3.208333 0 Td 48.860399 Tz (nuclease-like ) Tj 4.005556 0 Td 59.953704 Tz (domain ) Tj 2.372222 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 48.251029 Tz (Substrate ) Tj 2.819444 0 Td 56.944444 Tz (recogni ) Tj 51.428571 0 0 51.428571 0 2416.359223 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.302778 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 56.712963 Tz (been ) Tj 1.555556 0 Td 52.932099 Tz (suggested ) Tj 3.033333 0 Td 57.523148 Tz (from ) Tj 1.575 0 Td 47.222222 Tz (studies ) Tj 2.138889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 75.617284 Tz (NPP ) Tj 1.516667 0 Td 51.851852 Tz (family ) Tj 2.061111 0 Td 66.435185 Tz (domain ) Tj 51.428571 0 0 51.428571 0 2377.688645 Tm 6.377778 0 Td 57.928241 Tz (Swapping ) Tj 2.994444 0 Td 51.131687 Tz (chimeras. ) Tj 3.033333 0 Td 46.990741 Tz (In ) Tj 0.777778 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 48.611111 Tz (event, ) Tj 1.963889 0 Td 50.555556 Tz (these ) Tj 1.691667 0 Td 51.203704 Tz (previously ) Tj 3.325 0 Td 50.636574 Tz (reported ) Tj 51.428571 0 0 51.428571 0 2334.150617 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.018519 Tz (inhibitors ) Tj 2.975 0 Td 49.691358 Tz (are ) Tj 1.088889 0 Td 52.777778 Tz (analogs ) Tj 2.430556 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 60.763889 Tz (LPA, ) Tj 1.672222 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 51.103989 Tz (phospholipid, ) Tj 4.161111 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 50.771605 Tz (are ) Tj 51.428571 0 0 51.428571 0 2294.42654 Tm 6.358333 0 Td 61.574074 Tz (more ) Tj 1.613889 0 Td 55.387205 Tz (hydrophobic ) Tj 3.811111 0 Td 51.041667 Tz (than ) Tj 1.380556 0 Td 37.268519 Tz (is ) Tj 0.583333 0 Td 46.759259 Tz (typical ) Tj 2.080556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 47.530864 Tz (orally ) Tj 1.827778 0 Td 48.881173 Tz (bioavailable ) Tj 3.655556 0 Td 48.611111 Tz (drugs, ) Tj 51.428571 0 0 51.428571 0 2253.631879 Tm 6.338889 0 Td 52.314815 Tz (thereby ) Tj 2.411111 0 Td 48.206019 Tz (creating ) Tj 2.488889 0 Td 56.30787 Tz (problems ) Tj 2.897222 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 46.180556 Tz (that ) Tj 1.283333 0 Td 45.37037 Tz (area. ) Tj 51.428571 0 0 51.428571 0 2195.451815 Tm 7.097222 0 Td 66.435185 Tz (As ) Tj 0.952778 0 Td 48.611111 Tz (such, ) Tj 1.633333 0 Td 48.611111 Tz (there ) Tj 1.575 0 Td 45.37037 Tz (exists ) Tj 1.769444 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 45.37037 Tz (definitive ) Tj 2.838889 0 Td 51.041667 Tz (lack ) Tj 1.341667 0 Td 46.990741 Tz (in ) Tj 0.7 0 Td 52.211934 Tz (providing ) Tj 2.936111 0 Td 46.8107 Tz (effective ) Tj 51.428571 0 0 51.428571 0 2150 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 46.666667 Tz (inhibition ) Tj 3.111111 0 Td 47.530864 Tz (\(or ) Tj 1.108333 0 Td 46.616809 Tz (inactivation\) ) Tj 3.927778 0 Td 50.231481 Tz (within ) Tj 2.1 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 49.537037 Tz (current ) Tj 2.333333 0 Td 68.055556 Tz (knowl ) Tj 51.428571 0 0 51.428571 0 2111.058537 Tm 6.358333 0 Td 57.523148 Tz (edge ) Tj 1.516667 0 Td 55.092593 Tz (base ) Tj 1.497222 0 Td 43.75 Tz (in ) Tj 0.719444 0 Td 42.939815 Tz (this ) Tj 1.186111 0 Td 47.314815 Tz (area, ) Tj 1.555556 0 Td 46.720679 Tz (particularly ) Tj 3.538889 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 32.407407 Tz (it ) Tj 0.563889 0 Td 53.472222 Tz (concerns ) Tj 2.741667 0 Td 61.934156 Tz (compounds ) Tj 51.428571 0 0 51.428571 0 2063.621266 Tm 6.338889 0 Td 46.990741 Tz (that ) Tj 1.244444 0 Td 51.851852 Tz (not ) Tj 1.05 0 Td 52.662037 Tz (only ) Tj 1.380556 0 Td 48.148148 Tz (exhibit ) Tj 2.1 0 Td 77.777778 Tz (ATX ) Tj 1.536111 0 Td 45.37037 Tz (inhibition, ) Tj 3.091667 0 Td 50.771605 Tz (but ) Tj 1.05 0 Td 46.990741 Tz (also ) Tj 1.302778 0 Td 58.333333 Tz (meet ) Tj 1.516667 0 Td 47.222222 Tz (certain ) Tj 2.1 0 Td 46.180556 Tz (oral ) Tj 51.428571 0 0 51.428571 0 2025.099617 Tm 6.338889 0 Td 46.450617 Tz (bioavailability ) Tj 4.627778 0 Td 52.662037 Tz (requirements ) Tj 4.238889 0 Td 46.450617 Tz (\(as ) Tj 1.302778 0 Td 57.928241 Tz (measured ) Tj 3.188889 0 Td 59.953704 Tz (by ) Tj 1.205556 0 Td 48.611111 Tz (Lipinski's ) Tj 51.428571 0 0 51.428571 0 1976 Tm 6.358333 0 Td 43.518519 Tz (rules\). ) Tj 2.022222 0 Td 72.916667 Tz (No ) Tj 1.069444 0 Td 55.092593 Tz (such ) Tj 1.555556 0 Td 55.902778 Tz (need ) Tj 1.497222 0 Td 54.012346 Tz (has ) Tj 1.166667 0 Td 56.712963 Tz (been ) Tj 1.594444 0 Td 59.41358 Tz (met ) Tj 1.263889 0 Td 42.777778 Tz (until ) Tj 1.516667 0 Td 55.092593 Tz (now. ) Tj 51.428571 0 0 51.428571 0 1873.937765 Tm 7.738889 0 Td 57.037037 Tz (Advantages ) Tj 3.577778 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 50.555556 Tz (Brief ) Tj 1.652778 0 Td 50.673401 Tz (Description ) Tj 3.519444 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 51.851852 Tz (the ) Tj 1.108333 0 Td 50.771605 Tz (Invention ) Tj 51.428571 0 0 51.428571 0 1773.921773 Tm 7.116667 0 Td 35.648148 Tz (It ) Tj 0.622222 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 50.231481 Tz (thus ) Tj 1.419444 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 54.73251 Tz (advantage ) Tj 3.130556 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 50.462963 Tz (present ) Tj 2.333333 0 Td 49.331276 Tz (invention ) Tj 2.877778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 53.240741 Tz (provide ) Tj 51.428571 0 0 51.428571 0 1730.377358 Tm 6.358333 0 Td 45.775463 Tz (reliable ) Tj 2.313889 0 Td 50.05144 Tz (autotaxin ) Tj 2.858333 0 Td 46.720679 Tz (inactivators ) Tj 3.519444 0 Td 47.530864 Tz (for ) Tj 0.952778 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 55.555556 Tz (purpose ) Tj 2.488889 0 Td 55.092593 Tz (of ) Tj 0.719444 0 Td 53.472222 Tz (reducing ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1689.115942 Tm 6.358333 0 Td 52.5 Tz (conversion ) Tj 3.286111 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 73.45679 Tz (LPC ) Tj 1.458333 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 71.296296 Tz (LPA ) Tj 1.438889 0 Td 53.240741 Tz (through ) Tj 2.391667 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 44.191919 Tz (utilization ) Tj 3.052778 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 48.148148 Tz (readily ) Tj 52.857143 0 0 52.857143 0 1649.302326 Tm 6.186486 0 Td 46.946947 Tz (available ) Tj 2.62973 0 Td 57.807808 Tz (and ) Tj 1.135135 0 Td 45.720721 Tz (easily ) Tj 1.759459 0 Td 55.18018 Tz (produced ) Tj 2.762162 0 Td 62.274775 Tz (compound ) Tj 3.102703 0 Td 46.246246 Tz (\(or ) Tj 0.945946 0 Td 58.333333 Tz (compounds\) ) Tj 3.594595 0 Td 44.932432 Tz (that ) Tj 51.428571 0 0 51.428571 0 1605.936842 Tm 6.358333 0 Td 55.092593 Tz (does ) Tj 1.672222 0 Td 49.691358 Tz (not ) Tj 1.166667 0 Td 56.712963 Tz (pose ) Tj 1.652778 0 Td 57.253086 Tz (any ) Tj 1.361111 0 Td 45.959596 Tz (significant ) Tj 3.286111 0 Td 49.691358 Tz (health ) Tj 2.1 0 Td 45.37037 Tz (risks ) Tj 1.672222 0 Td 59.41358 Tz (and ) Tj 1.361111 0 Td 48.148148 Tz (exhibit ) Tj 2.313889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1566.333333 Tm 6.358333 0 Td 52.211934 Tz (necessary ) Tj 3.033333 0 Td 46.990741 Tz (oral ) Tj 1.322222 0 Td 46.450617 Tz (bioavailability ) Tj 4.413889 0 Td 50.854701 Tz (requirements. ) Tj 4.161111 0 Td 56.944444 Tz (Another ) Tj 2.566667 0 Td 65.462963 Tz (advan ) Tj 51.428571 0 0 51.428571 0 1522.46875 Tm 6.338889 0 Td 51.851852 Tz (tage ) Tj 1.516667 0 Td 40.509259 Tz (is ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 44.444444 Tz (ability ) Tj 2.158333 0 Td 48.611111 Tz (for ) Tj 1.127778 0 Td 51.131687 Tz (treatment ) Tj 3.052778 0 Td 52.662037 Tz (with ) Tj 1.575 0 Td 55.092593 Tz (such ) Tj 1.594444 0 Td 62.294239 Tz (compounds ) Tj 3.694444 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 1482.455882 Tm 6.358333 0 Td 53.472222 Tz (cancer ) Tj 2.061111 0 Td 51.527778 Tz (prevention ) Tj 3.286111 0 Td 51.131687 Tz (treatment ) Tj 2.936111 0 Td 51.851852 Tz (regimens. ) Tj 51.428571 0 0 51.428571 0 1428.12766 Tm 7.097222 0 Td 52.121914 Tz (Accordingly, ) Tj 4.083333 0 Td 44.560185 Tz (this ) Tj 1.438889 0 Td 49.331276 Tz (invention ) Tj 3.013889 0 Td 57.449495 Tz (encompasses ) Tj 4.161111 0 Td 55.092593 Tz (a ) Tj 0.7 0 Td 59.41358 Tz (method ) Tj 2.488889 0 Td 48.611111 Tz (for ) Tj 51.428571 0 0 51.428571 0 1386.875622 Tm 6.338889 0 Td 46.990741 Tz (treating ) Tj 2.488889 0 Td 53.292181 Tz (cancerous ) Tj 3.111111 0 Td 56.17284 Tz (tumors ) Tj 2.236111 0 Td 53.703704 Tz (through ) Tj 2.508333 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 48.971193 Tz (ingestion ) Tj 2.877778 0 Td 59.953704 Tz (by ) Tj 0.972222 0 Td 51.851852 Tz (a ) Tj 0.544444 0 Td 45.910494 Tz (target ) Tj 51.428571 0 0 51.428571 0 1344.828902 Tm 6.358333 0 Td 47.685185 Tz (patient ) Tj 2.1 0 Td 48.935185 Tz (exhibiting ) Tj 3.013889 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 53.292181 Tz (cancerous ) Tj 2.975 0 Td 57.613169 Tz (tumorofat ) Tj 3.208333 0 Td 45.37037 Tz (least ) Tj 1.458333 0 Td 59.41358 Tz (one ) Tj 1.147222 0 Td 64.814815 Tz (compound ) Tj 51.428571 0 0 51.428571 0 1301.326034 Tm 6.377778 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 57.523148 Tz (from ) Tj 1.555556 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 56.388889 Tz (group ) Tj 1.866667 0 Td 49.259259 Tz (consisting ) Tj 3.111111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 43.75 Tz (at ) Tj 0.680556 0 Td 44.722222 Tz (least ) Tj 1.477778 0 Td 58.333333 Tz (one ) Tj 1.205556 0 Td 47.530864 Tz (thiourea, ) Tj 2.722222 0 Td 45.37037 Tz (at ) Tj 51.428571 0 0 51.428571 0 1260.837093 Tm 6.358333 0 Td 44.722222 Tz (least ) Tj 1.613889 0 Td 57.253086 Tz (one ) Tj 1.263889 0 Td 50.951646 Tz (diphenyldiazerene, ) Tj 5.736111 0 Td 46.990741 Tz (at ) Tj 0.797222 0 Td 44.722222 Tz (least ) Tj 1.594444 0 Td 58.333333 Tz (one ) Tj 1.283333 0 Td 51.851852 Tz (Xanthene, ) Tj 3.072222 0 Td 45.37037 Tz (at ) Tj 0.777778 0 Td 44.722222 Tz (least ) Tj 51.428571 0 0 51.428571 0 1218.105263 Tm 6.358333 0 Td 59.41358 Tz (one ) Tj 1.361111 0 Td 46.990741 Tz (isoindole, ) Tj 3.091667 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 57.253086 Tz (any ) Tj 1.361111 0 Td 51.851852 Tz (mixtures ) Tj 2.761111 0 Td 46.585648 Tz (thereof. ) Tj 2.566667 0 Td 48.611111 Tz (In ) Tj 0.855556 0 Td 44.781145 Tz (particular, ) Tj 3.247222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1177.971014 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 58.333333 Tz (from ) Tj 1.555556 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 57.037037 Tz (group ) Tj 1.905556 0 Td 48.935185 Tz (consisting ) Tj 3.091667 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 51.428571 0 0 51.428571 0 1137.191781 Tm 6.358333 0 Td 59.41358 Tz (one ) Tj 1.205556 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 49.583333 Tz (following: ) Tj 31.428571 0 0 31.428571 0 579 Tm 23.036364 0 Td 76.515152 Tz (7905958 ) Tj 31.428571 0 0 31.428571 0 539 Tm 13.681818 0 Td 111.363636 Tz (OH ) Tj 21.254545 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 496.166667 Tm 11.295455 0 Td 111.363636 Tz (O ) Tj 6.554545 0 Td 111.363636 Tz (O ) Tj 6.459091 0 Td 111.363636 Tz (O ) Tj 6.490909 0 Td 111.363636 Tz (O ) Tj 6.554545 0 Td 111.363636 Tz (OH ) Tj 230 0 0 230 0 344 Tm 2.747826 0 Td 85.748792 Tz (oo: ) Tj 31.428571 0 0 31.428571 0 322.223301 Tm 10.690909 0 Td 106.060606 Tz (HO ) Tj 7.159091 0 Td 111.363636 Tz (O ) Tj 12.95 0 Td 111.363636 Tz (O ) Tj 6.554545 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 277 Tm 13.681818 0 Td 111.363636 Tz (O ) Tj 20.65 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 226 Tm 23.418182 0 Td 77.272727 Tz (5186522 ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 192.857143 0 0 192.857143 0 1700 Tm 6.777037 0 Td 31.111111 Tz (r ) Tj 31.428571 0 0 31.428571 0 1672 Tm 44.672727 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1467 Tm 48.745455 0 Td 111.363636 Tz (O ) Tj 14.063636 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 1380 Tm 46.613636 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 1350 Tm 56.413636 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 1253 Tm 56.254545 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1234 Tm 41.745455 0 Td 98.106061 Tz (HO ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.775 0 Td 77.777778 Tz (4 ) Tj 40 0 0 40 0 2913 Tm 41.825 0 Td 66.666667 Tz (-continued ) Tj 267.142857 0 0 267.142857 0 2702 Tm 6.734225 0 Td 72.162805 Tz (COO ) Tj 31.428571 0 0 31.428571 0 2186 Tm 54.027273 0 Td 76.515152 Tz (7839888 ) Tj 434.285714 0 0 434.285714 0 1806 Tm 3.532237 0 Td 46.436404 Tz (are: ) Tj 31.428571 0 0 31.428571 0 1623 Tm 54.409091 0 Td 76.515152 Tz (5761473 ) Tj 31.428571 0 0 31.428571 0 1095 Tm 53.963636 0 Td 76.515152 Tz (5564949 ) Tj 31.428571 0 0 31.428571 0 1005 Tm 55.268182 0 Td 111.363636 Tz (O ) Tj 6.459091 0 Td 111.363636 Tz (O ) Tj 31.428571 0 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Tz (O ) Tj 31.428571 0 0 31.428571 0 2785 Tm 21.572727 0 Td 111.363636 Tz (O ) Tj 55.357143 0 0 55.357143 0 2700.468599 Tm 11.651613 0 Td 221.290323 Tz (1- ) Tj 2.727742 0 Td 42.150538 Tz (S ) Tj 2.023226 0 Td 69.247312 Tz (N ) Tj 2.095484 0 Td 69.247312 Tz (N ) Tj 36.190476 0 0 36.190476 0 2687.966292 Tm 17.103947 0 Td 105.921053 Tz (N ) Tj 6.852632 0 Td 151.973684 Tz (2 ) Tj 3.205263 0 Td 151.973684 Tz (2 ) Tj 31.428571 0 0 31.428571 0 2663 Tm 19.790909 0 Td 106.060606 Tz (H ) Tj 40 0 0 40 0 2608.041096 Tm 21.25 0 Td 95.833333 Tz (N ) Tj 3.325 0 Td 208.333333 Tz (N ) Tj 83.571429 0 0 83.571429 0 2525.179104 Tm 9.584615 0 Td 91.737892 Tz (r ) Tj 1.280342 0 Td 41.880342 Tz (O ) Tj 31.428571 0 0 31.428571 0 2470 Tm 23.036364 0 Td 66.287879 Tz (79.21385 ) Tj 31.428571 0 0 31.428571 0 2433 Tm 12.377273 0 Td 111.363636 Tz (OH ) Tj 13.395455 0 Td 111.363636 Tz (O ) Tj 123.809524 0 0 123.809524 0 2270.276316 Tm 2.713846 0 Td 28.269231 Tz (O ) Tj 2.657308 0 Td 138.653846 Tz (O ) Tj 1.688077 0 Td 140 Tz (O ) Tj 31.428571 0 0 31.428571 0 2253.5 Tm 19.090909 0 Td 111.363636 Tz (O ) Tj 15.018182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2185 Tm 31.468182 0 Td 121.969697 Tz (N ) Tj 109.52381 0 0 109.52381 0 2106.96 Tm 8.080435 0 Td 31.956522 Tz (O ) Tj 1.89 0 Td 41.086957 Tz (\( ) Tj 0.84 0 Td 41.086957 Tz (\) ) Tj 31.428571 0 0 31.428571 0 1974 Tm 23.195455 0 Td 77.272727 Tz (5210574 ) Tj 51.428571 0 0 51.428571 0 1856.714994 Tm 7.097222 0 Td 57.685185 Tz (These ) Tj 1.847222 0 Td 62.294239 Tz (compounds ) Tj 3.519444 0 Td 53.148148 Tz (noted ) Tj 1.711111 0 Td 57.685185 Tz (above ) Tj 1.866667 0 Td 48.148148 Tz (exhibit ) Tj 2.119444 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 50.05144 Tz (reduction ) Tj 2.858333 0 Td 46.990741 Tz (in ) Tj 0.661111 0 Td 90.740741 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 1815.269377 Tm 6.358333 0 Td 51.131687 Tz (catalyzed ) Tj 3.033333 0 Td 56.712963 Tz (FS-3 ) Tj 1.633333 0 Td 50.555556 Tz (hydrolysis ) Tj 3.286111 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 45.910494 Tz (target ) Tj 1.905556 0 Td 58.981481 Tz (tumor ) Tj 1.983333 0 Td 44.722222 Tz (cells ) Tj 1.594444 0 Td 59.953704 Tz (by ) Tj 0.991667 0 Td 72.376543 Tz (50% ) Tj 1.575 0 Td 53.472222 Tz (or ) Tj 51.428571 0 0 51.428571 0 1768 Tm 6.358333 0 Td 61.574074 Tz (more ) Tj 1.652778 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 51.851852 Tz (a ) Tj 0.505556 0 Td 50.605413 Tz (concentration ) Tj 4.122222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.796296 Tz (about ) Tj 1.886111 0 Td 55.092593 Tz (10 ) Tj 0.855556 0 Td 62.654321 Tz (uM. ) Tj 1.322222 0 Td 59.953704 Tz (Such ) Tj 1.633333 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 49.691358 Tz (reduction ) Tj 2.897222 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 1727.613527 Tm 6.358333 0 Td 44.965278 Tz (activity ) Tj 2.313889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.05144 Tz (autotaxin ) Tj 2.877778 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 47.530864 Tz (basically ) Tj 2.741667 0 Td 46.990741 Tz (in ) Tj 0.719444 0 Td 53.796296 Tz (terms ) Tj 1.808333 0 Td 55.092593 Tz (of ) Tj 0.719444 0 Td 47.170782 Tz (potential ) Tj 2.741667 0 Td 59.41358 Tz (conver ) Tj 51.428571 0 0 51.428571 0 1682.875622 Tm 6.377778 0 Td 49.421296 Tz (sion ) Tj 1.4 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 71.296296 Tz (LPC ) Tj 1.536111 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 60.763889 Tz (LPA, ) Tj 1.652778 0 Td 46.720679 Tz (particularly ) Tj 3.616667 0 Td 53.703704 Tz (through ) Tj 2.488889 0 Td 45.37037 Tz (structural ) Tj 2.955556 0 Td 58.873457 Tz (modifi ) Tj 52.857143 0 0 52.857143 0 1640.19656 Tm 6.186486 0 Td 47.747748 Tz (cations ) Tj 2.194595 0 Td 45.720721 Tz (to ) Tj 0.718919 0 Td 50.900901 Tz (prevent ) Tj 2.289189 0 Td 54.654655 Tz (placement ) Tj 3.140541 0 Td 53.603604 Tz (of ) Tj 0.756757 0 Td 49.399399 Tz (the ) Tj 1.097297 0 Td 70.42042 Tz (LPC ) Tj 1.456757 0 Td 62.274775 Tz (compound ) Tj 3.197297 0 Td 44.932432 Tz (into ) Tj 1.267568 0 Td 49.399399 Tz (the ) Tj 51.428571 0 0 51.428571 0 1593.615509 Tm 6.358333 0 Td 48.070988 Tz (active ) Tj 1.905556 0 Td 42.12963 Tz (site ) Tj 1.186111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 53.877315 Tz (modified ) Tj 2.761111 0 Td 49.691358 Tz (autotaxin ) Tj 2.877778 0 Td 57.87037 Tz (enzyme. ) Tj 38.571429 0 0 38.571429 0 1519 Tm 9.92963 0 Td 97.762346 Tz (DETAILED ) Tj 4.977778 0 Td 94.276094 Tz (DESCRIPTION ) Tj 6.533333 0 Td 99.382716 Tz (OF ) Tj 1.4 0 Td 106.584362 Tz (THE ) Tj 2.177778 0 Td 98.902606 Tz (INVENTION ) Tj 38.571429 0 0 38.571429 0 1475 Tm 12.522222 0 Td 116.666667 Tz (AND ) Tj 2.385185 0 Td 101.303155 Tz (PREFERRED ) Tj 5.755556 0 Td 106.453423 Tz (EMBODIMENTS ) Tj 51.428571 0 0 51.428571 0 1382.744304 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.380556 0 Td 51.602564 Tz (determination ) Tj 4.258333 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 53.472222 Tz (proper ) Tj 2.119444 0 Td 77.777778 Tz (ATX ) Tj 1.672222 0 Td 46.666667 Tz (inhibition ) Tj 3.072222 0 Td 61.934156 Tz (compounds ) Tj 51.428571 0 0 51.428571 0 1338.874847 Tm 6.338889 0 Td 62.654321 Tz (was ) Tj 1.341667 0 Td 55.740741 Tz (based ) Tj 1.886111 0 Td 59.143519 Tz (upon ) Tj 1.633333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 46.254209 Tz (realization ) Tj 3.286111 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 46.296296 Tz (certain ) Tj 2.158333 0 Td 45.694444 Tz (structural ) Tj 2.955556 0 Td 54.62963 Tz (require ) Tj 51.428571 0 0 51.428571 0 1296.979899 Tm 6.358333 0 Td 57.685185 Tz (ments ) Tj 1.983333 0 Td 48.611111 Tz (for ) Tj 1.088889 0 Td 54.012346 Tz (proper ) Tj 2.197222 0 Td 44.722222 Tz (reactivity ) Tj 2.955556 0 Td 52.662037 Tz (with ) Tj 1.516667 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 77.777778 Tz (ATX ) Tj 1.652778 0 Td 64.00463 Tz (compound ) Tj 3.344444 0 Td 37.962963 Tz (itself. ) Tj 51.428571 0 0 51.428571 0 1251.947368 Tm 6.377778 0 Td 52.572016 Tz (Extensive ) Tj 3.188889 0 Td 51.851852 Tz (review ) Tj 2.236111 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 49.826389 Tz (possible ) Tj 2.722222 0 Td 61.574074 Tz (compounds ) Tj 3.694444 0 Td 61.574074 Tz (was ) Tj 1.438889 0 Td 54.444444 Tz (undertaken ) Tj 51.428571 0 0 51.428571 0 1213.346784 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.663889 0 Td 57.118056 Tz (computer ) Tj 3.091667 0 Td 57.118056 Tz (modeling ) Tj 3.072222 0 Td 58.333333 Tz (of ) Tj 0.991667 0 Td 47.170782 Tz (similarly ) Tj 2.916667 0 Td 48.611111 Tz (structured ) Tj 3.247222 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1167.865337 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.313889 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 51.203704 Tz (types ) Tj 1.769444 0 Td 53.796296 Tz (noted ) Tj 1.808333 0 Td 57.685185 Tz (above ) Tj 1.944444 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 50.411523 Tz (exhibited ) Tj 2.897222 0 Td 77.777778 Tz (ATX ) Tj 1.633333 0 Td 53.472222 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 1128.136253 Tm 6.338889 0 Td 44.074074 Tz (tion, ) Tj 1.477778 0 Td 50.771605 Tz (but ) Tj 1.069444 0 Td 50.771605 Tz (did ) Tj 1.05 0 Td 50.771605 Tz (not ) Tj 1.05 0 Td 51.851852 Tz (pass ) Tj 1.4 0 Td 46.180556 Tz (oral ) Tj 1.263889 0 Td 46.234568 Tz (bioavailability ) Tj 4.316667 0 Td 42.12963 Tz (test ) Tj 1.108333 0 Td 47.638889 Tz (protocols. ) Tj 3.072222 0 Td 37.268519 Tz (It ) Tj 0.583333 0 Td 60.493827 Tz (was ) Tj 51.428571 0 0 51.428571 0 1083.740214 Tm 6.358333 0 Td 52.146465 Tz (determined, ) Tj 3.597222 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 47.170782 Tz (instance, ) Tj 2.683333 0 Td 46.180556 Tz (that ) Tj 1.263889 0 Td 46.296296 Tz (certain ) Tj 2.1 0 Td 50.555556 Tz (types ) Tj 1.672222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 58.333333 Tz (backbone ) Tj 2.916667 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1044.352657 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.275 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 44.722222 Tz (effective, ) Tj 2.838889 0 Td 47.314815 Tz (generally, ) Tj 2.975 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 50.231481 Tz (theory ) Tj 1.983333 0 Td 48.611111 Tz (for ) Tj 0.952778 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 56.712963 Tz (inhi ) Tj 51.428571 0 0 51.428571 0 1002.78392 Tm 6.338889 0 Td 44.444444 Tz (bition. ) Tj 2.197222 0 Td 57.118056 Tz (However, ) Tj 3.013889 0 Td 49.691358 Tz (closer ) Tj 2.022222 0 Td 48.206019 Tz (scrutiny ) Tj 2.625 0 Td 61.574074 Tz (was ) Tj 1.419444 0 Td 56.17284 Tz (needed ) Tj 2.294444 0 Td 46.990741 Tz (to ) Tj 0.855556 0 Td 46.548822 Tz (effectively ) Tj 51.428571 0 0 51.428571 0 963.159269 Tm 6.358333 0 Td 53.703704 Tz (analyze ) Tj 2.411111 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 48.070988 Tz (actual ) Tj 1.925 0 Td 47.314815 Tz (capability ) Tj 3.052778 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 55.092593 Tz (each ) Tj 1.497222 0 Td 53.472222 Tz (type ) Tj 1.477778 0 Td 55.092593 Tz (of ) Tj 0.758333 0 Td 59.773663 Tz (compound. ) Tj 51.428571 0 0 51.428571 0 918.182519 Tm 7.116667 0 Td 46.990741 Tz (In ) Tj 0.719444 0 Td 50.231481 Tz (essence, ) Tj 2.605556 0 Td 34.027778 Tz (it ) Tj 0.563889 0 Td 61.574074 Tz (was ) Tj 1.283333 0 Td 55.092593 Tz (determined ) Tj 3.441667 0 Td 53.240741 Tz (through ) Tj 2.411111 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 58.981481 Tz (model ) Tj 1.944444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 877.728443 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.780556 0 Td 56.018519 Tz (domain, ) Tj 2.722222 0 Td 48.611111 Tz (residues ) Tj 2.761111 0 Td 55.555556 Tz (162-539 ) Tj 2.683333 0 Td 57.523148 Tz (from ) Tj 1.730556 0 Td 47.530864 Tz (the ) Tj 1.186111 0 Td 56.30787 Tz (sequence ) Tj 2.994444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 836.226572 Tm 6.338889 0 Td 66.759259 Tz (human ) Tj 2.1 0 Td 65.625 Tz (ATX, ) Tj 1.711111 0 Td 54.73251 Tz (developed ) Tj 3.072222 0 Td 58.333333 Tz (by ) Tj 0.816667 0 Td 61.574074 Tz (homology ) Tj 3.091667 0 Td 43.75 Tz (to ) Tj 0.661111 0 Td 64.814815 Tz (Xac ) Tj 1.302778 0 Td 58.333333 Tz (NPP, ) Tj 1.555556 0 Td 45.37037 Tz (that ) Tj 1.186111 0 Td 48.148148 Tz (certain ) Tj 51.428571 0 0 51.428571 0 794.866104 Tm 6.338889 0 Td 49.907407 Tz (basic ) Tj 1.672222 0 Td 49.537037 Tz (configurations ) Tj 4.316667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 75.617284 Tz (ATX ) Tj 1.555556 0 Td 46.018519 Tz (inhibitors ) Tj 2.955556 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 58.333333 Tz (most ) Tj 1.575 0 Td 44.830247 Tz (likely ) Tj 1.808333 0 Td 68.055556 Tz (nec ) Tj 51.428571 0 0 51.428571 0 751.014085 Tm 6.358333 0 Td 45.833333 Tz (essary. ) Tj 2.138889 0 Td 54.552469 Tz (Within ) Tj 2.177778 0 Td 42.12963 Tz (this ) Tj 1.244444 0 Td 54.012346 Tz (model, ) Tj 2.138889 0 Td 35.648148 Tz (it ) Tj 0.602778 0 Td 61.574074 Tz (was ) Tj 1.322222 0 Td 53.148148 Tz (noted ) Tj 1.788889 0 Td 45.37037 Tz (that ) Tj 1.263889 0 Td 38.888889 Tz (all ) Tj 0.875 0 Td 51.851852 Tz (but ) Tj 1.127778 0 Td 58.333333 Tz (4 ) Tj 0.563889 0 Td 59.953704 Tz (\(1%\) ) Tj 1.613889 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 714.368047 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 60.493827 Tz (317 ) Tj 1.263889 0 Td 51.262626 Tz (non-proline ) Tj 3.519444 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 52.441077 Tz (non-glycine ) Tj 3.597222 0 Td 49.016204 Tz (residues ) Tj 2.527778 0 Td 57.253086 Tz (occupy ) Tj 2.216667 0 Td 50.462963 Tz (regions ) Tj 51.428571 0 0 51.428571 0 670.843787 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.758333 0 Td 60.493827 Tz (Ramachandran ) Tj 4.530556 0 Td 53.796296 Tz (space ) Tj 1.75 0 Td 50.968013 Tz (categorized ) Tj 3.5 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 51.851852 Tz (core ) Tj 1.419444 0 Td 54.012346 Tz (secondary ) Tj 3.091667 0 Td 54.444444 Tz (struc ) Tj 51.428571 0 0 51.428571 0 627.121887 Tm 6.338889 0 Td 47.314815 Tz (tures ) Tj 1.808333 0 Td 54.282407 Tz (\(232 ) Tj 1.691667 0 Td 46.8107 Tz (residues, ) Tj 2.897222 0 Td 57.685185 Tz (73%\), ) Tj 2.080556 0 Td 54.62963 Tz (allowed ) Tj 2.683333 0 Td 49.537037 Tz (regions ) Tj 2.430556 0 Td 54.012346 Tz (\(75 ) Tj 1.361111 0 Td 46.450617 Tz (residues, ) Tj 51.428571 0 0 51.428571 0 586.663391 Tm 6.358333 0 Td 66.435185 Tz (24%\) ) Tj 1.769444 0 Td 53.472222 Tz (or ) Tj 0.816667 0 Td 52.824074 Tz (generously ) Tj 3.363889 0 Td 55.092593 Tz (allowed ) Tj 2.527778 0 Td 50 Tz (regions ) Tj 2.313889 0 Td 48.611111 Tz (\(6 ) Tj 0.816667 0 Td 46.8107 Tz (residues, ) Tj 2.741667 0 Td 56.712963 Tz (2%\). ) Tj 1.575 0 Td 51.203704 Tz (\(This ) Tj 51.428571 0 0 51.428571 0 544.220452 Tm 6.358333 0 Td 60.277778 Tz (model ) Tj 2.138889 0 Td 52.662037 Tz (was, ) Tj 1.575 0 Td 48.070988 Tz (again, ) Tj 2.061111 0 Td 55.092593 Tz (used ) Tj 1.613889 0 Td 45.37037 Tz (in ) Tj 0.855556 0 Td 55.555556 Tz (docking ) Tj 2.625 0 Td 47.685185 Tz (studies ) Tj 2.313889 0 Td 52.662037 Tz (with ) Tj 1.575 0 Td 59.41358 Tz (two ) Tj 1.4 0 Td 72.376543 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 504.817509 Tm 6.377778 0 Td 46.990741 Tz (species, ) Tj 2.508333 0 Td 51.851852 Tz (12:0 ) Tj 1.380556 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 47.314815 Tz (14:0, ) Tj 1.594444 0 Td 62.222222 Tz (shown ) Tj 2.041667 0 Td 50.87963 Tz (previously ) Tj 3.266667 0 Td 43.75 Tz (to ) Tj 0.7 0 Td 59.953704 Tz (be ) Tj 0.875 0 Td 52.777778 Tz (optimal ) Tj 2.372222 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 461.291215 Tm 6.377778 0 Td 45.640432 Tz (substrates.\) ) Tj 3.461111 0 Td 51.851852 Tz (Unrestrained ) Tj 3.927778 0 Td 56.481481 Tz (docking ) Tj 2.527778 0 Td 47.685185 Tz (studies ) Tj 2.197222 0 Td 45.910494 Tz (failed ) Tj 1.847222 0 Td 43.75 Tz (to ) Tj 0.719444 0 Td 46.990741 Tz (identify ) Tj 2.45 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 421.524941 Tm 6.358333 0 Td 55.902778 Tz (pose ) Tj 1.477778 0 Td 51.388889 Tz (placing ) Tj 2.294444 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 56.271044 Tz (phosphorous ) Tj 3.869444 0 Td 59.953704 Tz (atom ) Tj 1.633333 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 46.990741 Tz (either ) Tj 1.827778 0 Td 47.530864 Tz (Substrate ) Tj 2.722222 0 Td 52.391975 Tz (within ) Tj 51.428571 0 0 51.428571 0 378.336196 Tm 6.358333 0 Td 51.851852 Tz (a ) Tj 0.563889 0 Td 51.527778 Tz (reasonable ) Tj 3.305556 0 Td 50.231481 Tz (distance ) Tj 2.566667 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 57.685185 Tz (T210, ) Tj 1.963889 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 45.730453 Tz (catalytic ) Tj 2.741667 0 Td 49.537037 Tz (residue ) Tj 2.294444 0 Td 59.953704 Tz (respon ) Tj 51.428571 0 0 51.428571 0 339.425743 Tm 6.377778 0 Td 44.722222 Tz (sible ) Tj 1.555556 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 43.75 Tz (initiating ) Tj 2.8 0 Td 50.231481 Tz (hydrolysis ) Tj 3.227778 0 Td 59.953704 Tz (by ) Tj 0.933333 0 Td 55.555556 Tz (forming ) Tj 2.527778 0 Td 51.851852 Tz (a ) Tj 0.505556 0 Td 51.041667 Tz (covalent ) Tj 2.625 0 Td 61.574074 Tz (bond ) Tj 1.652778 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 294.94155 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 56.271044 Tz (phosphorous ) Tj 3.986111 0 Td 53.796296 Tz (atom. ) Tj 1.886111 0 Td 52.662037 Tz (This ) Tj 1.594444 0 Td 43.75 Tz (result ) Tj 1.866667 0 Td 60.493827 Tz (was ) Tj 1.341667 0 Td 49.259259 Tz (consistent ) Tj 3.188889 0 Td 53.472222 Tz (with ) Tj 1.575 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 253.511515 Tm 6.358333 0 Td 48.611111 Tz (report ) Tj 1.944444 0 Td 46.180556 Tz (that ) Tj 1.302778 0 Td 47.890947 Tz (Substrate ) Tj 2.8 0 Td 49.789562 Tz (recognition ) Tj 3.5 0 Td 53.472222 Tz (elements ) Tj 2.8 0 Td 48.070988 Tz (reside ) Tj 1.944444 0 Td 50.462963 Tz (outside ) Tj 2.294444 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 211.232274 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.625 0 Td 55.555556 Tz (domain. ) Tj 2.527778 0 Td 54.444444 Tz (Poses ) Tj 1.769444 0 Td 48.935185 Tz (consistent ) Tj 3.111111 0 Td 51.851852 Tz (with ) Tj 1.438889 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 45.37037 Tz (role ) Tj 1.244444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 73.45679 Tz (LPC ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 61.574074 Tz (an ) Tj 40 0 0 40 0 176 Tm 8.175 0 Td 101.388889 Tz (ATX ) Tj 2.2 0 Td 61.574074 Tz (substrate ) Tj 3.7 0 Td 76.041667 Tz (were ) Tj 2.2 0 Td 58.75 Tz (identified ) Tj 3.9 0 Td 83.333333 Tz (when ) Tj 2.375 0 Td 72.916667 Tz (an ) Tj 1.275 0 Td 64.880952 Tz (anionic ) Tj 3.1 0 Td 77.083333 Tz (atom ) Tj 2.25 0 Td 80.555556 Tz (was ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.9 0 Td 69.369369 Tz (6 ) Tj 58.571429 0 0 58.571429 0 2915.526708 Tm 22.195122 0 Td 45.172764 Tz (required ) Tj 2.304878 0 Td 41.260163 Tz (to ) Tj 0.665854 0 Td 48.373984 Tz (occur ) Tj 1.570732 0 Td 45.528455 Tz (within ) Tj 1.77561 0 Td 51.219512 Tz (a ) Tj 0.478049 0 Td 44.579946 Tz (3.6 ) Tj 0.973171 0 Td 76.829268 Tz (A ) Tj 0.597561 0 Td 46.95122 Tz (sphere ) Tj 1.809756 0 Td 45.884146 Tz (centered ) Tj 2.339024 0 Td 45.528455 Tz (4.6 ) Tj 0.973171 0 Td 76.829268 Tz (A ) Tj 0.631707 0 Td 51.930894 Tz (from ) Tj 58.571429 0 0 58.571429 0 2874.05036 Tm 22.195122 0 Td 48.373984 Tz (both ) Tj 1.280488 0 Td 48.057814 Tz (metalions ) Tj 2.697561 0 Td 52.168022 Tz (and ) Tj 1.007317 0 Td 44.579946 Tz (2.8 ) Tj 0.956098 0 Td 71.138211 Tz (A ) Tj 0.529268 0 Td 52.642276 Tz (from ) Tj 1.382927 0 Td 42.682927 Tz (the ) Tj 0.904878 0 Td 54.065041 Tz (oxygenatom ) Tj 3.380488 0 Td 45.528455 Tz (of ) Tj 0.631707 0 Td 48.943089 Tz (T210. ) Tj 1.570732 0 Td 56.910569 Tz (The ) Tj 58.571429 0 0 58.571429 0 2833.75662 Tm 22.195122 0 Td 49.92609 Tz (phosphorous ) Tj 3.482927 0 Td 52.642276 Tz (atom ) Tj 1.485366 0 Td 31.300813 Tz (still ) Tj 1.143902 0 Td 43.631436 Tz (preferred ) Tj 2.560976 0 Td 48.373984 Tz (a ) Tj 0.495122 0 Td 42.682927 Tz (location ) Tj 2.253659 0 Td 47.425474 Tz (6-7 ) Tj 1.058537 0 Td 76.829268 Tz (A ) Tj 0.64878 0 Td 51.219512 Tz (from ) Tj 1.434146 0 Td 44.579946 Tz (the ) Tj 51.428571 0 0 51.428571 0 2792.886076 Tm 25.297222 0 Td 62.546296 Tz (oxygenatom ) Tj 3.947222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 57.037037 Tz (T210. ) Tj 51.428571 0 0 51.428571 0 2749.986129 Tm 26.036111 0 Td 48.611111 Tz (In ) Tj 0.719444 0 Td 49.074074 Tz (greater ) Tj 2.197222 0 Td 42.12963 Tz (detail, ) Tj 1.886111 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 59.62963 Tz (model ) Tj 1.925 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 66.111111 Tz (human ) Tj 2.080556 0 Td 78.858025 Tz (ATX ) Tj 1.555556 0 Td 60.493827 Tz (was ) Tj 1.263889 0 Td 55.092593 Tz (developed ) Tj 3.111111 0 Td 59.953704 Tz (by ) Tj 51.428571 0 0 51.428571 0 2710.036662 Tm 25.277778 0 Td 61.574074 Tz (homology ) Tj 3.383333 0 Td 46.990741 Tz (to ) Tj 0.991667 0 Td 50.771605 Tz (the ) Tj 1.322222 0 Td 65.895062 Tz (Xac ) Tj 1.633333 0 Td 50.555556 Tz (nucleotide ) Tj 3.422222 0 Td 56.064815 Tz (pyrophosphatase/phos ) Tj 51.428571 0 0 51.428571 0 2667.762999 Tm 25.297222 0 Td 50.854701 Tz (phodiesterase ) Tj 4.122222 0 Td 59.62963 Tz (\(NPP\) ) Tj 1.944444 0 Td 45.37037 Tz (crystal ) Tj 2.061111 0 Td 47.530864 Tz (structure ) Tj 2.722222 0 Td 46.990741 Tz (\(entry ) Tj 1.866667 0 Td 75.617284 Tz (2CSU31 ) Tj 3.169444 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2623.331725 Tm 25.316667 0 Td 49.074074 Tz (Protein ) Tj 2.275 0 Td 55.092593 Tz (Data ) Tj 1.555556 0 Td 52.391975 Tz (Bank\). ) Tj 2.061111 0 Td 62.654321 Tz (The ) Tj 1.283333 0 Td 55.902778 Tz (sequence ) Tj 2.838889 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 65.462963 Tz (human ) Tj 2.1 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 62.384259 Tz (\(GenBank ) Tj 51.428571 0 0 51.428571 0 2584.254408 Tm 25.297222 0 Td 49.259259 Tz (entry ) Tj 1.730556 0 Td 62.037037 Tz (Q13822\) ) Tj 2.819444 0 Td 62.654321 Tz (was ) Tj 1.380556 0 Td 50.925926 Tz (aligned ) Tj 2.372222 0 Td 54.282407 Tz (with ) Tj 1.555556 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 55.497685 Tz (sequence ) Tj 2.877778 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 65.895062 Tz (Xac ) Tj 1.419444 0 Td 74.537037 Tz (NPP ) Tj 51.428571 0 0 51.428571 0 2539.795152 Tm 25.277778 0 Td 53.148148 Tz (using ) Tj 1.730556 0 Td 89.660494 Tz (MOE ) Tj 1.730556 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 60.277778 Tz (amino ) Tj 1.925 0 Td 50.555556 Tz (acids ) Tj 1.711111 0 Td 52.5 Tz (1-161 ) Tj 1.75 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 56.481481 Tz (540-863 ) Tj 2.547222 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 75.617284 Tz (ATX ) Tj 1.516667 0 Td 59.143519 Tz (were ) Tj 51.428571 0 0 51.428571 0 2499.188769 Tm 25.297222 0 Td 50 Tz (deleted ) Tj 2.216667 0 Td 50.231481 Tz (as ) Tj 0.719444 0 Td 51.041667 Tz (they ) Tj 1.380556 0 Td 50.771605 Tz (did ) Tj 1.05 0 Td 50.771605 Tz (not ) Tj 1.030556 0 Td 53.796296 Tz (correspond ) Tj 3.305556 0 Td 48.611111 Tz (to ) Tj 0.680556 0 Td 61.574074 Tz (amino ) Tj 1.944444 0 Td 49.907407 Tz (acids ) Tj 1.652778 0 Td 51.851852 Tz (contained ) Tj 2.936111 0 Td 46.990741 Tz (in ) Tj 51.428571 0 0 51.428571 0 2457.730496 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 73.45679 Tz (XacNPP ) Tj 2.722222 0 Td 45.046296 Tz (structure. ) Tj 2.838889 0 Td 62.654321 Tz (The ) Tj 1.225 0 Td 76.697531 Tz (ATX ) Tj 1.516667 0 Td 59.62963 Tz (model ) Tj 1.905556 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 51.041667 Tz (then ) Tj 1.361111 0 Td 52.211934 Tz (generated ) Tj 2.916667 0 Td 61.574074 Tz (by ) Tj 51.428571 0 0 51.428571 0 2415.531052 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 61.168981 Tz (homology ) Tj 3.227778 0 Td 59.62963 Tz (model ) Tj 2.041667 0 Td 50.231481 Tz (function ) Tj 2.683333 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 75.347222 Tz (MOE, ) Tj 2.041667 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 47.395833 Tz (divalent ) Tj 2.586111 0 Td 52.5 Tz (metal ) Tj 51.428571 0 0 51.428571 0 2375.100122 Tm 25.297222 0 Td 48.611111 Tz (cations ) Tj 2.275 0 Td 59.143519 Tz (were ) Tj 1.613889 0 Td 48.316498 Tz (transferred ) Tj 3.383333 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 53.596866 Tz (corresponding ) Tj 4.394444 0 Td 48.251029 Tz (locations ) Tj 2.858333 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2331.981413 Tm 25.297222 0 Td 58.333333 Tz (from ) Tj 1.633333 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 65.895062 Tz (Xac ) Tj 1.380556 0 Td 75.617284 Tz (NPP ) Tj 1.536111 0 Td 45.833333 Tz (crystal ) Tj 2.119444 0 Td 45.046296 Tz (structure. ) Tj 2.955556 0 Td 47.962963 Tz (Ionization ) Tj 3.130556 0 Td 44.290123 Tz (states ) Tj 1.788889 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 59.41358 Tz (his ) Tj 51.428571 0 0 51.428571 0 2291.25 Tm 25.277778 0 Td 46.990741 Tz (tidine ) Tj 1.925 0 Td 49.016204 Tz (residues ) Tj 2.625 0 Td 51.851852 Tz (near ) Tj 1.438889 0 Td 48.206019 Tz (divalent ) Tj 2.547222 0 Td 51.851852 Tz (metal ) Tj 1.827778 0 Td 48.611111 Tz (cations ) Tj 2.294444 0 Td 57.523148 Tz (were ) Tj 1.613889 0 Td 50.636574 Tz (adjusted ) Tj 2.644444 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 2251.967328 Tm 25.297222 0 Td 51.851852 Tz (Zero ) Tj 1.380556 0 Td 49.537037 Tz (charge, ) Tj 2.197222 0 Td 54.282407 Tz (with ) Tj 1.380556 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 52.662037 Tz (deprotonated ) Tj 3.908333 0 Td 53.292181 Tz (imidazole ) Tj 3.013889 0 Td 49.826389 Tz (nitrogen ) Tj 2.508333 0 Td 49.074074 Tz (nearest ) Tj 51.428571 0 0 51.428571 0 2207.263158 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 46.759259 Tz (cation. ) Tj 2.158333 0 Td 64.814815 Tz (The ) Tj 1.380556 0 Td 47.962963 Tz (ionization ) Tj 3.091667 0 Td 44.722222 Tz (state ) Tj 1.536111 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 64.814815 Tz (T210 ) Tj 1.75 0 Td 62.654321 Tz (was ) Tj 1.302778 0 Td 51.041667 Tz (adjusted ) Tj 2.663889 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 49.691358 Tz (-1, ) Tj 51.428571 0 0 51.428571 0 2166.473952 Tm 25.297222 0 Td 48.611111 Tz (consistent ) Tj 3.091667 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 76.157407 Tz (pH ) Tj 1.088889 0 Td 45.37037 Tz (profile ) Tj 2.080556 0 Td 54.552469 Tz (demonstrated ) Tj 4.122222 0 Td 47.530864 Tz (for ) Tj 0.991667 0 Td 65.895062 Tz (Xac ) Tj 1.380556 0 Td 58.333333 Tz (NPP. ) Tj 51.428571 0 0 51.428571 0 2126.185567 Tm 26.016667 0 Td 60.493827 Tz (Complexes ) Tj 3.5 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 77.777778 Tz (ATX ) Tj 1.652778 0 Td 52.662037 Tz (with ) Tj 1.536111 0 Td 51.851852 Tz (small ) Tj 1.847222 0 Td 53.652263 Tz (molecules ) Tj 3.169444 0 Td 50.771605 Tz (including ) Tj 2.975 0 Td 69.135802 Tz (sub ) Tj 51.428571 0 0 51.428571 0 2083.433414 Tm 25.316667 0 Td 42.12963 Tz (strates, ) Tj 2.255556 0 Td 44.781145 Tz (inhibitors, ) Tj 3.188889 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 51.851852 Tz (candidate ) Tj 3.033333 0 Td 44.486532 Tz (inhibitors, ) Tj 3.208333 0 Td 58.333333 Tz (were ) Tj 1.613889 0 Td 53.292181 Tz (generated ) Tj 51.428571 0 0 51.428571 0 2042.381071 Tm 25.277778 0 Td 61.574074 Tz (by ) Tj 0.972222 0 Td 55.555556 Tz (docking ) Tj 2.547222 0 Td 52.5 Tz (using ) Tj 1.788889 0 Td 72.106481 Tz (MOE. ) Tj 2.041667 0 Td 57.523148 Tz (Each ) Tj 1.594444 0 Td 51.851852 Tz (small ) Tj 1.808333 0 Td 55.497685 Tz (molecule ) Tj 2.877778 0 Td 46.8107 Tz (structure ) Tj 2.741667 0 Td 61.574074 Tz (was ) Tj 51.428571 0 0 51.428571 0 2000.829733 Tm 25.297222 0 Td 50.968013 Tz (constructed ) Tj 3.597222 0 Td 45.37037 Tz (in ) Tj 0.797222 0 Td 51.851852 Tz (the ) Tj 1.166667 0 Td 47.962963 Tz (ionization ) Tj 3.130556 0 Td 44.722222 Tz (state ) Tj 1.555556 0 Td 54.282407 Tz (expected ) Tj 2.819444 0 Td 45.37037 Tz (at ) Tj 0.777778 0 Td 74.537037 Tz (pH ) Tj 1.127778 0 Td 43.75 Tz (7. ) Tj 0.816667 0 Td 69.675926 Tz (Func ) Tj 51.428571 0 0 51.428571 0 1960.113831 Tm 25.277778 0 Td 46.450617 Tz (tional ) Tj 1.827778 0 Td 55.632716 Tz (groups ) Tj 2.177778 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 68.055556 Tz (pKa ) Tj 1.438889 0 Td 49.691358 Tz (values ) Tj 1.983333 0 Td 52.662037 Tz (near ) Tj 1.419444 0 Td 49.691358 Tz (seven, ) Tj 1.963889 0 Td 55.092593 Tz (such ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 54.73251 Tz (phosphate ) Tj 51.428571 0 0 51.428571 0 1918.209756 Tm 25.297222 0 Td 52.73569 Tz (monoesters, ) Tj 3.733333 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 52.662037 Tz (deprotonated ) Tj 4.005556 0 Td 58.333333 Tz (due ) Tj 1.244444 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 54.282407 Tz (expected ) Tj 2.819444 0 Td 50.925926 Tz (anionic ) Tj 51.428571 0 0 51.428571 0 1875.658537 Tm 25.316667 0 Td 45.121083 Tz (stabilization ) Tj 3.713889 0 Td 53.472222 Tz (provided ) Tj 2.722222 0 Td 61.574074 Tz (by ) Tj 0.933333 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 48.611111 Tz (active ) Tj 1.925 0 Td 41.319444 Tz (site ) Tj 1.186111 0 Td 51.851852 Tz (metal ) Tj 1.769444 0 Td 45.37037 Tz (ions. ) Tj 1.594444 0 Td 53.877315 Tz (Residues ) Tj 47.142857 0 0 47.142857 0 1840 Tm 27.575758 0 Td 59.217172 Tz (with ) Tj 1.69697 0 Td 63.636364 Tz (atoms ) Tj 2.142424 0 Td 57.154882 Tz (within ) Tj 2.333333 0 Td 53.030303 Tz (6.5 ) Tj 1.230303 0 Td 95.454545 Tz (A ) Tj 0.848485 0 Td 65.40404 Tz (of ) Tj 0.954545 0 Td 53.030303 Tz (the ) Tj 1.187879 0 Td 52.441077 Tz (active ) Tj 2.142424 0 Td 46.843434 Tz (site ) Tj 1.4 0 Td 57.979798 Tz (metal ) Tj 2.036364 0 Td 53.914141 Tz (ions ) Tj 1.569697 0 Td 64.520202 Tz (were ) Tj 51.428571 0 0 51.428571 0 1793.508642 Tm 25.297222 0 Td 51.388889 Tz (defined ) Tj 2.333333 0 Td 51.851852 Tz (as ) Tj 0.855556 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 56.17284 Tz (placement ) Tj 3.247222 0 Td 38.888889 Tz (site. ) Tj 1.4 0 Td 55.740741 Tz (Small ) Tj 1.925 0 Td 54.012346 Tz (molecules ) Tj 3.15 0 Td 58.333333 Tz (were ) Tj 1.613889 0 Td 52.932099 Tz (placed ) Tj 51.428571 0 0 51.428571 0 1752.989583 Tm 25.297222 0 Td 46.180556 Tz (into ) Tj 1.458333 0 Td 77.777778 Tz (ATX ) Tj 1.769444 0 Td 52.5 Tz (using ) Tj 1.925 0 Td 49.691358 Tz (the ) Tj 1.244444 0 Td 59.548611 Tz (alphaPMI ) Tj 3.208333 0 Td 55.812757 Tz (placement ) Tj 3.402778 0 Td 55.092593 Tz (method, ) Tj 2.702778 0 Td 58.981481 Tz (which ) Tj 51.428571 0 0 51.428571 0 1709.321909 Tm 25.297222 0 Td 56.481481 Tz (matches ) Tj 2.566667 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 51.203704 Tz (Small ) Tj 1.769444 0 Td 55.497685 Tz (molecule ) Tj 2.838889 0 Td 48.611111 Tz (principle ) Tj 2.838889 0 Td 62.962963 Tz (moments ) Tj 2.858333 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 44.444444 Tz (inertia ) Tj 2.061111 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 1669.921951 Tm 25.297222 0 Td 52.5 Tz (alpha ) Tj 1.788889 0 Td 51.388889 Tz (spheres ) Tj 2.372222 0 Td 47.138047 Tz (distributed ) Tj 3.325 0 Td 45.37037 Tz (in ) Tj 0.777778 0 Td 48.148148 Tz (closely ) Tj 2.255556 0 Td 57.253086 Tz (packed ) Tj 2.255556 0 Td 48.251029 Tz (locations ) Tj 2.838889 0 Td 51.851852 Tz (within ) Tj 52.857143 0 0 52.857143 0 1625.749701 Tm 24.594595 0 Td 49.399399 Tz (the ) Tj 1.021622 0 Td 54.504505 Tz (docking ) Tj 2.440541 0 Td 37.207207 Tz (site. ) Tj 1.267568 0 Td 54.864865 Tz (Small ) Tj 1.816216 0 Td 53.997748 Tz (molecule ) Tj 2.724324 0 Td 51.711712 Tz (poses ) Tj 1.702703 0 Td 57.545045 Tz (were ) Tj 1.532432 0 Td 50.975976 Tz (scored ) Tj 1.92973 0 Td 52.972973 Tz (using ) Tj 1.683784 0 Td 50.45045 Tz (the ) Tj 51.428571 0 0 51.428571 0 1586.294331 Tm 25.297222 0 Td 42.939815 Tz (affinity ) Tj 2.138889 0 Td 81.018519 Tz (DG ) Tj 1.205556 0 Td 47.530864 Tz (function, ) Tj 2.780556 0 Td 58.981481 Tz (which ) Tj 1.983333 0 Td 54.282407 Tz (approximates ) Tj 4.141667 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 49.691358 Tz (enthalpic ) Tj 2.897222 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 1543.074663 Tm 25.277778 0 Td 46.090535 Tz (tribution ) Tj 2.722222 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 53.240741 Tz (binding ) Tj 2.430556 0 Td 47.800926 Tz (free ) Tj 1.322222 0 Td 49.537037 Tz (energy. ) Tj 2.313889 0 Td 53.472222 Tz (This ) Tj 1.516667 0 Td 54.79798 Tz (combination ) Tj 3.830556 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 59.62963 Tz (place ) Tj 51.428571 0 0 51.428571 0 1501.727273 Tm 25.297222 0 Td 60.763889 Tz (ment ) Tj 1.594444 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 50.925926 Tz (scoring ) Tj 2.313889 0 Td 57.87037 Tz (methods ) Tj 2.586111 0 Td 60.493827 Tz (was ) Tj 1.263889 0 Td 48.611111 Tz (selected ) Tj 2.469444 0 Td 55.092593 Tz (based ) Tj 1.808333 0 Td 58.333333 Tz (on ) Tj 0.855556 0 Td 56.712963 Tz (comparison ) Tj 51.428571 0 0 51.428571 0 1461.180268 Tm 25.297222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 45.37037 Tz (results ) Tj 2.061111 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 58.333333 Tz (two ) Tj 1.263889 0 Td 42.939815 Tz (test ) Tj 1.205556 0 Td 51.041667 Tz (systems. ) Tj 2.644444 0 Td 62.654321 Tz (The ) Tj 1.302778 0 Td 59.548611 Tz (alphaDMI ) Tj 3.033333 0 Td 56.17284 Tz (placement ) Tj 3.169444 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1419.625147 Tm 25.297222 0 Td 54.282407 Tz (affinityDGenergy ) Tj 5.347222 0 Td 50.231481 Tz (function ) Tj 2.547222 0 Td 59.143519 Tz (were ) Tj 1.555556 0 Td 56.388889 Tz (found ) Tj 1.808333 0 Td 46.990741 Tz (to ) Tj 0.719444 0 Td 53.652263 Tz (reproduce ) Tj 3.013889 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 60.763889 Tz (crys ) Tj 51.428571 0 0 51.428571 0 1378.706444 Tm 25.277778 0 Td 48.341049 Tz (tallographic ) Tj 3.616667 0 Td 49.016204 Tz (position ) Tj 2.488889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 48.112536 Tz (rosiglitazone ) Tj 3.888889 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 67.407407 Tz (PPARY ) Tj 2.158333 0 Td 50.231481 Tz (as ) Tj 0.758333 0 Td 51.851852 Tz (well ) Tj 1.380556 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 56.17284 Tz (our ) Tj 51.428571 0 0 51.428571 0 1337.817308 Tm 25.297222 0 Td 51.446759 Tz (previous ) Tj 2.722222 0 Td 57.79321 Tz (docked ) Tj 2.275 0 Td 48.611111 Tz (position ) Tj 2.547222 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 52.73569 Tz (sphingosine ) Tj 3.752778 0 Td 52.73569 Tz (1-phosphate ) Tj 3.713889 0 Td 54.444444 Tz (\(S1P\) ) Tj 52.857143 0 0 52.857143 0 1292.65285 Tm 24.594595 0 Td 50.975976 Tz (within ) Tj 2.1 0 Td 48.348348 Tz (the ) Tj 1.135135 0 Td 47.997998 Tz (validated ) Tj 2.856757 0 Td 58.648649 Tz (model ) Tj 2.043243 0 Td 55.18018 Tz (of ) Tj 0.889189 0 Td 47.297297 Tz (the ) Tj 1.116216 0 Td 66.216216 Tz (S1P ) Tj 1.721622 0 Td 44.844845 Tz (receptor. ) Tj 2.724324 0 Td 57.657658 Tz (Docking ) Tj 51.428571 0 0 51.428571 0 1250.390453 Tm 25.316667 0 Td 50.378788 Tz (simulations ) Tj 3.538889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 51.851852 Tz (Small ) Tj 1.808333 0 Td 54.372428 Tz (molecules ) Tj 3.130556 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 54.282407 Tz (long ) Tj 1.477778 0 Td 48.611111 Tz (alkyl ) Tj 1.652778 0 Td 51.311728 Tz (chains ) Tj 2.041667 0 Td 63.194444 Tz (addi ) Tj 51.428571 0 0 51.428571 0 1211.844282 Tm 25.277778 0 Td 46.585648 Tz (tionally ) Tj 2.430556 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 56.17284 Tz (performed ) Tj 3.227778 0 Td 50.231481 Tz (multiple ) Tj 2.605556 0 Td 51.851852 Tz (times ) Tj 1.75 0 Td 58.333333 Tz (due ) Tj 1.225 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 47.314815 Tz (stochastic ) Tj 51.428571 0 0 51.428571 0 1169.080214 Tm 25.297222 0 Td 50.771605 Tz (nature ) Tj 2.333333 0 Td 58.333333 Tz (of ) Tj 1.108333 0 Td 50.771605 Tz (the ) Tj 1.419444 0 Td 52.546296 Tz (conformational ) Tj 4.958333 0 Td 55.497685 Tz (sampling ) Tj 3.15 0 Td 54.372428 Tz (procedure ) Tj 3.422222 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1125.64277 Tm 25.297222 0 Td 51.851852 Tz (included ) Tj 2.722222 0 Td 55.092593 Tz (an ) Tj 0.894444 0 Td 51.131687 Tz (increased ) Tj 3.013889 0 Td 61.033951 Tz (number ) Tj 2.411111 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 55.555556 Tz (samples ) Tj 2.566667 0 Td 52.932099 Tz (per ) Tj 1.147222 0 Td 54.552469 Tz (conformation ) Tj 51.428571 0 0 51.428571 0 1085.174142 Tm 25.316667 0 Td 49.421296 Tz (\(50\) ) Tj 1.497222 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 58.333333 Tz (an ) Tj 1.030556 0 Td 50.771605 Tz (increased ) Tj 3.052778 0 Td 62.114198 Tz (number ) Tj 2.508333 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 53.796296 Tz (poses ) Tj 1.925 0 Td 51.851852 Tz (\(500\) ) Tj 1.886111 0 Td 45.37037 Tz (to ) Tj 0.894444 0 Td 56.944444 Tz (improve ) Tj 51.428571 0 0 51.428571 0 1043.264151 Tm 25.316667 0 Td 51.851852 Tz (sampling. ) Tj 2.975 0 Td 55.840456 Tz (Conformations ) Tj 4.530556 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 50.555556 Tz (these ) Tj 1.633333 0 Td 51.851852 Tz (highly ) Tj 2.061111 0 Td 44.965278 Tz (flexible ) Tj 2.333333 0 Td 54.012346 Tz (molecules ) Tj 51.428571 0 0 51.428571 0 1003.945879 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.633333 0 Td 48.611111 Tz (also ) Tj 1.380556 0 Td 57.744108 Tz (precomputed ) Tj 4.005556 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 55.092593 Tz (absence ) Tj 2.527778 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 50.231481 Tz (receptor ) Tj 2.586111 0 Td 52.5 Tz (using ) Tj 51.428571 0 0 51.428571 0 959.361702 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 47.314815 Tz (stochastic ) Tj 2.994444 0 Td 52.546296 Tz (conformational ) Tj 4.569444 0 Td 50.771605 Tz (search ) Tj 1.983333 0 Td 51.851852 Tz (algorithm ) Tj 2.936111 0 Td 60.493827 Tz (and ) Tj 1.205556 0 Td 39.969136 Tz (all ) Tj 0.875 0 Td 51.311728 Tz (result ) Tj 51.428571 0 0 51.428571 0 919.606635 Tm 25.297222 0 Td 52.932099 Tz (ing ) Tj 1.069444 0 Td 53.596866 Tz (conformations ) Tj 4.316667 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 45.37037 Tz (rigidly ) Tj 2.061111 0 Td 57.79321 Tz (docked ) Tj 2.197222 0 Td 46.990741 Tz (into ) Tj 1.244444 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 46.090535 Tz (receptor. ) Tj 2.644444 0 Td 75.617284 Tz (Sub ) Tj 51.428571 0 0 51.428571 0 879.125471 Tm 25.316667 0 Td 43.209877 Tz (strate ) Tj 1.808333 0 Td 56.018519 Tz (docking ) Tj 2.605556 0 Td 47.685185 Tz (studies ) Tj 2.275 0 Td 59.143519 Tz (were ) Tj 1.633333 0 Td 56.893004 Tz (performed ) Tj 3.325 0 Td 45.37037 Tz (in ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.127778 0 Td 53.472222 Tz (presence ) Tj 2.819444 0 Td 59.41358 Tz (and ) Tj 51.428571 0 0 51.428571 0 834.424084 Tm 25.297222 0 Td 55.092593 Tz (absence ) Tj 2.605556 0 Td 58.333333 Tz (of ) Tj 0.913889 0 Td 55.092593 Tz (a ) Tj 0.622222 0 Td 44.290123 Tz (restraint ) Tj 2.702778 0 Td 48.971193 Tz (requiring ) Tj 2.955556 0 Td 55.092593 Tz (an ) Tj 0.952778 0 Td 51.388889 Tz (anionic ) Tj 2.469444 0 Td 59.953704 Tz (atom ) Tj 1.730556 0 Td 48.611111 Tz (to ) Tj 0.913889 0 Td 54.444444 Tz (occur ) Tj 58.571429 0 0 58.571429 0 793.060753 Tm 22.212195 0 Td 43.157182 Tz (inside ) Tj 1.639024 0 Td 45.528455 Tz (a ) Tj 0.392683 0 Td 44.579946 Tz (3.6 ) Tj 0.939024 0 Td 73.98374 Tz (A ) Tj 0.580488 0 Td 46.00271 Tz (sphere ) Tj 1.758537 0 Td 45.172764 Tz (centered ) Tj 2.270732 0 Td 45.528455 Tz (4.6 ) Tj 0.921951 0 Td 76.829268 Tz (A ) Tj 0.597561 0 Td 50.50813 Tz (from ) Tj 1.34878 0 Td 46.95122 Tz (both ) Tj 1.263415 0 Td 48.057814 Tz (metalions ) Tj 2.697561 0 Td 52.168022 Tz (and ) Tj 58.571429 0 0 58.571429 0 752.109375 Tm 22.212195 0 Td 43.631436 Tz (2.8 ) Tj 1.007317 0 Td 76.829268 Tz (A ) Tj 0.64878 0 Td 49.796748 Tz (from ) Tj 1.4 0 Td 44.579946 Tz (the ) Tj 0.973171 0 Td 52.168022 Tz (oxygen ) Tj 2.065854 0 Td 52.642276 Tz (atom ) Tj 1.468293 0 Td 49.796748 Tz (of ) Tj 0.7 0 Td 49.512195 Tz (T210. ) Tj 1.707317 0 Td 44.105691 Tz (In ) Tj 0.7 0 Td 35.094851 Tz (all ) Tj 0.836585 0 Td 41.260163 Tz (cases, ) Tj 1.690244 0 Td 44.579946 Tz (the ) Tj 0.939024 0 Td 49.796748 Tz (pose ) Tj 51.428571 0 0 51.428571 0 710.728395 Tm 25.277778 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 52.391975 Tz (lowest ) Tj 2.080556 0 Td 52.5 Tz (score ) Tj 1.730556 0 Td 46.018519 Tz (after ) Tj 1.555556 0 Td 50.084175 Tz (elimination ) Tj 3.519444 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 49.691358 Tz (ligand ) Tj 1.983333 0 Td 53.796296 Tz (poses ) Tj 1.866667 0 Td 53.472222 Tz (with ) Tj 51.428571 0 0 51.428571 0 668.148325 Tm 25.316667 0 Td 47.800926 Tz (strained ) Tj 2.469444 0 Td 53.596866 Tz (conformations ) Tj 4.375 0 Td 60.493827 Tz (was ) Tj 1.283333 0 Td 48.611111 Tz (selected ) Tj 2.508333 0 Td 48.611111 Tz (for ) Tj 1.011111 0 Td 48.611111 Tz (analysis ) Tj 2.488889 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 57.253086 Tz (discus ) Tj 27.142857 0 0 27.142857 0 634 Tm 47.968421 0 Td 105.921053 Tz (S1O. ) Tj 51.428571 0 0 51.428571 0 587.793282 Tm 26.016667 0 Td 53.472222 Tz (This ) Tj 1.497222 0 Td 77.777778 Tz (ATX ) Tj 1.633333 0 Td 45.37037 Tz (catalytic ) Tj 2.702778 0 Td 59.953704 Tz (domain ) Tj 2.391667 0 Td 61.574074 Tz (homology ) Tj 3.208333 0 Td 59.62963 Tz (model ) Tj 2.041667 0 Td 53.472222 Tz (was, ) Tj 1.516667 0 Td 48.070988 Tz (again, ) Tj 51.428571 0 0 51.428571 0 546.597813 Tm 25.277778 0 Td 51.041667 Tz (thus ) Tj 1.419444 0 Td 54.282407 Tz (used ) Tj 1.438889 0 Td 51.851852 Tz (as ) Tj 0.777778 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 56.018519 Tz (docking ) Tj 2.508333 0 Td 45.37037 Tz (target ) Tj 1.808333 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 46.990741 Tz (identify ) Tj 2.430556 0 Td 54.73251 Tz (promising ) Tj 3.130556 0 Td 51.131687 Tz (candidate ) Tj 51.428571 0 0 51.428571 0 505.33993 Tm 25.297222 0 Td 46.342593 Tz (inhibitors ) Tj 2.936111 0 Td 47.530864 Tz (for ) Tj 0.933333 0 Td 52.662037 Tz (experimental ) Tj 3.927778 0 Td 48.935185 Tz (Screening. ) Tj 3.091667 0 Td 40.740741 Tz (Initial ) Tj 1.847222 0 Td 48.611111 Tz (analysis ) Tj 2.469444 0 Td 54.62963 Tz (focused ) Tj 51.428571 0 0 51.428571 0 463.127811 Tm 25.297222 0 Td 59.953704 Tz (on ) Tj 0.855556 0 Td 50.462963 Tz (anionic ) Tj 2.236111 0 Td 55.092593 Tz (groups ) Tj 2.119444 0 Td 55.092593 Tz (such ) Tj 1.458333 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 51.851852 Tz (phosphate, ) Tj 3.247222 0 Td 44.155093 Tz (Sulfate, ) Tj 2.236111 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 51.262626 Tz (carboxylate ) Tj 51.428571 0 0 51.428571 0 420.520833 Tm 25.297222 0 Td 50.231481 Tz (as ) Tj 0.933333 0 Td 51.851852 Tz (well ) Tj 1.555556 0 Td 50.231481 Tz (as ) Tj 0.952778 0 Td 47.530864 Tz (bioisosteres ) Tj 3.772222 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 50.555556 Tz (these ) Tj 1.808333 0 Td 51.388889 Tz (anionic ) Tj 2.488889 0 Td 55.092593 Tz (groups ) Tj 2.333333 0 Td 50.411523 Tz (including ) Tj 51.428571 0 0 51.428571 0 380.733496 Tm 25.297222 0 Td 56.944444 Tz (phosphonamide, ) Tj 5.172222 0 Td 52.391975 Tz (Sulfonamide, ) Tj 4.141667 0 Td 59.41358 Tz (and ) Tj 1.458333 0 Td 51.419753 Tz (oxocarboxylate. ) Tj 5.036111 0 Td 91.820988 Tz (Com ) Tj 51.428571 0 0 51.428571 0 337.640587 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.275 0 Td 57.87037 Tz (showing ) Tj 2.547222 0 Td 47.530864 Tz (better ) Tj 1.847222 0 Td 51.041667 Tz (than ) Tj 1.4 0 Td 72.376543 Tz (50% ) Tj 1.438889 0 Td 77.777778 Tz (ATX ) Tj 1.536111 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 45.37037 Tz (at ) Tj 0.758333 0 Td 56.712963 Tz (10 ) Tj 0.836111 0 Td 81.018519 Tz (uM ) Tj 1.108333 0 Td 61.574074 Tz (by ) Tj 51.428571 0 0 51.428571 0 298.392157 Tm 25.297222 0 Td 63.194444 Tz (enzyme ) Tj 2.430556 0 Td 44.965278 Tz (activity ) Tj 2.352778 0 Td 51.851852 Tz (assay ) Tj 1.75 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 55.902778 Tz (used ) Tj 1.497222 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 46.342593 Tz (similarity ) Tj 2.955556 0 Td 45.833333 Tz (targets ) Tj 2.119444 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 69.135802 Tz (Sub ) Tj 51.428571 0 0 51.428571 0 255.199005 Tm 25.316667 0 Td 52.777778 Tz (sequent ) Tj 2.488889 0 Td 48.971193 Tz (analyses. ) Tj 2.975 0 Td 50.673401 Tz (Ninety-five ) Tj 3.636111 0 Td 46.666667 Tz (structures ) Tj 3.130556 0 Td 59.143519 Tz (were ) Tj 1.730556 0 Td 48.611111 Tz (selected ) Tj 2.644444 0 Td 48.611111 Tz (for ) Tj 51.428571 0 0 51.428571 0 214.274809 Tm 25.316667 0 Td 51.131687 Tz (screening ) Tj 3.052778 0 Td 51.851852 Tz (out ) Tj 1.186111 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 61.574074 Tz (500 ) Tj 1.361111 0 Td 61.934156 Tz (compounds ) Tj 3.655556 0 Td 57.79321 Tz (docked ) Tj 2.372222 0 Td 49.074074 Tz (against ) Tj 2.352778 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 170.682809 Tm 25.297222 0 Td 45.37037 Tz (catalytic ) Tj 2.663889 0 Td 59.953704 Tz (domain ) Tj 2.352778 0 Td 61.168981 Tz (homology ) Tj 3.169444 0 Td 54.012346 Tz (model. ) Tj 2.177778 0 Td 35.648148 Tz (It ) Tj 0.602778 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 54.552469 Tz (demonstrated ) Tj 4.102778 0 Td 46.180556 Tz (that ) Tj ET Q endstream endobj 124 0 obj << /Length 1 >> stream q endstream endobj 125 0 obj << /Length 17277 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,969,590 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 51.428571 0 0 51.428571 0 2968 Tm 14.875 0 Td 77.777778 Tz (7 ) Tj 40 0 0 40 0 2921 Tm 8.25 0 Td 70.833333 Tz (19 ) Tj 1.175 0 Td 72.916667 Tz (of ) Tj 1.1 0 Td 62.5 Tz (the ) Tj 1.4 0 Td 75 Tz (95 ) Tj 1.25 0 Td 60 Tz (structures ) Tj 3.95 0 Td 60.648148 Tz (inhibited ) Tj 3.625 0 Td 91.666667 Tz (20% ) Tj 1.975 0 Td 68.75 Tz (or ) Tj 1.15 0 Td 78.125 Tz (more ) Tj 2.175 0 Td 72.916667 Tz (of ) Tj 1.05 0 Td 65.277778 Tz (the ) Tj 1.425 0 Td 116.666667 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2872.788732 Tm 6.358333 0 Td 50.771605 Tz (catalyzed ) Tj 2.897222 0 Td 55.902778 Tz (FS-3 ) Tj 1.477778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.15 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 74.537037 Tz (10LM ) Tj 1.866667 0 Td 49.074074 Tz (concentration. ) Tj 4.238889 0 Td 54.282407 Tz (This ) Tj 1.419444 0 Td 56.388889 Tz (selec ) Tj 51.428571 0 0 51.428571 0 2828.461538 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.4 0 Td 51.851852 Tz (process ) Tj 2.430556 0 Td 61.574074 Tz (was ) Tj 1.361111 0 Td 48.971193 Tz (therefore ) Tj 2.897222 0 Td 72.376543 Tz (20% ) Tj 1.555556 0 Td 51.041667 Tz (accurate ) Tj 2.722222 0 Td 43.75 Tz (in ) Tj 0.816667 0 Td 47.530864 Tz (selecting ) Tj 2.8 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 2784.705882 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.294444 0 Td 51.851852 Tz (with ) Tj 1.458333 0 Td 64.814815 Tz (some ) Tj 1.730556 0 Td 53.472222 Tz (degree ) Tj 2.080556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 45.075758 Tz (inhibition. ) Tj 51.428571 0 0 51.428571 0 2743.034869 Tm 7.116667 0 Td 58.796296 Tz (Docking ) Tj 2.644444 0 Td 47.685185 Tz (studies ) Tj 2.177778 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 1.555556 0 Td 45.37037 Tz (catalytic ) Tj 2.625 0 Td 59.953704 Tz (domain ) Tj 2.333333 0 Td 61.574074 Tz (homology ) Tj 51.428571 0 0 51.428571 0 2700.125891 Tm 6.358333 0 Td 59.62963 Tz (model ) Tj 1.963889 0 Td 58.333333 Tz (were ) Tj 1.516667 0 Td 51.041667 Tz (able ) Tj 1.341667 0 Td 46.990741 Tz (to ) Tj 0.680556 0 Td 53.240741 Tz (provide ) Tj 2.352778 0 Td 47.685185 Tz (insight ) Tj 2.138889 0 Td 45.37037 Tz (into ) Tj 1.205556 0 Td 44.965278 Tz (activity ) Tj 2.313889 0 Td 48.611111 Tz (differences ) Tj 3.344444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2657.67929 Tm 6.358333 0 Td 52.662037 Tz (very ) Tj 1.419444 0 Td 48.611111 Tz (similar ) Tj 2.119444 0 Td 45.37037 Tz (structures. ) Tj 3.130556 0 Td 55.902778 Tz (Very ) Tj 1.477778 0 Td 48.287037 Tz (Surprising ) Tj 3.013889 0 Td 44.907407 Tz (results ) Tj 2.022222 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 48.611111 Tz (noted, ) Tj 1.905556 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 2617.06 Tm 6.358333 0 Td 54.282407 Tz (example, ) Tj 2.916667 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 58.333333 Tz (two ) Tj 1.322222 0 Td 46.090535 Tz (different ) Tj 2.741667 0 Td 49.331276 Tz (isoindole ) Tj 2.916667 0 Td 61.934156 Tz (compounds ) Tj 3.636111 0 Td 45.37037 Tz (that ) Tj 1.322222 0 Td 58.333333 Tz (dif ) Tj 51.428571 0 0 51.428571 0 2576.500736 Tm 6.358333 0 Td 49.907407 Tz (fered ) Tj 1.672222 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 48.611111 Tz (location ) Tj 2.527778 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 52.662037 Tz (carboxyl ) Tj 2.702778 0 Td 55.555556 Tz (pendant ) Tj 2.508333 0 Td 51.311728 Tz (group: ) Tj 31.428571 0 0 31.428571 0 2383.522727 Tm 17.786364 0 Td 111.363636 Tz (O ) Tj 14.031818 0 Td 121.969697 Tz (N ) Tj 41.428571 0 0 41.428571 0 2357.957746 Tm 19.165517 0 Td 84.482759 Tz (O ) Tj 5.551724 0 Td 100.574713 Tz (SN ) Tj 31.428571 0 0 31.428571 0 2296 Tm 15.622727 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 2267 Tm 25.422727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2156.896552 Tm 10.754545 0 Td 106.060606 Tz (HO ) Tj 14.509091 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2063 Tm 12.981818 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2012 Tm 22.972727 0 Td 76.515152 Tz (5564949 ) Tj 31.428571 0 0 31.428571 0 1833 Tm 14.922727 0 Td 111.363636 Tz (O ) Tj 16.1 0 Td 121.969697 Tz (N ) Tj 28.571429 0 0 28.571429 0 1821 Tm 35 0 Td 90.416667 Tz (S. ) Tj 40.714286 0 0 40.714286 0 1802.111111 Tm 18.126316 0 Td 85.964912 Tz (O ) Tj 6.336842 0 Td 122.807018 Tz (NN ) Tj 31.428571 0 0 31.428571 0 1733 Tm 12.504545 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 1699 Tm 23.672727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 1587 Tm 23.481818 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1432 Tm 10.627273 0 Td 106.060606 Tz (HO ) Tj 4.295455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1380 Tm 23.036364 0 Td 76.515152 Tz (5564676 ) Tj 51.428571 0 0 51.428571 0 1167.54902 Tm 7.097222 0 Td 63.734568 Tz (The ) Tj 1.244444 0 Td 60.185185 Tz (5564949 ) Tj 2.663889 0 Td 64.00463 Tz (compound ) Tj 3.169444 0 Td 50.411523 Tz (exhibited ) Tj 2.819444 0 Td 58.333333 Tz (a ) Tj 0.447222 0 Td 74.537037 Tz (51% ) Tj 1.477778 0 Td 50.771605 Tz (reduction ) Tj 2.838889 0 Td 46.990741 Tz (in ) Tj 0.661111 0 Td 77.777778 Tz (ATX ) Tj 48.571429 0 0 48.571429 0 1126 Tm 6.732353 0 Td 49.754902 Tz (inhibition ) Tj 3.5 0 Td 46.323529 Tz (at ) Tj 1.132353 0 Td 60.04902 Tz (10 ) Tj 1.194118 0 Td 61.764706 Tz (micromole ) Tj 3.829412 0 Td 51.960784 Tz (concentration, ) Tj 4.879412 0 Td 59.803922 Tz (whereas ) Tj 3.026471 0 Td 52.614379 Tz (the ) Tj 51.428571 0 0 51.428571 0 1084.554736 Tm 6.377778 0 Td 59.722222 Tz (5564676 ) Tj 2.702778 0 Td 64.00463 Tz (compound ) Tj 3.247222 0 Td 61.033951 Tz (showed ) Tj 2.411111 0 Td 56.712963 Tz (no ) Tj 0.894444 0 Td 50.411523 Tz (reduction ) Tj 2.916667 0 Td 45.910494 Tz (levels ) Tj 1.827778 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 41.049383 Tz (all ) Tj 0.933333 0 Td 44.290123 Tz (\(at ) Tj 0.952778 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1042.449344 Tm 6.377778 0 Td 61.574074 Tz (same ) Tj 1.672222 0 Td 48.179012 Tz (concentration\). ) Tj 4.511111 0 Td 55.092593 Tz (Thus, ) Tj 1.847222 0 Td 44.781145 Tz (selectivity ) Tj 3.130556 0 Td 57.87037 Tz (between ) Tj 2.625 0 Td 46.759259 Tz (certain ) Tj 2.158333 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1001.223529 Tm 6.358333 0 Td 54.166667 Tz (pounds, ) Tj 2.741667 0 Td 56.893004 Tz (sometimes ) Tj 3.519444 0 Td 46.990741 Tz (constitutional ) Tj 4.394444 0 Td 53.703704 Tz (isomers ) Tj 2.663889 0 Td 51.851852 Tz (even, ) Tj 2.002778 0 Td 60.493827 Tz (was ) Tj 1.555556 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 959.265589 Tm 6.377778 0 Td 49.331276 Tz (necessity ) Tj 2.780556 0 Td 45.37037 Tz (to ) Tj 0.661111 0 Td 54.372428 Tz (determine ) Tj 3.013889 0 Td 46.8107 Tz (effective ) Tj 2.625 0 Td 53.009259 Tz (ATXinhibitors. ) Tj 4.55 0 Td 65.895062 Tz (The ) Tj 1.283333 0 Td 60.185185 Tz (5564949 ) Tj 51.428571 0 0 51.428571 0 920.758918 Tm 6.358333 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 47.800926 Tz (actually ) Tj 2.488889 0 Td 61.574074 Tz (was ) Tj 1.322222 0 Td 56.388889 Tz (found ) Tj 1.886111 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 49.074074 Tz (display ) Tj 2.255556 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 62.114198 Tz (number ) Tj 2.391667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 57.685185 Tz (favor ) Tj 51.428571 0 0 51.428571 0 876.352406 Tm 6.358333 0 Td 51.041667 Tz (able ) Tj 1.516667 0 Td 46.990741 Tz (interactions ) Tj 3.675 0 Td 46.990741 Tz (in ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 58.333333 Tz (docked ) Tj 2.372222 0 Td 60.185185 Tz (complex ) Tj 2.819444 0 Td 45.37037 Tz (in ) Tj 0.855556 0 Td 53.796296 Tz (terms ) Tj 1.886111 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 834.415758 Tm 6.358333 0 Td 43.013468 Tz (reactivity. ) Tj 3.072222 0 Td 59.62963 Tz (These ) Tj 2.022222 0 Td 46.990741 Tz (interactions ) Tj 3.655556 0 Td 50.462963 Tz (include ) Tj 2.372222 0 Td 55.092593 Tz (a ) Tj 0.563889 0 Td 45.010288 Tz (cation-It ) Tj 2.663889 0 Td 47.727273 Tz (interaction ) Tj 51.428571 0 0 51.428571 0 794.53706 Tm 6.338889 0 Td 57.87037 Tz (between ) Tj 2.605556 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 51.262626 Tz (carboxylate ) Tj 3.558333 0 Td 48.935185 Tz (functional ) Tj 3.111111 0 Td 56.388889 Tz (group ) Tj 1.866667 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 57.037037 Tz (R284, ) Tj 1.866667 0 Td 58.333333 Tz (an ) Tj 0.913889 0 Td 63.734568 Tz (ion ) Tj 51.428571 0 0 51.428571 0 753.467609 Tm 6.358333 0 Td 49.074074 Tz (pairing ) Tj 2.216667 0 Td 46.843434 Tz (interaction ) Tj 3.247222 0 Td 57.87037 Tz (between ) Tj 2.586111 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 51.557239 Tz (carboxylate ) Tj 3.558333 0 Td 48.611111 Tz (functional ) Tj 3.091667 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 710.1133 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 56.388889 Tz (R285, ) Tj 1.886111 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 52.5 Tz (metal ) Tj 1.788889 0 Td 45.775463 Tz (ligating ) Tj 2.391667 0 Td 46.990741 Tz (interactions ) Tj 3.597222 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 49.691358 Tz (isoindole ) Tj 51.428571 0 0 51.428571 0 668.129771 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.361111 0 Td 49.331276 Tz (diazerine ) Tj 2.975 0 Td 48.935185 Tz (functional ) Tj 3.208333 0 Td 51.388889 Tz (groups. ) Tj 2.508333 0 Td 48.611111 Tz (In ) Tj 0.894444 0 Td 45.730453 Tz (contrast, ) Tj 2.780556 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 60.185185 Tz (5564676 ) Tj 51.428571 0 0 51.428571 0 628.409756 Tm 6.358333 0 Td 45.910494 Tz (failed ) Tj 1.788889 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 59.953704 Tz (dock ) Tj 1.555556 0 Td 46.990741 Tz (into ) Tj 1.283333 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 76.697531 Tz (ATX ) Tj 1.555556 0 Td 44.650206 Tz (catalytic ) Tj 2.625 0 Td 59.41358 Tz (domain ) Tj 2.352778 0 Td 54.012346 Tz (model, ) Tj 2.138889 0 Td 56.944444 Tz (Suggest ) Tj 51.428571 0 0 51.428571 0 585.307985 Tm 6.358333 0 Td 50.771605 Tz (ing ) Tj 1.186111 0 Td 46.180556 Tz (that ) Tj 1.361111 0 Td 45.37037 Tz (insufficient ) Tj 3.538889 0 Td 53.148148 Tz (space ) Tj 1.886111 0 Td 61.574074 Tz (was ) Tj 1.341667 0 Td 48.611111 Tz (available ) Tj 2.897222 0 Td 47.530864 Tz (for ) Tj 1.069444 0 Td 44.560185 Tz (this ) Tj 1.361111 0 Td 51.851852 Tz (molecule. ) Tj 51.428571 0 0 51.428571 0 544.6399 Tm 6.377778 0 Td 52.175926 Tz (Relocation ) Tj 3.402778 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 51.557239 Tz (carboxylate ) Tj 3.655556 0 Td 57.037037 Tz (group ) Tj 1.983333 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 60.185185 Tz (5564949 ) Tj 2.780556 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 505.654367 Tm 6.358333 0 Td 60.925926 Tz (pound ) Tj 1.983333 0 Td 57.523148 Tz (from ) Tj 1.536111 0 Td 51.851852 Tz (the ) Tj 1.088889 0 Td 58.333333 Tz (meta ) Tj 1.536111 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 52.662037 Tz (para ) Tj 1.380556 0 Td 49.421296 Tz (position ) Tj 2.547222 0 Td 51.041667 Tz (Suggests ) Tj 2.605556 0 Td 45.37037 Tz (that ) Tj 1.225 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 53.472222 Tz (very ) Tj 51.428571 0 0 51.428571 0 460.793264 Tm 6.358333 0 Td 46.450617 Tz (close, ) Tj 1.788889 0 Td 48.112536 Tz (energetically ) Tj 3.888889 0 Td 52.146465 Tz (unfavorable ) Tj 3.597222 0 Td 46.548822 Tz (interaction ) Tj 3.208333 0 Td 61.574074 Tz (would ) Tj 1.944444 0 Td 55.092593 Tz (occur ) Tj 1.75 0 Td 54.282407 Tz (with ) Tj 40 0 0 40 0 426 Tm 8.15 0 Td 65.277778 Tz (the ) Tj 1.4 0 Td 75 Tz (backbone ) Tj 3.85 0 Td 70.833333 Tz (of ) Tj 1.025 0 Td 72.5 Tz (R284. ) Tj 2.4 0 Td 75.833333 Tz (These ) Tj 2.525 0 Td 73.611111 Tz (models ) Tj 2.9 0 Td 63.888889 Tz (are ) Tj 1.375 0 Td 62.5 Tz (consistent ) Tj 4 0 Td 67.708333 Tz (with ) Tj 1.875 0 Td 63.888889 Tz (the ) Tj 51.428571 0 0 51.428571 0 378.615187 Tm 6.358333 0 Td 49.259259 Tz (difference ) Tj 3.247222 0 Td 45.37037 Tz (in ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 1.166667 0 Td 43.981481 Tz (ability ) Tj 2.158333 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 48.611111 Tz (the ) Tj 1.225 0 Td 60.185185 Tz (5564949 ) Tj 2.819444 0 Td 64.409722 Tz (compound ) Tj 3.383333 0 Td 55.740741 Tz (\(meta ) Tj 51.428571 0 0 51.428571 0 337.294118 Tm 6.358333 0 Td 53.240741 Tz (isomer\) ) Tj 2.411111 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 60.185185 Tz (5564676 ) Tj 2.741667 0 Td 63.599537 Tz (compound ) Tj 3.247222 0 Td 49.907407 Tz (\(para ) Tj 1.711111 0 Td 52.314815 Tz (isomer\) ) Tj 2.391667 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 44.907407 Tz (inhibit ) Tj 38.571429 0 0 38.571429 0 301 Tm 8.503704 0 Td 86.419753 Tz (ATX. ) Tj 51.428571 0 0 51.428571 0 254.053763 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.380556 0 Td 41.319444 Tz (full ) Tj 1.244444 0 Td 51.851852 Tz (breadth ) Tj 2.430556 0 Td 58.333333 Tz (of ) Tj 0.875 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 45.37037 Tz (specific ) Tj 2.469444 0 Td 61.934156 Tz (compounds ) Tj 3.616667 0 Td 45.37037 Tz (that ) Tj 1.341667 0 Td 60.493827 Tz (met ) Tj 1.361111 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 215.404101 Tm 6.358333 0 Td 77.777778 Tz (ATX ) Tj 1.633333 0 Td 46.666667 Tz (inhibition ) Tj 3.013889 0 Td 52.391975 Tz (requirements ) Tj 3.966667 0 Td 53.703704 Tz (through ) Tj 2.488889 0 Td 42.939815 Tz (this ) Tj 1.283333 0 Td 55.902778 Tz (modeling ) Tj 2.897222 0 Td 51.851852 Tz (process ) Tj 51.428571 0 0 51.428571 0 170.674095 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 48.611111 Tz (further ) Tj 2.177778 0 Td 48.611111 Tz (analysis ) Tj 2.527778 0 Td 51.851852 Tz (were: ) Tj 31.428571 0 0 31.428571 0 2868 Tm 68.822727 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 2775 Tm 62.490909 0 Td 90.151515 Tz (H ) Tj 137.142857 0 0 137.142857 0 2654 Tm 11.272917 0 Td 24.305556 Tz (\( ) Tj 0.714583 0 Td 52.662037 Tz (\)-\( ) Tj 1.421875 0 Td 53.472222 Tz (\)-\( ) Tj 49.285714 0 0 49.285714 0 2642.113402 Tm 35.426087 0 Td 104.830918 Tz (\\ ) Tj 1.805797 0 Td 104.830918 Tz (/ ) Tj 2.637681 0 Td 47.342995 Tz (S ) Tj 4.017391 0 Td 71.014493 Tz (C ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 31.428571 0 0 31.428571 0 2421 Tm 54.027273 0 Td 76.515152 Tz (7905958 ) Tj 31.428571 0 0 31.428571 0 2364 Tm 44.672727 0 Td 111.363636 Tz (OH ) Tj 21.254545 0 Td 111.363636 Tz (O ) Tj 39.52381 0 0 39.52381 0 2322.006849 Tm 31.626506 0 Td 54.819277 Tz (15 ) Tj 2.024096 0 Td 71.686747 Tz (O ) Tj 5.161446 0 Td 88.554217 Tz (O ) Tj 5.161446 0 Td 88.554217 Tz (O ) Tj 5.161446 0 Td 88.554217 Tz (O ) Tj 5.186747 0 Td 84.337349 Tz (OH ) Tj 230 0 0 230 0 2170 Tm 6.982609 0 Td 84.541063 Tz (oo: ) Tj 40.571429 0 0 40.571429 0 2140.775862 Tm 31.105634 0 Td 49.295775 Tz (o ) Tj 1.158451 0 Td 84.213615 Tz (HO ) Tj 5.545775 0 Td 86.267606 Tz (O ) Tj 10.056338 0 Td 86.267606 Tz (O ) Tj 5.052817 0 Td 86.267606 Tz (O ) Tj 31.428571 0 0 31.428571 0 2103 Tm 44.672727 0 Td 111.363636 Tz (O ) Tj 20.65 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2052 Tm 54.409091 0 Td 77.272727 Tz (5186522 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30.714286 0 0 30.714286 0 1309.022901 Tm 40.6 0 Td 81.395349 Tz (40 ) Tj 14.683721 0 Td 78.294574 Tz (7839888 ) Tj 31.428571 0 0 31.428571 0 1255 Tm 65.959091 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1212 Tm 68.345455 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1126.666667 Tm 48.809091 0 Td 111.363636 Tz (O ) Tj 6.490909 0 Td 111.363636 Tz (O ) Tj 6.490909 0 Td 111.363636 Tz (O ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 140 0 0 140 0 999 Tm 10.935714 0 Td 126.190476 Tz (KOCO ) Tj 31.428571 0 0 31.428571 0 952 Tm 48.809091 0 Td 111.363636 Tz (O ) Tj 12.981818 0 Td 111.363636 Tz (O ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 31.428571 0 0 31.428571 0 862 Tm 41.65 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 819 Tm 44.672727 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 770 Tm 54.409091 0 Td 76.515152 Tz (5761473 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 21.428571 0 0 21.428571 0 627 Tm 93.333333 0 Td 89.444444 Tz (Sa ) Tj 31.428571 0 0 31.428571 0 635 Tm 48.745455 0 Td 111.363636 Tz (O ) Tj 14.063636 0 Td 121.969697 Tz (N ) Tj 37.142857 0 0 37.142857 0 608.876712 Tm 47.6 0 Td 94.230769 Tz (O ) Tj 6.138462 0 Td 116.666667 Tz (nN ) Tj 31.428571 0 0 31.428571 0 548 Tm 46.613636 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 519 Tm 56.413636 0 Td 121.969697 Tz (N ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 31.428571 0 0 31.428571 0 408.540984 Tm 41.745455 0 Td 106.060606 Tz (HO ) Tj 14.509091 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 315 Tm 43.940909 0 Td 111.363636 Tz (O ) Tj 30.714286 0 0 30.714286 0 262.15625 Tm 40.665116 0 Td 73.255814 Tz (65 ) Tj 14.553488 0 Td 78.294574 Tz (5564949 ) Tj 1.428571 0 0 1.428571 0 2018 Tm 941.5 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 126 0 obj << /Length 1 >> stream q endstream endobj 127 0 obj << /Length 36085 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,969,590 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.472973 0 Td 72.522523 Tz (9 ) Tj 40 0 0 40 0 2913 Tm 17.475 0 Td 67.083333 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2828 Tm 10.563636 0 Td 121.969697 Tz (N ) Tj 71.428571 0 0 71.428571 0 2741 Tm 15.54 0 Td 60.666667 Tz (/ ) Tj 0.924 0 Td 58.333333 Tz (\\ ) Tj 33.333333 0 0 33.333333 0 2698.666667 Tm 16.83 0 Td 105 Tz (O ) Tj 12.15 0 Td 105 Tz (O ) Tj 1.62 0 Td 105 Tz (O ) Tj 31.428571 0 0 31.428571 0 2645 Tm 23.418182 0 Td 78.030303 Tz (5538444 ) Tj 31.428571 0 0 31.428571 0 2556 Tm 37.290909 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 2499 Tm 27.713636 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2441 Tm 30.895455 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2428.219512 Tm 22.240909 0 Td 111.363636 Tz (O ) Tj 8.75 0 Td 106.060606 Tz (H ) Tj 31.428571 0 0 31.428571 0 2326 Tm 22.4 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2292 Tm 11.2 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2214 Tm 22.240909 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2192 Tm 13.65 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2122 Tm 23.036364 0 Td 72.474747 Tz (571 ) Tj 1.463636 0 Td 71.590909 Tz (1925 ) Tj 31.428571 0 0 31.428571 0 2082 Tm 12.377273 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1982 Tm 21.572727 0 Td 111.363636 Tz (O ) Tj 55.357143 0 0 55.357143 0 1897.246377 Tm 11.651613 0 Td 221.290323 Tz (1- ) Tj 2.727742 0 Td 42.150538 Tz (S ) Tj 2.023226 0 Td 69.247312 Tz (N ) Tj 2.095484 0 Td 69.247312 Tz (N ) Tj 36.190476 0 0 36.190476 0 1885.115385 Tm 17.103947 0 Td 105.921053 Tz (N ) Tj 6.852632 0 Td 92.105263 Tz (21 ) Tj 3.205263 0 Td 94.407895 Tz (21 ) Tj 31.428571 0 0 31.428571 0 1860 Tm 19.790909 0 Td 106.060606 Tz (H ) Tj 39.285714 0 0 39.285714 0 1804.539474 Tm 21.636364 0 Td 97.575758 Tz (N ) Tj 3.385455 0 Td 224.848485 Tz (N ) Tj 83.571429 0 0 83.571429 0 1721.865672 Tm 9.584615 0 Td 91.737892 Tz (r ) Tj 1.280342 0 Td 41.880342 Tz (O ) Tj 31.428571 0 0 31.428571 0 1667 Tm 23.036364 0 Td 66.287879 Tz (79.21385 ) Tj 31.428571 0 0 31.428571 0 1625 Tm 12.377273 0 Td 111.363636 Tz (OH ) Tj 13.395455 0 Td 111.363636 Tz (O ) Tj 124.285714 0 0 124.285714 0 1461.756522 Tm 2.703448 0 Td 28.16092 Tz (O ) Tj 2.631034 0 Td 140.804598 Tz (O ) Tj 1.697701 0 Td 139.463602 Tz (O ) Tj 31.428571 0 0 31.428571 0 1445 Tm 19.090909 0 Td 111.363636 Tz (O ) Tj 15.018182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1377 Tm 31.468182 0 Td 121.969697 Tz (N ) Tj 109.52381 0 0 109.52381 0 1298.96 Tm 8.080435 0 Td 31.956522 Tz (O ) Tj 1.89 0 Td 41.086957 Tz (\( ) Tj 0.84 0 Td 41.086957 Tz (\) ) Tj 31.428571 0 0 31.428571 0 1165 Tm 23.195455 0 Td 77.272727 Tz (5210574 ) Tj 51.428571 0 0 51.428571 0 1049.790427 Tm 7.097222 0 Td 66.435185 Tz (As ) Tj 1.030556 0 Td 51.851852 Tz (alluded ) Tj 2.411111 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 52.391975 Tz (above, ) Tj 2.138889 0 Td 50.555556 Tz (these ) Tj 1.730556 0 Td 62.294239 Tz (compounds ) Tj 3.636111 0 Td 59.953704 Tz (were ) Tj 1.691667 0 Td 54.768519 Tz (determined ) Tj 51.428571 0 0 51.428571 0 1010.172781 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.469444 0 Td 55.555556 Tz (docking ) Tj 2.508333 0 Td 47.685185 Tz (studies ) Tj 2.197222 0 Td 58.333333 Tz (which ) Tj 1.925 0 Td 48.341049 Tz (additionally ) Tj 3.636111 0 Td 54.282407 Tz (provided ) Tj 2.780556 0 Td 47.222222 Tz (insight ) Tj 51.428571 0 0 51.428571 0 962.597156 Tm 6.358333 0 Td 46.990741 Tz (into ) Tj 1.283333 0 Td 52.824074 Tz (unforeseen ) Tj 3.325 0 Td 52.777778 Tz (binding ) Tj 2.391667 0 Td 56.17284 Tz (modes. ) Tj 2.158333 0 Td 63.734568 Tz (The ) Tj 1.302778 0 Td 59.722222 Tz (7839888 ) Tj 2.644444 0 Td 64.814815 Tz (compound ) Tj 3.247222 0 Td 61.574074 Tz (was ) Tj 40 0 0 40 0 925 Tm 8.2 0 Td 62.5 Tz (selected ) Tj 3.3 0 Td 62.5 Tz (for ) Tj 1.4 0 Td 58.333333 Tz (in ) Tj 1.025 0 Td 55.555556 Tz (silico ) Tj 2.325 0 Td 63.75 Tz (evaluation ) Tj 4.15 0 Td 77.083333 Tz (on ) Tj 1.25 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 62.5 Tz (basis ) Tj 2.225 0 Td 70.833333 Tz (of ) Tj 1.075 0 Td 62.5 Tz (the ) Tj 1.45 0 Td 77.777778 Tz (oxocar ) Tj 51.428571 0 0 51.428571 0 878.603513 Tm 6.338889 0 Td 52.662037 Tz (boxylate ) Tj 2.8 0 Td 48.935185 Tz (functional ) Tj 3.208333 0 Td 52.391975 Tz (group, ) Tj 2.177778 0 Td 58.333333 Tz (which ) Tj 2.041667 0 Td 61.574074 Tz (was ) Tj 1.4 0 Td 53.472222 Tz (expected ) Tj 2.838889 0 Td 45.37037 Tz (to ) Tj 0.855556 0 Td 45.37037 Tz (interact ) Tj 51.428571 0 0 51.428571 0 834.401242 Tm 6.358333 0 Td 50.771605 Tz (favorably ) Tj 2.955556 0 Td 53.472222 Tz (with ) Tj 1.497222 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 48.070988 Tz (active ) Tj 1.925 0 Td 42.12963 Tz (site ) Tj 1.225 0 Td 53.148148 Tz (metal ) Tj 1.808333 0 Td 45.37037 Tz (ions. ) Tj 1.536111 0 Td 64.814815 Tz (The ) Tj 1.380556 0 Td 49.016204 Tz (thiourea ) Tj 2.547222 0 Td 64.00463 Tz (func ) Tj 51.428571 0 0 51.428571 0 795.203956 Tm 6.338889 0 Td 46.450617 Tz (tional ) Tj 1.827778 0 Td 57.037037 Tz (group ) Tj 1.925 0 Td 55.092593 Tz (of ) Tj 0.758333 0 Td 43.75 Tz (this ) Tj 1.225 0 Td 63.599537 Tz (compound ) Tj 3.266667 0 Td 62.654321 Tz (was ) Tj 1.302778 0 Td 56.388889 Tz (found ) Tj 1.866667 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 50.462963 Tz (involve ) Tj 2.275 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 51.203704 Tz (ligat ) Tj 51.428571 0 0 51.428571 0 750.471769 Tm 6.358333 0 Td 50.771605 Tz (ing ) Tj 1.127778 0 Td 57.253086 Tz (one ) Tj 1.205556 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 48.070988 Tz (active ) Tj 1.925 0 Td 41.319444 Tz (site ) Tj 1.186111 0 Td 52.5 Tz (metal ) Tj 1.788889 0 Td 44.722222 Tz (ions. ) Tj 1.536111 0 Td 53.472222 Tz (This ) Tj 1.497222 0 Td 46.548822 Tz (interaction ) Tj 3.266667 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 711.468085 Tm 6.358333 0 Td 44.871795 Tz (electrostatic ) Tj 3.713889 0 Td 46.720679 Tz (interactions ) Tj 3.538889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 51.262626 Tz (carboxylate ) Tj 3.597222 0 Td 48.611111 Tz (functional ) Tj 3.091667 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 669.542714 Tm 6.338889 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 60.763889 Tz (8284 ) Tj 1.691667 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 64.814815 Tz (K249 ) Tj 1.769444 0 Td 50.771605 Tz (are ) Tj 1.127778 0 Td 45.37037 Tz (likely ) Tj 1.886111 0 Td 49.789562 Tz (responsible ) Tj 3.519444 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 46.450617 Tz (resultant ) Tj 51.428571 0 0 51.428571 0 627.693069 Tm 6.377778 0 Td 72.376543 Tz (59% ) Tj 1.516667 0 Td 77.777778 Tz (ATX ) Tj 1.691667 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 51.49177 Tz (observed. ) Tj 3.013889 0 Td 64.814815 Tz (The ) Tj 1.4 0 Td 51.203704 Tz (other ) Tj 1.75 0 Td 61.574074 Tz (compounds ) Tj 3.636111 0 Td 58.333333 Tz (were ) Tj 48.571429 0 0 48.571429 0 586 Tm 6.732353 0 Td 60.392157 Tz (found ) Tj 2.038235 0 Td 48.039216 Tz (to ) Tj 0.864706 0 Td 61.764706 Tz (meet ) Tj 1.729412 0 Td 51.470588 Tz (the ) Tj 1.173529 0 Td 52.941176 Tz (desired ) Tj 2.408824 0 Td 83.496732 Tz (ATX ) Tj 1.75 0 Td 49.754902 Tz (inhibition ) Tj 3.232353 0 Td 48.611111 Tz (levels ) Tj 2.017647 0 Td 51.470588 Tz (as ) Tj 0.905882 0 Td 49.411765 Tz (well, ) Tj 1.708824 0 Td 54.901961 Tz (as ) Tj 51.428571 0 0 51.428571 0 546.96861 Tm 6.358333 0 Td 53.877315 Tz (provided ) Tj 2.761111 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 58.333333 Tz (Examples ) Tj 2.994444 0 Td 51.851852 Tz (below. ) Tj 51.428571 0 0 51.428571 0 505.056628 Tm 7.116667 0 Td 50.87963 Tz (Previously ) Tj 3.325 0 Td 49.826389 Tz (reported ) Tj 2.566667 0 Td 77.777778 Tz (ATX ) Tj 1.613889 0 Td 46.342593 Tz (inhibitors ) Tj 2.994444 0 Td 50.771605 Tz (are ) Tj 1.108333 0 Td 41.049383 Tz (all ) Tj 0.952778 0 Td 52.777778 Tz (analogs ) Tj 2.411111 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 462.506053 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.605556 0 Td 50.231481 Tz (product, ) Tj 2.605556 0 Td 60.763889 Tz (LPA, ) Tj 1.594444 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 40.509259 Tz (fail ) Tj 1.108333 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 59.143519 Tz (meet ) Tj 1.575 0 Td 58.333333 Tz (most ) Tj 1.575 0 Td 50.462963 Tz (metrics ) Tj 2.275 0 Td 51.851852 Tz (applied ) Tj 51.428571 0 0 51.428571 0 420.014458 Tm 6.338889 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 54.012346 Tz (determine ) Tj 3.091667 0 Td 48.37963 Tz (drug-likeness. ) Tj 4.219444 0 Td 64.814815 Tz (The ) Tj 1.341667 0 Td 59.143519 Tz (most ) Tj 1.575 0 Td 70.216049 Tz (common ) Tj 2.741667 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.907407 Tz (these ) Tj 1.691667 0 Td 72.376543 Tz (met ) Tj 51.428571 0 0 51.428571 0 377.503759 Tm 6.358333 0 Td 43.75 Tz (rics ) Tj 1.225 0 Td 50.771605 Tz (are ) Tj 1.108333 0 Td 48.611111 Tz (Lipinskis ) Tj 3.15 0 Td 42.669753 Tz (rules. ) Tj 1.730556 0 Td 58.333333 Tz (These ) Tj 1.983333 0 Td 45.37037 Tz (rules ) Tj 1.536111 0 Td 50.771605 Tz (are ) Tj 1.069444 0 Td 56.388889 Tz (based ) Tj 1.866667 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 59.62963 Tz (obser ) Tj 51.428571 0 0 51.428571 0 338.371362 Tm 6.358333 0 Td 49.691358 Tz (vation ) Tj 1.905556 0 Td 46.180556 Tz (that ) Tj 1.186111 0 Td 57.523148 Tz (poor ) Tj 1.458333 0 Td 48.611111 Tz (biological ) Tj 3.052778 0 Td 46.180556 Tz (distribution ) Tj 3.422222 0 Td 52.391975 Tz (occurs ) Tj 2.022222 0 Td 64.814815 Tz (when ) Tj 1.691667 0 Td 45.694444 Tz (solubility ) Tj 51.428571 0 0 51.428571 0 294.928205 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.380556 0 Td 50.771605 Tz (permeability ) Tj 4.005556 0 Td 49.691358 Tz (are ) Tj 1.225 0 Td 54.62963 Tz (reduced ) Tj 2.625 0 Td 58.333333 Tz (due ) Tj 1.361111 0 Td 45.37037 Tz (to ) Tj 0.875 0 Td 51.131687 Tz (excessive ) Tj 3.111111 0 Td 54.012346 Tz (molecular ) Tj 51.428571 0 0 51.428571 0 254.17207 Tm 6.338889 0 Td 56.17284 Tz (weight ) Tj 2.275 0 Td 50.462963 Tz (\(>500\), ) Tj 2.391667 0 Td 47.314815 Tz (large ) Tj 1.711111 0 Td 58.796296 Tz (numbers ) Tj 2.722222 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 57.118056 Tz (hydrogen ) Tj 2.994444 0 Td 61.574074 Tz (bond ) Tj 1.711111 0 Td 55.092593 Tz (donors ) Tj 2.236111 0 Td 53.472222 Tz (or ) Tj 51.428571 0 0 51.428571 0 213.732697 Tm 6.358333 0 Td 50.771605 Tz (acceptors ) Tj 2.877778 0 Td 55.092593 Tz (\(>5 ) Tj 1.147222 0 Td 51.851852 Tz (or ) Tj 0.738889 0 Td 58.333333 Tz (a ) Tj 0.427778 0 Td 46.450617 Tz (10, ) Tj 0.972222 0 Td 46.527778 Tz (respectively\), ) Tj 4.025 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 48.935185 Tz (calculated ) Tj 3.033333 0 Td 52.932099 Tz (log ) Tj 1.127778 0 Td 62.87037 Tz (P\(5\). ) Tj 51.428571 0 0 51.428571 0 170.865069 Tm 6.377778 0 Td 50.462963 Tz (Several ) Tj 2.352778 0 Td 51.203704 Tz (extensions ) Tj 3.325 0 Td 45.37037 Tz (to ) Tj 0.836111 0 Td 48.287037 Tz (Lipinski's ) Tj 3.188889 0 Td 45.37037 Tz (rules ) Tj 1.613889 0 Td 55.902778 Tz (have ) Tj 1.575 0 Td 54.6875 Tz (appeared ) Tj 2.858333 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 30 0 0 30 0 2755 Tm 41.833333 0 Td 72.222222 Tz (5 ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.672973 0 Td 74.099099 Tz (10 ) Tj 51.428571 0 0 51.428571 0 2916.145119 Tm 25.297222 0 Td 41.835017 Tz (literature. ) Tj 3.188889 0 Td 34.027778 Tz (It ) Tj 0.719444 0 Td 54.012346 Tz (has ) Tj 1.302778 0 Td 57.523148 Tz (been ) Tj 1.711111 0 Td 57.685185 Tz (found ) Tj 2.041667 0 Td 45.37037 Tz (that ) Tj 1.419444 0 Td 49.907407 Tz (increasing ) Tj 3.325 0 Td 42.424242 Tz (flexibility ) Tj 3.15 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 2871.485437 Tm 25.297222 0 Td 46.450617 Tz (reflected ) Tj 2.702778 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 56.712963 Tz (an ) Tj 0.894444 0 Td 49.583333 Tz (increasing ) Tj 3.188889 0 Td 61.033951 Tz (number ) Tj 2.352778 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 46.450617 Tz (rotatable ) Tj 2.683333 0 Td 57.037037 Tz (bonds ) Tj 1.925 0 Td 52.314815 Tz (reduces ) Tj 51.428571 0 0 51.428571 0 2829.856967 Tm 25.297222 0 Td 46.990741 Tz (oral ) Tj 1.361111 0 Td 44.357639 Tz (bioavailability. ) Tj 4.569444 0 Td 58.333333 Tz (Nine ) Tj 1.613889 0 Td 61.934156 Tz (compounds ) Tj 3.616667 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 46.018519 Tz (identified ) Tj 2.975 0 Td 46.990741 Tz (in ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 2789.600945 Tm 25.297222 0 Td 49.537037 Tz (current ) Tj 2.197222 0 Td 51.851852 Tz (study ) Tj 1.691667 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 53.06713 Tz (reducing ) Tj 2.683333 0 Td 48.611111 Tz (the ) Tj 0.972222 0 Td 56.339031 Tz (ATX-catalyzed ) Tj 4.569444 0 Td 56.712963 Tz (FS-3 ) Tj 1.516667 0 Td 50.555556 Tz (hydrolysis ) Tj 51.428571 0 0 51.428571 0 2745.04401 Tm 25.277778 0 Td 61.574074 Tz (by ) Tj 0.894444 0 Td 72.376543 Tz (50% ) Tj 1.419444 0 Td 53.472222 Tz (or ) Tj 0.758333 0 Td 62.384259 Tz (more ) Tj 1.575 0 Td 45.37037 Tz (at ) Tj 0.758333 0 Td 53.472222 Tz (10 ) Tj 0.816667 0 Td 62.654321 Tz (uM. ) Tj 1.225 0 Td 71.296296 Tz (Two ) Tj 1.4 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.259259 Tz (these ) Tj 1.613889 0 Td 61.574074 Tz (compounds ) Tj 3.480556 0 Td 51.851852 Tz (\(571 ) Tj 1.341667 0 Td 57.523148 Tz (1925 ) Tj 51.428571 0 0 51.428571 0 2704.885714 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 56.712963 Tz (7921385, ) Tj 2.838889 0 Td 52.211934 Tz (presented ) Tj 2.955556 0 Td 55.092593 Tz (above\) ) Tj 2.119444 0 Td 59.953704 Tz (comply ) Tj 2.352778 0 Td 51.851852 Tz (with ) Tj 1.419444 0 Td 39.969136 Tz (all ) Tj 0.855556 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.259259 Tz (Lipinski's ) Tj 48.571429 0 0 48.571429 0 2662 Tm 26.785294 0 Td 49.411765 Tz (rules ) Tj 1.647059 0 Td 62.908497 Tz (and ) Tj 1.255882 0 Td 60.906863 Tz (have ) Tj 1.647059 0 Td 57.647059 Tz (fewer ) Tj 1.894118 0 Td 53.186275 Tz (than ) Tj 1.523529 0 Td 60.04902 Tz (10 ) Tj 0.885294 0 Td 49.945534 Tz (rotatable ) Tj 2.841176 0 Td 56.045752 Tz (bonds, ) Tj 2.223529 0 Td 51.470588 Tz (thus ) Tj 1.4 0 Td 51.470588 Tz (also ) Tj 1.441176 0 Td 72.058824 Tz (meet ) Tj 51.428571 0 0 51.428571 0 2620.005222 Tm 25.297222 0 Td 51.851852 Tz (ing ) Tj 1.302778 0 Td 48.611111 Tz (the ) Tj 1.205556 0 Td 55.497685 Tz (extended ) Tj 2.994444 0 Td 42.424242 Tz (flexibility ) Tj 3.227778 0 Td 47.222222 Tz (metric. ) Tj 2.391667 0 Td 51.041667 Tz (Five ) Tj 1.575 0 Td 48.287037 Tz (additional ) Tj 3.247222 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 2577.19337 Tm 25.277778 0 Td 58.333333 Tz (pounds ) Tj 2.780556 0 Td 55.092593 Tz (\(7839888, ) Tj 3.655556 0 Td 56.30787 Tz (5186522, ) Tj 3.402778 0 Td 56.30787 Tz (5761473, ) Tj 3.402778 0 Td 60.185185 Tz (5538444 ) Tj 3.188889 0 Td 59.41358 Tz (and ) Tj 51.428571 0 0 51.428571 0 2537.002442 Tm 25.297222 0 Td 56.712963 Tz (7905958, ) Tj 2.936111 0 Td 54.552469 Tz (above\) ) Tj 2.119444 0 Td 56.712963 Tz (exceed ) Tj 2.216667 0 Td 54.282407 Tz (only ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 54.012346 Tz (molecular ) Tj 3.111111 0 Td 54.012346 Tz (weight ) Tj 2.158333 0 Td 46.666667 Tz (limit ) Tj 1.555556 0 Td 61.574074 Tz (by ) Tj 51.428571 0 0 51.428571 0 2494.151515 Tm 25.297222 0 Td 58.333333 Tz (amounts ) Tj 2.722222 0 Td 52.777778 Tz (ranging ) Tj 2.45 0 Td 57.523148 Tz (from ) Tj 1.652778 0 Td 55.092593 Tz (7 ) Tj 0.583333 0 Td 55.812757 Tz (\(7905958\) ) Tj 3.266667 0 Td 45.37037 Tz (to ) Tj 0.855556 0 Td 58.333333 Tz (148 ) Tj 1.263889 0 Td 53.472222 Tz (\(5186522\). ) Tj 3.461111 0 Td 66.975309 Tz (One ) Tj 51.428571 0 0 51.428571 0 2454.656899 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 56.532922 Tz (\(5564949\) ) Tj 3.208333 0 Td 55.555556 Tz (exceeds ) Tj 2.488889 0 Td 54.282407 Tz (only ) Tj 1.536111 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 49.259259 Tz (calculated ) Tj 3.169444 0 Td 50.771605 Tz (log ) Tj 1.147222 0 Td 64.814815 Tz (P ) Tj 0.544444 0 Td 57.253086 Tz (cri ) Tj 51.428571 0 0 51.428571 0 2411.531707 Tm 25.277778 0 Td 44.444444 Tz (terion. ) Tj 2.1 0 Td 62.654321 Tz (The ) Tj 1.322222 0 Td 43.425926 Tz (final ) Tj 1.516667 0 Td 63.599537 Tz (compound ) Tj 3.266667 0 Td 56.532922 Tz (\(5210574\) ) Tj 3.247222 0 Td 54.166667 Tz (exceeds ) Tj 2.508333 0 Td 58.333333 Tz (two ) Tj 1.283333 0 Td 41.049383 Tz (criteria, ) Tj 51.428571 0 0 51.428571 0 2370.622739 Tm 25.297222 0 Td 49.259259 Tz (calculated ) Tj 3.247222 0 Td 50.771605 Tz (log ) Tj 1.225 0 Td 64.814815 Tz (P ) Tj 0.641667 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 54.012346 Tz (molecular ) Tj 3.169444 0 Td 50.925926 Tz (weight. ) Tj 2.469444 0 Td 64.814815 Tz (None ) Tj 1.808333 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 2328.032569 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.294444 0 Td 48.206019 Tz (violated ) Tj 2.508333 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 61.868687 Tz (recommended ) Tj 4.258333 0 Td 45.37037 Tz (limits ) Tj 1.808333 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 46.450617 Tz (rotatable ) Tj 2.663889 0 Td 52.932099 Tz (bonds, ) Tj 51.428571 0 0 51.428571 0 2289.103774 Tm 25.277778 0 Td 57.118056 Tz (hydrogen ) Tj 2.877778 0 Td 61.574074 Tz (bond ) Tj 1.575 0 Td 49.259259 Tz (acceptors, ) Tj 3.091667 0 Td 51.851852 Tz (or ) Tj 0.719444 0 Td 57.523148 Tz (hydrogen ) Tj 2.877778 0 Td 60.763889 Tz (bond ) Tj 1.594444 0 Td 50.925926 Tz (donors. ) Tj 2.275 0 Td 59.953704 Tz (Thus ) Tj 1.575 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2249.336774 Tm 25.297222 0 Td 51.851852 Tz (goal ) Tj 1.497222 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 53.347578 Tz (demonstrating ) Tj 4.394444 0 Td 46.180556 Tz (that ) Tj 1.302778 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 37.268519 Tz (is ) Tj 0.7 0 Td 58.333333 Tz (a ) Tj 0.797222 0 Td 55.092593 Tz (druggable ) Tj 3.344444 0 Td 46.450617 Tz (target ) Tj 1.886111 0 Td 55.092593 Tz (has ) Tj 51.428571 0 0 51.428571 0 2203.895288 Tm 25.277778 0 Td 57.523148 Tz (been ) Tj 1.672222 0 Td 53.472222 Tz (achieved ) Tj 2.877778 0 Td 43.75 Tz (in ) Tj 0.836111 0 Td 53.148148 Tz (terms ) Tj 1.905556 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 49.907407 Tz (these ) Tj 1.827778 0 Td 50.231481 Tz (nine ) Tj 1.497222 0 Td 58.657407 Tz (compounds, ) Tj 3.830556 0 Td 43.75 Tz (at ) Tj 0.816667 0 Td 44.722222 Tz (least ) Tj 51.428571 0 0 51.428571 0 2164.87309 Tm 25.297222 0 Td 50.05144 Tz (exhibited ) Tj 2.8 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 51.131687 Tz (necessary ) Tj 2.916667 0 Td 44.444444 Tz (results ) Tj 2.002778 0 Td 56.388889 Tz (under ) Tj 1.788889 0 Td 48.611111 Tz (Lipinskis ) Tj 3.091667 0 Td 45.37037 Tz (rules ) Tj 1.477778 0 Td 55.555556 Tz (coupled ) Tj 51.428571 0 0 51.428571 0 2121.859903 Tm 25.277778 0 Td 54.282407 Tz (with ) Tj 1.477778 0 Td 46.450617 Tz (effective ) Tj 2.625 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 46.990741 Tz (inhibition ) Tj 2.994444 0 Td 46.450617 Tz (\(as ) Tj 1.030556 0 Td 51.49177 Tz (presented ) Tj 2.936111 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 55.092593 Tz (Examples, ) Tj 51.428571 0 0 51.428571 0 2078 Tm 25.277778 0 Td 51.851852 Tz (below\). ) Tj 51.428571 0 0 51.428571 0 2039.830552 Tm 26.016667 0 Td 66.435185 Tz (AS ) Tj 0.991667 0 Td 49.259259 Tz (Such, ) Tj 1.672222 0 Td 50.555556 Tz (these ) Tj 1.672222 0 Td 61.934156 Tz (compounds ) Tj 3.558333 0 Td 66.975309 Tz (may ) Tj 1.380556 0 Td 58.333333 Tz (be ) Tj 0.855556 0 Td 52.256944 Tz (included ) Tj 2.683333 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 58.333333 Tz (a ) Tj 0.525 0 Td 64.351852 Tz (composi ) Tj 51.428571 0 0 51.428571 0 1999.575448 Tm 25.277778 0 Td 46.990741 Tz (tion ) Tj 1.361111 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 57.253086 Tz (any ) Tj 1.205556 0 Td 53.472222 Tz (type ) Tj 1.477778 0 Td 46.180556 Tz (that ) Tj 1.302778 0 Td 37.268519 Tz (is ) Tj 0.622222 0 Td 51.446759 Tz (properly ) Tj 2.683333 0 Td 49.259259 Tz (ingestable ) Tj 3.130556 0 Td 59.953704 Tz (by ) Tj 0.933333 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 44.560185 Tz (patient. ) Tj 2.391667 0 Td 35.648148 Tz (It ) Tj 0.602778 0 Td 40.509259 Tz (is ) Tj 51.428571 0 0 51.428571 0 1958.940594 Tm 25.297222 0 Td 49.259259 Tz (preferable ) Tj 3.227778 0 Td 44.560185 Tz (that ) Tj 1.322222 0 Td 55.092593 Tz (such ) Tj 1.575 0 Td 54.012346 Tz (compositions ) Tj 4.122222 0 Td 59.953704 Tz (be ) Tj 0.952778 0 Td 47.530864 Tz (orally ) Tj 1.983333 0 Td 47.138047 Tz (ingestable, ) Tj 3.363889 0 Td 51.851852 Tz (but ) Tj 51.428571 0 0 51.428571 0 1913.599749 Tm 25.277778 0 Td 51.851852 Tz (they ) Tj 1.477778 0 Td 66.975309 Tz (may ) Tj 1.4 0 Td 56.712963 Tz (be ) Tj 0.855556 0 Td 53.877315 Tz (provided ) Tj 2.780556 0 Td 48.611111 Tz (for ) Tj 1.011111 0 Td 50.968013 Tz (intravenous ) Tj 3.577778 0 Td 48.881173 Tz (introduction ) Tj 3.694444 0 Td 51.851852 Tz (as ) Tj 0.816667 0 Td 46.666667 Tz (well. ) Tj 51.428571 0 0 51.428571 0 1873.515994 Tm 26.036111 0 Td 48.611111 Tz (In ) Tj 0.894444 0 Td 53.796296 Tz (terms ) Tj 1.925 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 57.523148 Tz (form ) Tj 1.730556 0 Td 54.282407 Tz (Such ) Tj 1.613889 0 Td 53.742284 Tz (compositions ) Tj 4.2 0 Td 68.055556 Tz (may ) Tj 1.536111 0 Td 46.018519 Tz (take, ) Tj 1.672222 0 Td 58.333333 Tz (any ) Tj 51.428571 0 0 51.428571 0 1831.588875 Tm 25.297222 0 Td 46.990741 Tz (orally ) Tj 1.866667 0 Td 49.259259 Tz (ingestable ) Tj 3.111111 0 Td 58.333333 Tz (form ) Tj 1.594444 0 Td 38.888889 Tz (is ) Tj 0.622222 0 Td 47.530864 Tz (possible. ) Tj 2.722222 0 Td 54.282407 Tz (This ) Tj 1.516667 0 Td 36.458333 Tz (list ) Tj 1.030556 0 Td 48.251029 Tz (includes, ) Tj 2.8 0 Td 52.777778 Tz (without ) Tj 51.428571 0 0 51.428571 0 1790.34 Tm 25.297222 0 Td 45.37037 Tz (limitation, ) Tj 3.325 0 Td 44.965278 Tz (liquids, ) Tj 2.488889 0 Td 46.990741 Tz (liquid ) Tj 2.002778 0 Td 48.971193 Tz (capsules, ) Tj 2.936111 0 Td 43.75 Tz (tablets, ) Tj 2.430556 0 Td 52.391975 Tz (coated ) Tj 2.177778 0 Td 43.344907 Tz (tablets, ) Tj 51.428571 0 0 51.428571 0 1746.218863 Tm 25.297222 0 Td 46.990741 Tz (minitablets, ) Tj 3.558333 0 Td 51.041667 Tz (capsules ) Tj 2.625 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 47.962963 Tz (individual ) Tj 3.052778 0 Td 50.771605 Tz (beads, ) Tj 1.944444 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 40.185185 Tz (like. ) Tj 1.419444 0 Td 42.12963 Tz (If ) Tj 0.583333 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 1705.613267 Tm 25.297222 0 Td 52.932099 Tz (coated ) Tj 2.138889 0 Td 44.830247 Tz (tablet ) Tj 1.866667 0 Td 52.5 Tz (form, ) Tj 1.827778 0 Td 54.282407 Tz (such ) Tj 1.575 0 Td 53.472222 Tz (compositions ) Tj 4.122222 0 Td 68.055556 Tz (may ) Tj 1.458333 0 Td 58.333333 Tz (be ) Tj 0.952778 0 Td 55.092593 Tz (of ) Tj 0.836111 0 Td 50.05144 Tz (Sustained ) Tj 51.428571 0 0 51.428571 0 1664.741259 Tm 25.297222 0 Td 48.148148 Tz (release ) Tj 2.138889 0 Td 47.314815 Tz (type, ) Tj 1.536111 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 68.055556 Tz (may ) Tj 1.341667 0 Td 53.472222 Tz (includea ) Tj 2.722222 0 Td 52.083333 Tz (waterinsoluble ) Tj 4.472222 0 Td 51.851852 Tz (but ) Tj 1.011111 0 Td 56.893004 Tz (permeable ) Tj 52.857143 0 0 52.857143 0 1623.874172 Tm 24.613514 0 Td 45.720721 Tz (film ) Tj 1.475676 0 Td 50.45045 Tz (coating ) Tj 2.459459 0 Td 51.883702 Tz (surrounding ) Tj 3.727027 0 Td 53.603604 Tz (a ) Tj 0.681081 0 Td 50.45045 Tz (core ) Tj 1.551351 0 Td 44.66967 Tz (tablet ) Tj 1.891892 0 Td 57.807808 Tz (and ) Tj 1.381081 0 Td 50.45045 Tz (a ) Tj 0.643243 0 Td 43.881381 Tz (particulate, ) Tj 51.428571 0 0 51.428571 0 1581.357055 Tm 25.277778 0 Td 49.074074 Tz (water-soluble, ) Tj 4.433333 0 Td 54.282407 Tz (pore-forming ) Tj 4.258333 0 Td 48.611111 Tz (material ) Tj 2.683333 0 Td 50.771605 Tz (dispersed ) Tj 3.052778 0 Td 50.771605 Tz (within ) Tj 2.158333 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 1540.527578 Tm 25.297222 0 Td 47.800926 Tz (film ) Tj 1.283333 0 Td 48.206019 Tz (coating. ) Tj 2.469444 0 Td 59.143519 Tz (Such ) Tj 1.555556 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 55.092593 Tz (system ) Tj 2.138889 0 Td 50.231481 Tz (thus ) Tj 1.341667 0 Td 51.446759 Tz (provides ) Tj 2.605556 0 Td 56.712963 Tz (an ) Tj 0.836111 0 Td 54.166667 Tz (osmotic ) Tj 2.391667 0 Td 50.231481 Tz (gradient ) Tj 51.428571 0 0 51.428571 0 1498.46356 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 53.703704 Tz (channel ) Tj 2.430556 0 Td 55.555556 Tz (forming ) Tj 2.508333 0 Td 51.851852 Tz (system. ) Tj 2.352778 0 Td 51.388889 Tz (Typical ) Tj 2.352778 0 Td 50.231481 Tz (coatings ) Tj 2.566667 0 Td 56.712963 Tz (have ) Tj 1.516667 0 Td 52.662037 Tz (included ) Tj 51.428571 0 0 51.428571 0 1458.270809 Tm 25.297222 0 Td 54.6875 Tz (carnauba ) Tj 2.780556 0 Td 57.523148 Tz (wax, ) Tj 1.555556 0 Td 49.016204 Tz (cysteine ) Tj 2.527778 0 Td 50.694444 Tz (hydrochloride, ) Tj 4.413889 0 Td 55.34188 Tz (hydroxypropyl ) Tj 4.530556 0 Td 68.865741 Tz (meth ) Tj 51.428571 0 0 51.428571 0 1416.522459 Tm 25.277778 0 Td 46.450617 Tz (ylcellulose, ) Tj 3.597222 0 Td 61.213992 Tz (magnesium ) Tj 3.577778 0 Td 43.930041 Tz (Stearate, ) Tj 2.625 0 Td 49.016204 Tz (microcrystalline ) Tj 4.938889 0 Td 45.37037 Tz (cellulose, ) Tj 51.428571 0 0 51.428571 0 1374.320958 Tm 25.297222 0 Td 52.121914 Tz (polyethylene ) Tj 3.927778 0 Td 50.231481 Tz (glycol ) Tj 2.022222 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 49.826389 Tz (titanium ) Tj 2.625 0 Td 48.206019 Tz (dioxide. ) Tj 2.547222 0 Td 56.388889 Tz (Other ) Tj 1.866667 0 Td 48.611111 Tz (therapeutic ) Tj 51.428571 0 0 51.428571 0 1330.474328 Tm 25.297222 0 Td 51.311728 Tz (agents ) Tj 2.041667 0 Td 68.055556 Tz (may ) Tj 1.4 0 Td 58.333333 Tz (be ) Tj 0.875 0 Td 51.851852 Tz (included ) Tj 2.644444 0 Td 53.472222 Tz (with ) Tj 1.458333 0 Td 49.907407 Tz (these ) Tj 1.652778 0 Td 50.555556 Tz (anticancer ) Tj 3.169444 0 Td 51.311728 Tz (agents ) Tj 2.022222 0 Td 48.611111 Tz (as ) Tj 0.777778 0 Td 46.666667 Tz (well, ) Tj 51.428571 0 0 51.428571 0 1287.634615 Tm 25.297222 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 53.472222 Tz (long ) Tj 1.419444 0 Td 48.611111 Tz (as ) Tj 0.758333 0 Td 48.148148 Tz (neither ) Tj 2.119444 0 Td 45.37037 Tz (interferes ) Tj 2.897222 0 Td 51.851852 Tz (with ) Tj 1.419444 0 Td 47.530864 Tz (the ) Tj 0.991667 0 Td 47.863248 Tz (effectiveness ) Tj 3.85 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 48.611111 Tz (the ) Tj 0.972222 0 Td 51.851852 Tz (other ) Tj 51.428571 0 0 51.428571 0 1247.655738 Tm 25.297222 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 47.530864 Tz (user's ) Tj 1.905556 0 Td 52.5 Tz (body. ) Tj 38.571429 0 0 38.571429 0 1174 Tm 37.151852 0 Td 101.783265 Tz (PREFERRED ) Tj 5.755556 0 Td 107.239057 Tz (EMBODIMENTS ) Tj 7.337037 0 Td 101.54321 Tz (OF ) Tj 1.451852 0 Td 105.144033 Tz (THE ) Tj 38.571429 0 0 38.571429 0 1132 Tm 42.725926 0 Td 98.902606 Tz (INVENTION ) Tj 51.428571 0 0 51.428571 0 1045.533686 Tm 26.016667 0 Td 63.734568 Tz (The ) Tj 1.380556 0 Td 46.180556 Tz (specific ) Tj 2.469444 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 52.932099 Tz (below, ) Tj 2.158333 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 51.041667 Tz (well ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 51.49177 Tz (following ) Tj 51.428571 0 0 51.428571 0 1003.858491 Tm 25.297222 0 Td 51.851852 Tz (exemplified ) Tj 3.558333 0 Td 57.87037 Tz (methods ) Tj 2.586111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 54.73251 Tz (producing ) Tj 3.072222 0 Td 55.092593 Tz (Such ) Tj 1.458333 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 57.87037 Tz (methods ) Tj 2.566667 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 52.5 Tz (using ) Tj 51.428571 0 0 51.428571 0 961.782205 Tm 25.316667 0 Td 54.282407 Tz (Such ) Tj 1.672222 0 Td 61.574074 Tz (compounds ) Tj 3.675 0 Td 49.691358 Tz (are ) Tj 1.263889 0 Td 49.96142 Tz (non-limiting ) Tj 3.966667 0 Td 43.75 Tz (in ) Tj 0.894444 0 Td 50.231481 Tz (nature ) Tj 2.119444 0 Td 59.41358 Tz (and ) Tj 1.419444 0 Td 49.691358 Tz (are ) Tj 1.205556 0 Td 51.041667 Tz (thus ) Tj 51.428571 0 0 51.428571 0 918.36803 Tm 25.297222 0 Td 47.314815 Tz (indicative ) Tj 2.994444 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 49.691358 Tz (preferred ) Tj 2.838889 0 Td 59.511785 Tz (embodiments ) Tj 4.122222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 43.75 Tz (this ) Tj 1.244444 0 Td 47.962963 Tz (invention. ) Tj 51.428571 0 0 51.428571 0 878.217712 Tm 26.016667 0 Td 63.734568 Tz (The ) Tj 1.244444 0 Td 47.395833 Tz (efficacy ) Tj 2.411111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 49.907407 Tz (these ) Tj 1.594444 0 Td 62.294239 Tz (compounds ) Tj 3.5 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 54.768519 Tz (determined ) Tj 3.402778 0 Td 59.953704 Tz (by ) Tj 0.855556 0 Td 58.981481 Tz (evalu ) Tj 51.428571 0 0 51.428571 0 836.671498 Tm 25.297222 0 Td 47.962963 Tz (ating ) Tj 1.672222 0 Td 50.501543 Tz (fluorescence ) Tj 3.811111 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 50.411523 Tz (autotaxin ) Tj 2.936111 0 Td 43.75 Tz (at ) Tj 0.719444 0 Td 46.180556 Tz (specific ) Tj 2.45 0 Td 51.851852 Tz (wavelengths. ) Tj 3.947222 0 Td 63.734568 Tz (The ) Tj 51.428571 0 0 51.428571 0 794.618182 Tm 25.277778 0 Td 43.75 Tz (test ) Tj 1.186111 0 Td 51.041667 Tz (protocol ) Tj 2.644444 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 48.611111 Tz (as ) Tj 0.797222 0 Td 47.800926 Tz (follows: ) Tj 51.428571 0 0 51.428571 0 751.181929 Tm 26.036111 0 Td 55.555556 Tz (Interms ) Tj 2.469444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 75.617284 Tz (ATX ) Tj 1.516667 0 Td 46.666667 Tz (inhibition ) Tj 2.936111 0 Td 49.016204 Tz (analysis ) Tj 2.508333 0 Td 49.907407 Tz (determinations, ) Tj 4.627778 0 Td 105.864198 Tz (MDA ) Tj 52.857143 0 0 52.857143 0 708 Tm 24.613514 0 Td 66.216216 Tz (MB-435 ) Tj 2.610811 0 Td 43.513514 Tz (cells ) Tj 1.494595 0 Td 58.333333 Tz (were ) Tj 1.608108 0 Td 48.085586 Tz (cultured ) Tj 2.516216 0 Td 45.720721 Tz (at ) Tj 0.737838 0 Td 55.705706 Tz (37 ) Tj 1.22973 0 Td 53.603604 Tz (C. ) Tj 0.851351 0 Td 57.807808 Tz (and ) Tj 1.267568 0 Td 75.675676 Tz (5% ) Tj 1.116216 0 Td 69.369369 Tz (CO, ) Tj 1.494595 0 Td 45.720721 Tz (in ) Tj 0.794595 0 Td 70.42042 Tz (Dul ) Tj 51.428571 0 0 51.428571 0 667.851711 Tm 25.277778 0 Td 53.240741 Tz (becco's ) Tj 2.644444 0 Td 55.497685 Tz (Modified ) Tj 3.111111 0 Td 54.444444 Tz (Eagle ) Tj 2.022222 0 Td 67.515432 Tz (Medium ) Tj 2.877778 0 Td 76.157407 Tz (\(DMEM\) ) Tj 3.169444 0 Td 55.092593 Tz (\(MediaTech, ) Tj 51.428571 0 0 51.428571 0 629.004926 Tm 25.316667 0 Td 56.30787 Tz (Herndon, ) Tj 2.916667 0 Td 49.421296 Tz (Va.\) ) Tj 1.4 0 Td 51.527778 Tz (containing ) Tj 3.325 0 Td 77.777778 Tz (5% ) Tj 1.186111 0 Td 42.777778 Tz (fetal ) Tj 1.516667 0 Td 55.092593 Tz (bovine ) Tj 2.216667 0 Td 58.981481 Tz (serum ) Tj 2.022222 0 Td 52.572016 Tz (\(Hyclone, ) Tj 51.428571 0 0 51.428571 0 589.212579 Tm 25.316667 0 Td 55.632716 Tz (Logan, ) Tj 2.255556 0 Td 50.231481 Tz (Utah\), ) Tj 2.080556 0 Td 58.333333 Tz (100 ) Tj 1.263889 0 Td 61.574074 Tz (U/ml ) Tj 1.691667 0 Td 43.897306 Tz (penicillin, ) Tj 3.208333 0 Td 58.333333 Tz (100 ) Tj 1.536111 0 Td 57.523148 Tz (g/ml ) Tj 1.633333 0 Td 52.662037 Tz (streptomycin ) Tj 51.428571 0 0 51.428571 0 547.981795 Tm 25.316667 0 Td 52.932099 Tz (\(Hyclone, ) Tj 3.208333 0 Td 55.092593 Tz (Logan, ) Tj 2.294444 0 Td 54.444444 Tz (Utah\) ) Tj 1.944444 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 60.493827 Tz (292 ) Tj 1.691667 0 Td 58.333333 Tz (g/ml ) Tj 1.730556 0 Td 54.208754 Tz (L-glutamine ) Tj 3.869444 0 Td 75.617284 Tz (\(Hy ) Tj 51.428571 0 0 51.428571 0 502.887425 Tm 25.297222 0 Td 48.611111 Tz (clone, ) Tj 1.925 0 Td 55.092593 Tz (Logan, ) Tj 2.138889 0 Td 49.691358 Tz (Utah\). ) Tj 1.925 0 Td 49.907407 Tz (Cells ) Tj 1.652778 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 61.574074 Tz (grown ) Tj 1.983333 0 Td 45.37037 Tz (to ) Tj 0.680556 0 Td 71.296296 Tz (~80% ) Tj 1.866667 0 Td 52.5 Tz (confluence ) Tj 3.247222 0 Td 46.990741 Tz (at ) Tj 51.428571 0 0 51.428571 0 460.441696 Tm 25.277778 0 Td 59.62963 Tz (which ) Tj 1.886111 0 Td 55.092593 Tz (time ) Tj 1.419444 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 43.425926 Tz (cells ) Tj 1.458333 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 60.493827 Tz (washed ) Tj 2.294444 0 Td 52.5 Tz (twice ) Tj 1.691667 0 Td 52.662037 Tz (with ) Tj 1.380556 0 Td 42.592593 Tz (sterile ) Tj 1.886111 0 Td 55.092593 Tz (phosphate ) Tj 51.428571 0 0 51.428571 0 418.752577 Tm 25.277778 0 Td 51.041667 Tz (buffered ) Tj 2.722222 0 Td 46.990741 Tz (saline ) Tj 1.944444 0 Td 47.314815 Tz (prior ) Tj 1.691667 0 Td 43.75 Tz (to ) Tj 0.816667 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 49.421296 Tz (addition ) Tj 2.644444 0 Td 56.712963 Tz (of ) Tj 0.855556 0 Td 57.685185 Tz (serum ) Tj 2.041667 0 Td 46.180556 Tz (free ) Tj 1.419444 0 Td 93.171296 Tz (DMEM ) Tj 51.428571 0 0 51.428571 0 379.292453 Tm 25.297222 0 Td 51.203704 Tz (containing ) Tj 3.286111 0 Td 51.58179 Tz (L-glutamine. ) Tj 3.908333 0 Td 54.79798 Tz (Conditioned ) Tj 3.811111 0 Td 64.814815 Tz (medium ) Tj 2.527778 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 48.971193 Tz (collected ) Tj 51.428571 0 0 51.428571 0 339.252163 Tm 25.297222 0 Td 44.722222 Tz (after ) Tj 1.594444 0 Td 56.388889 Tz (24-30 ) Tj 1.925 0 Td 49.151235 Tz (hours, ) Tj 2.041667 0 Td 56.17284 Tz (supplemented ) Tj 4.297222 0 Td 52.662037 Tz (with ) Tj 1.516667 0 Td 72.376543 Tz (20% ) Tj 1.555556 0 Td 51.851852 Tz (ethylene ) Tj 2.702778 0 Td 50.771605 Tz (glycol ) Tj 51.428571 0 0 51.428571 0 296.486683 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 43.930041 Tz (clarified ) Tj 2.508333 0 Td 59.953704 Tz (by ) Tj 0.855556 0 Td 48.37963 Tz (centrifugation ) Tj 4.2 0 Td 43.75 Tz (at ) Tj 0.661111 0 Td 61.574074 Tz (3000xg ) Tj 2.352778 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 59.143519 Tz (4C. ) Tj 1.575 0 Td 49.691358 Tz (for ) Tj 1.069444 0 Td 53.472222 Tz (10 ) Tj 40 0 0 40 0 259 Tm 32.575 0 Td 66.666667 Tz (min. ) Tj 2.125 0 Td 83.333333 Tz (The ) Tj 2.075 0 Td 74.166667 Tz (media ) Tj 2.75 0 Td 80.555556 Tz (was ) Tj 2 0 Td 66.319444 Tz (concentrated ) Tj 5.375 0 Td 77.777778 Tz (~10 ) Tj 1.9 0 Td 63.541667 Tz (fold ) Tj 2.05 0 Td 75 Tz (and ) Tj 1.85 0 Td 64.583333 Tz (buffer ) Tj 51.428571 0 0 51.428571 0 214.432432 Tm 25.297222 0 Td 57.613169 Tz (exchanged ) Tj 3.266667 0 Td 46.990741 Tz (into ) Tj 1.283333 0 Td 48.611111 Tz (Tris ) Tj 1.361111 0 Td 52.932099 Tz (\(50 ) Tj 1.147222 0 Td 76.697531 Tz (mM, ) Tj 1.555556 0 Td 74.537037 Tz (pH ) Tj 1.088889 0 Td 46.990741 Tz (7.4\) ) Tj 1.302778 0 Td 51.203704 Tz (containing ) Tj 3.266667 0 Td 72.376543 Tz (20% ) Tj 1.497222 0 Td 56.388889 Tz (ethyl ) Tj 51.428571 0 0 51.428571 0 169.661836 Tm 25.297222 0 Td 56.17284 Tz (ene ) Tj 1.127778 0 Td 49.691358 Tz (glycol ) Tj 1.963889 0 Td 51.851852 Tz (using ) Tj 1.672222 0 Td 56.712963 Tz (an ) Tj 0.758333 0 Td 64.274691 Tz (Amicon ) Tj 2.469444 0 Td 60.763889 Tz (8050 ) Tj 1.575 0 Td 42.939815 Tz (cell ) Tj 1.166667 0 Td 41.589506 Tz (fitted ) Tj 1.633333 0 Td 51.851852 Tz (with ) Tj 1.361111 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 73.726852 Tz (PM30 ) Tj 1.866667 0 Td 39.429012 Tz (filter ) Tj ET Q endstream endobj 128 0 obj << /Length 1 >> stream q endstream endobj 129 0 obj << /Length 23592 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,969,590 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 14.661111 0 Td 71.296296 Tz (11 ) Tj 51.428571 0 0 51.428571 0 2915.795181 Tm 6.377778 0 Td 47.727273 Tz (\(Millipore, ) Tj 3.422222 0 Td 44.074074 Tz (Billerica, ) Tj 2.877778 0 Td 50.462963 Tz (Mass.\). ) Tj 2.333333 0 Td 51.851852 Tz (Aliquots ) Tj 2.722222 0 Td 61.574074 Tz (of ) Tj 0.855556 0 Td 51.311728 Tz (concentrated ) Tj 3.927778 0 Td 72.376543 Tz (con ) Tj 40 0 0 40 0 2878 Tm 8.175 0 Td 64.0625 Tz (ditioned ) Tj 3.325 0 Td 75.833333 Tz (media ) Tj 2.5 0 Td 76.041667 Tz (were ) Tj 2.075 0 Td 63.194444 Tz (stored ) Tj 2.5 0 Td 56.25 Tz (at ) Tj 0.875 0 Td 80.208333 Tz (4C. ) Tj 2.2 0 Td 56.666667 Tz (until ) Tj 2 0 Td 66.666667 Tz (needed. ) Tj 51.428571 0 0 51.428571 0 2815.151351 Tm 7.097222 0 Td 77.777778 Tz (ATX ) Tj 1.711111 0 Td 46.990741 Tz (inhibition ) Tj 3.15 0 Td 61.574074 Tz (was ) Tj 1.419444 0 Td 54.62963 Tz (assayed ) Tj 2.605556 0 Td 52.5 Tz (using ) Tj 1.925 0 Td 55.902778 Tz (FS-3 ) Tj 1.711111 0 Td 54.282407 Tz (\(Echelon ) Tj 2.955556 0 Td 69.135802 Tz (Bio ) Tj 51.428571 0 0 51.428571 0 2770.706468 Tm 6.377778 0 Td 47.890947 Tz (sciences, ) Tj 2.780556 0 Td 41.481481 Tz (Inc., ) Tj 1.438889 0 Td 47.800926 Tz (Salt ) Tj 1.361111 0 Td 58.333333 Tz (Lake ) Tj 1.575 0 Td 46.018519 Tz (City, ) Tj 1.575 0 Td 52.5 Tz (Utah, ) Tj 1.769444 0 Td 70.486111 Tz (USA\) ) Tj 1.866667 0 Td 48.611111 Tz (as ) Tj 0.758333 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 48.251029 Tz (substrate ) Tj 2.741667 0 Td 60.493827 Tz (and ) Tj 40 0 0 40 0 2734 Tm 8.175 0 Td 81.944444 Tz (~10 ) Tj 1.975 0 Td 67.5 Tz (times ) Tj 2.55 0 Td 66.666667 Tz (concentrated ) Tj 5.3 0 Td 67.424242 Tz (conditioned ) Tj 4.975 0 Td 67.916667 Tz (serum-free ) Tj 4.65 0 Td 83.333333 Tz (medium ) Tj 51.428571 0 0 51.428571 0 2682 Tm 6.377778 0 Td 70 Tz (\(CCM\) ) Tj 2.411111 0 Td 57.523148 Tz (from ) Tj 1.730556 0 Td 93.981481 Tz (MDA ) Tj 2.002778 0 Td 67.515432 Tz (MB-435 ) Tj 2.780556 0 Td 44.074074 Tz (cells ) Tj 1.652778 0 Td 50.231481 Tz (as ) Tj 0.952778 0 Td 49.691358 Tz (the ) Tj 1.225 0 Td 52.391975 Tz (source ) Tj 2.197222 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 65.625 Tz (ATX. ) Tj 51.428571 0 0 51.428571 0 2643.564706 Tm 6.358333 0 Td 57.253086 Tz (Assays ) Tj 2.177778 0 Td 59.143519 Tz (were ) Tj 1.516667 0 Td 56.893004 Tz (performed ) Tj 3.169444 0 Td 46.990741 Tz (in ) Tj 0.680556 0 Td 53.240741 Tz (96-well ) Tj 2.333333 0 Td 47.530864 Tz (plates ) Tj 1.866667 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 89.660494 Tz (CCM ) Tj 1.730556 0 Td 61.574074 Tz (compris ) Tj 51.428571 0 0 51.428571 0 2595.464329 Tm 6.358333 0 Td 51.851852 Tz (ing ) Tj 1.05 0 Td 50.05144 Tz (one-third ) Tj 2.819444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 42.777778 Tz (total ) Tj 1.438889 0 Td 59.953704 Tz (volume ) Tj 2.294444 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 42.777778 Tz (final ) Tj 1.477778 0 Td 55.092593 Tz (FS-3 ) Tj 1.497222 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 56.30787 Tz (charcoal ) Tj 51.428571 0 0 51.428571 0 2552.826618 Tm 6.377778 0 Td 48.611111 Tz (stripped ) Tj 2.469444 0 Td 43.425926 Tz (fatty ) Tj 1.438889 0 Td 51.041667 Tz (acid ) Tj 1.380556 0 Td 46.180556 Tz (free ) Tj 1.283333 0 Td 76.697531 Tz (BSA ) Tj 1.477778 0 Td 50.694444 Tz (concentrations ) Tj 4.394444 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 38.888889 Tz (1 ) Tj 0.427778 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 61.574074 Tz (30 ) Tj 0.913889 0 Td 81.018519 Tz (uM ) Tj 1.108333 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 2509.986996 Tm 6.358333 0 Td 51.851852 Tz (assay ) Tj 1.730556 0 Td 50.231481 Tz (buffer ) Tj 1.963889 0 Td 43.75 Tz (\(1 ) Tj 0.797222 0 Td 97.222222 Tz (mM ) Tj 1.341667 0 Td 55.902778 Tz (each ) Tj 1.516667 0 Td 64.00463 Tz (CaCl ) Tj 1.944444 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 59.953704 Tz (MgCl2, ) Tj 2.352778 0 Td 51.851852 Tz (5 ) Tj 0.544444 0 Td 98.842593 Tz (mM ) Tj 1.380556 0 Td 69.135802 Tz (KCl ) Tj 1.613889 0 Td 58.333333 Tz (140 ) Tj 51.428571 0 0 51.428571 0 2464.468193 Tm 6.358333 0 Td 100.462963 Tz (mM ) Tj 1.419444 0 Td 56.388889 Tz (NaCl, ) Tj 1.905556 0 Td 59.953704 Tz (50 ) Tj 0.913889 0 Td 100.462963 Tz (mM ) Tj 1.380556 0 Td 47.800926 Tz (Tris ) Tj 1.341667 0 Td 74.537037 Tz (pH ) Tj 1.088889 0 Td 44.074074 Tz (8.0\). ) Tj 1.555556 0 Td 53.20216 Tz (Fluorescence ) Tj 3.986111 0 Td 63.734568 Tz (was ) Tj 1.361111 0 Td 51.851852 Tz (read ) Tj 1.419444 0 Td 45.37037 Tz (at ) Tj 0.738889 0 Td 55.092593 Tz (5 ) Tj 51.428571 0 0 51.428571 0 2423.775713 Tm 6.358333 0 Td 56.17284 Tz (minute ) Tj 2.275 0 Td 45.37037 Tz (intervals ) Tj 2.683333 0 Td 59.953704 Tz (by ) Tj 0.952778 0 Td 51.851852 Tz (a ) Tj 0.583333 0 Td 57.118056 Tz (Synergy2 ) Tj 2.975 0 Td 55.092593 Tz (system ) Tj 2.275 0 Td 52.662037 Tz (\(BioTek, ) Tj 2.761111 0 Td 54.372428 Tz (Winooski, ) Tj 51.428571 0 0 51.428571 0 2378.75447 Tm 6.358333 0 Td 47.800926 Tz (Vt.\) ) Tj 1.283333 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 47.314815 Tz (excitation ) Tj 2.955556 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 53.06713 Tz (emission ) Tj 2.722222 0 Td 54.208754 Tz (wavelengths ) Tj 3.675 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 58.333333 Tz (485 ) Tj 1.186111 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 59.41358 Tz (538 ) Tj 51.428571 0 0 51.428571 0 2337.620347 Tm 6.358333 0 Td 61.574074 Tz (nm, ) Tj 1.283333 0 Td 46.118234 Tz (respectively. ) Tj 3.811111 0 Td 50 Tz (Results ) Tj 2.275 0 Td 48.611111 Tz (are ) Tj 1.069444 0 Td 61.574074 Tz (shown ) Tj 2.002778 0 Td 46.990741 Tz (at ) Tj 0.777778 0 Td 35.648148 Tz (1 ) Tj 0.447222 0 Td 49.907407 Tz (hour, ) Tj 1.652778 0 Td 46.990741 Tz (at ) Tj 0.7 0 Td 58.981481 Tz (which ) Tj 1.925 0 Td 51.203704 Tz (point ) Tj 51.428571 0 0 51.428571 0 2295.227621 Tm 6.358333 0 Td 39.969136 Tz (all ) Tj 0.991667 0 Td 50.501543 Tz (fluorescence ) Tj 3.888889 0 Td 55.555556 Tz (changes ) Tj 2.586111 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 58.333333 Tz (a ) Tj 0.583333 0 Td 50.231481 Tz (function ) Tj 2.702778 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 54.282407 Tz (time ) Tj 1.575 0 Td 58.333333 Tz (were ) Tj 1.652778 0 Td 42.12963 Tz (linear. ) Tj 51.428571 0 0 51.428571 0 2253.236908 Tm 6.377778 0 Td 53.20216 Tz (Fluorescence ) Tj 4.161111 0 Td 50.231481 Tz (readings ) Tj 2.702778 0 Td 59.143519 Tz (were ) Tj 1.75 0 Td 54.12037 Tz (normalized ) Tj 3.538889 0 Td 45.37037 Tz (to ) Tj 0.894444 0 Td 49.537037 Tz (vehicle ) Tj 2.333333 0 Td 49.074074 Tz (control ) Tj 40 0 0 40 0 2219 Tm 8.175 0 Td 58.333333 Tz (after ) Tj 1.9 0 Td 62.5 Tz (subtraction ) Tj 4.3 0 Td 70.833333 Tz (of ) Tj 0.925 0 Td 65.277778 Tz (fluorescence ) Tj 4.875 0 Td 58.333333 Tz (in ) Tj 0.85 0 Td 63.888889 Tz (the ) Tj 1.3 0 Td 70.833333 Tz (absence ) Tj 3.125 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 93.75 Tz (CCM. ) Tj 2.5 0 Td 71.875 Tz (Data ) Tj 40 0 0 40 0 2177 Tm 8.175 0 Td 63.888889 Tz (are ) Tj 1.4 0 Td 79.166667 Tz (shown ) Tj 2.625 0 Td 64.583333 Tz (as ) Tj 1.025 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 76.388889 Tz (meantS.D. ) Tj 4.375 0 Td 75 Tz (of ) Tj 1.025 0 Td 56.25 Tz (at ) Tj 0.925 0 Td 56.666667 Tz (least ) Tj 1.925 0 Td 62.5 Tz (three ) Tj 2.125 0 Td 59.722222 Tz (wells. ) Tj 51.428571 0 0 51.428571 0 2116.709317 Tm 7.116667 0 Td 59.143519 Tz (Each ) Tj 1.575 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 51.851852 Tz (nine ) Tj 1.380556 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 54.444444 Tz (determined ) Tj 3.402778 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 46.450617 Tz (effective ) Tj 2.625 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2075.563591 Tm 6.358333 0 Td 46.990741 Tz (inhibition ) Tj 3.130556 0 Td 53.703704 Tz (through ) Tj 2.605556 0 Td 48.611111 Tz (the ) Tj 1.186111 0 Td 57.118056 Tz (modeling ) Tj 3.072222 0 Td 59.953704 Tz (method ) Tj 2.45 0 Td 50.231481 Tz (delineated ) Tj 3.305556 0 Td 57.685185 Tz (above ) Tj 51.428571 0 0 51.428571 0 2035.68984 Tm 6.338889 0 Td 59.953704 Tz (were ) Tj 1.925 0 Td 54.73251 Tz (purchased ) Tj 3.422222 0 Td 57.523148 Tz (from ) Tj 1.886111 0 Td 62.546296 Tz (ChemBridge ) Tj 4.238889 0 Td 55.740741 Tz (under ) Tj 2.158333 0 Td 47.530864 Tz (the ) Tj 1.361111 0 Td 59.259259 Tz (numbers ) Tj 51.428571 0 0 51.428571 0 1992.745308 Tm 6.358333 0 Td 51.851852 Tz (assigned ) Tj 2.683333 0 Td 57.685185 Tz (above ) Tj 1.905556 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 47.222222 Tz (herein. ) Tj 51.428571 0 0 51.428571 0 1938.685315 Tm 7.097222 0 Td 75.833333 Tz (TABLE ) Tj 2.663889 0 Td 38.888889 Tz (1 ) Tj 0.602778 0 Td 52.256944 Tz (provides ) Tj 2.858333 0 Td 49.691358 Tz (the ) Tj 1.186111 0 Td 77.777778 Tz (ATX ) Tj 1.730556 0 Td 44.965278 Tz (activity ) Tj 2.527778 0 Td 49.907407 Tz (reductions ) Tj 3.344444 0 Td 42.12963 Tz (\(at ) Tj 1.147222 0 Td 56.712963 Tz (10 ) Tj 51.428571 0 0 51.428571 0 1896.344103 Tm 6.358333 0 Td 58.693416 Tz (micromole ) Tj 3.344444 0 Td 49.691358 Tz (concentrations\) ) Tj 4.666667 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 49.907407 Tz (these ) Tj 1.652778 0 Td 48.148148 Tz (assays. ) Tj 38.571429 0 0 38.571429 0 1815 Tm 18.251852 0 Td 101.111111 Tz (TABLE ) Tj 3.37037 0 Td 23.765432 Tz (1. ) Tj 31.428571 0 0 31.428571 0 1749 Tm 21.827273 0 Td 100.757576 Tz (ATX ) Tj 2.068182 0 Td 60.984848 Tz (Inhibition ) Tj 40 0 0 40 0 1680.406557 Tm 13.475 0 Td 67.708333 Tz (Compound ) Tj 8 0 Td 100 Tz (% ) Tj 0.75 0 Td 79.166667 Tz (ATX ) Tj 1.6 0 Td 48.958333 Tz (Activity ) Tj 36 0 0 36 0 1644.696721 Tm 16.027778 0 Td 71.759259 Tz (ID ) Tj 1.027778 0 Td 74.074074 Tz (# ) Tj 7.944444 0 Td 50.925926 Tz (at ) Tj 0.833333 0 Td 62.5 Tz (10 ) Tj 1.361111 0 Td 120.37037 Tz (M ) Tj 30 0 0 30 0 1587 Tm 18.433333 0 Td 80.15873 Tz (7839888 ) Tj 11.8 0 Td 77.777778 Tz (41 ) Tj 1.333333 0 Td 27.777778 Tz (- ) Tj 0.666667 0 Td 83.333333 Tz (9 ) Tj 30 0 0 30 0 1553 Tm 18.433333 0 Td 80.15873 Tz (SS64949 ) Tj 11.8 0 Td 80.555556 Tz (45 ) Tj 1.333333 0 Td 27.777778 Tz (- ) Tj 0.766667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 1520 Tm 18.433333 0 Td 79.365079 Tz (5711925 ) Tj 11.8 0 Td 137.037037 Tz (485 ) Tj 30 0 0 30 0 1487 Tm 18.433333 0 Td 80.15873 Tz (S186522 ) Tj 11.8 0 Td 83.333333 Tz (49 ) Tj 1.333333 0 Td 27.777778 Tz (- ) Tj 0.766667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 1454 Tm 18.433333 0 Td 79.365079 Tz (5761473 ) Tj 11.8 0 Td 83.333333 Tz (46 ) Tj 2.066667 0 Td 72.222222 Tz (6 ) Tj 30 0 0 30 0 1420 Tm 18.433333 0 Td 80.952381 Tz (SS38444 ) Tj 11.833333 0 Td 75 Tz (31 ) Tj 1.3 0 Td 27.777778 Tz (- ) Tj 0.7 0 Td 83.333333 Tz (4 ) Tj 30 0 0 30 0 1387 Tm 18.433333 0 Td 69.444444 Tz (79.21385 ) Tj 11.833333 0 Td 75 Tz (21 ) Tj 2.066667 0 Td 66.666667 Tz (6 ) Tj 30 0 0 30 0 1354 Tm 18.433333 0 Td 80.952381 Tz (5210574 ) Tj 11.833333 0 Td 135.185185 Tz (315 ) Tj 30 0 0 30 0 1321 Tm 18.433333 0 Td 80.15873 Tz (7905958 ) Tj 12.333333 0 Td 77.777778 Tz (O ) Tj 1.5 0 Td 83.333333 Tz (4 ) Tj 51.428571 0 0 51.428571 0 1200.827357 Tm 7.097222 0 Td 53.796296 Tz (Thus, ) Tj 1.886111 0 Td 34.027778 Tz (it ) Tj 0.7 0 Td 37.268519 Tz (is ) Tj 0.7 0 Td 51.388889 Tz (evident ) Tj 2.430556 0 Td 44.560185 Tz (that ) Tj 1.322222 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 49.331276 Tz (inventive ) Tj 2.897222 0 Td 61.934156 Tz (compounds ) Tj 3.597222 0 Td 48.611111 Tz (exhibit ) Tj 51.428571 0 0 51.428571 0 1160.850467 Tm 6.358333 0 Td 48.611111 Tz (excellent ) Tj 2.761111 0 Td 47.170782 Tz (potential ) Tj 2.702778 0 Td 49.691358 Tz (for ) Tj 0.991667 0 Td 50.411523 Tz (autotaxin ) Tj 2.877778 0 Td 45.868946 Tz (inactivation, ) Tj 3.713889 0 Td 46.990741 Tz (particularly ) Tj 3.538889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1120.014068 Tm 6.358333 0 Td 60.185185 Tz (7905958 ) Tj 2.644444 0 Td 64.409722 Tz (compound ) Tj 3.227778 0 Td 51.851852 Tz (with ) Tj 1.361111 0 Td 46.548822 Tz (essentially ) Tj 3.247222 0 Td 55.092593 Tz (no ) Tj 0.777778 0 Td 77.777778 Tz (ATX ) Tj 1.497222 0 Td 44.965278 Tz (activity ) Tj 2.313889 0 Td 50.636574 Tz (detected ) Tj 51.428571 0 0 51.428571 0 1079.525773 Tm 6.358333 0 Td 45.37037 Tz (at ) Tj 0.816667 0 Td 36.458333 Tz (all. ) Tj 1.186111 0 Td 55.092593 Tz (Coupled, ) Tj 2.916667 0 Td 48.611111 Tz (again, ) Tj 2.061111 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 48.611111 Tz (the ) Tj 1.166667 0 Td 46.990741 Tz (oral ) Tj 1.419444 0 Td 46.018519 Tz (bioavailability ) Tj 4.472222 0 Td 44.444444 Tz (results ) Tj 51.428571 0 0 51.428571 0 1037.603136 Tm 6.358333 0 Td 54.444444 Tz (noted ) Tj 1.769444 0 Td 52.932099 Tz (above, ) Tj 2.061111 0 Td 50.555556 Tz (these ) Tj 1.711111 0 Td 61.574074 Tz (compounds ) Tj 3.5 0 Td 69.135802 Tz (who ) Tj 1.4 0 Td 49.259259 Tz (great ) Tj 1.652778 0 Td 56.018519 Tz (promise ) Tj 2.508333 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 58.873457 Tz (provid ) Tj 51.428571 0 0 51.428571 0 993.854271 Tm 6.358333 0 Td 50.771605 Tz (ing ) Tj 1.127778 0 Td 46.450617 Tz (orally ) Tj 1.886111 0 Td 48.935185 Tz (ingestable ) Tj 3.111111 0 Td 58.981481 Tz (tumor ) Tj 1.905556 0 Td 50.555556 Tz (treatments ) Tj 3.227778 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 46.759259 Tz (certain ) Tj 2.177778 0 Td 48.206019 Tz (cancers. ) Tj 51.428571 0 0 51.428571 0 937.820513 Tm 7.097222 0 Td 56.388889 Tz (There ) Tj 1.925 0 Td 44.560185 Tz (are, ) Tj 1.322222 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 49.074074 Tz (course, ) Tj 2.352778 0 Td 64.814815 Tz (many ) Tj 1.808333 0 Td 46.254209 Tz (alternative ) Tj 3.247222 0 Td 59.806397 Tz (embodiments ) Tj 4.161111 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 897.050602 Tm 6.358333 0 Td 50.605413 Tz (modifications ) Tj 4.141667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 50.462963 Tz (present ) Tj 2.275 0 Td 50.411523 Tz (invention ) Tj 2.897222 0 Td 58.981481 Tz (which ) Tj 1.963889 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 52.256944 Tz (intended ) Tj 2.683333 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 855.700787 Tm 6.338889 0 Td 61.574074 Tz (be ) Tj 0.894444 0 Td 52.256944 Tz (included ) Tj 2.683333 0 Td 51.311728 Tz (within ) Tj 2.041667 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 41.589506 Tz (spirit ) Tj 1.633333 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 55.092593 Tz (scope ) Tj 1.827778 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 42.939815 Tz (this ) Tj 1.244444 0 Td 47.638889 Tz (invention. ) Tj 40 0 0 40 0 771 Tm 9.125 0 Td 84.375 Tz (What ) Tj 2.25 0 Td 91.666667 Tz (we ) Tj 1.3 0 Td 69.166667 Tz (claim ) Tj 2.325 0 Td 45.833333 Tz (is: ) Tj 51.428571 0 0 51.428571 0 710.622593 Tm 7.136111 0 Td 38.888889 Tz (1. ) Tj 0.641667 0 Td 84.259259 Tz (A ) Tj 0.661111 0 Td 64.00463 Tz (compound ) Tj 3.227778 0 Td 44.560185 Tz (that ) Tj 1.244444 0 Td 47.395833 Tz (exhibits ) Tj 2.45 0 Td 43.75 Tz (at ) Tj 0.7 0 Td 44.074074 Tz (least ) Tj 1.477778 0 Td 72.376543 Tz (50% ) Tj 1.477778 0 Td 50.05144 Tz (autotaxin ) Tj 2.897222 0 Td 52.932099 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 670.231579 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.458333 0 Td 47.638889 Tz (capability ) Tj 3.169444 0 Td 46.990741 Tz (at ) Tj 0.836111 0 Td 58.333333 Tz (a ) Tj 0.719444 0 Td 55.092593 Tz (10 ) Tj 1.186111 0 Td 66.435185 Tz (LM ) Tj 1.127778 0 Td 49.074074 Tz (concentration, ) Tj 4.452778 0 Td 48.611111 Tz (said ) Tj 1.458333 0 Td 64.814815 Tz (compound ) Tj 51.428571 0 0 51.428571 0 630.527578 Tm 6.358333 0 Td 49.259259 Tz (exhibiting ) Tj 3.072222 0 Td 43.75 Tz (at ) Tj 0.661111 0 Td 59.953704 Tz (most ) Tj 1.536111 0 Td 55.092593 Tz (5 ) Tj 0.486111 0 Td 59.683642 Tz (hydrogenbond ) Tj 4.452778 0 Td 50.925926 Tz (donors, ) Tj 2.255556 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 57.523148 Tz (most ) Tj 1.575 0 Td 55.092593 Tz (10 ) Tj 0.777778 0 Td 64.166667 Tz (hydro ) Tj 51.428571 0 0 51.428571 0 586.0199 Tm 6.358333 0 Td 57.253086 Tz (gen ) Tj 1.225 0 Td 62.384259 Tz (bond ) Tj 1.691667 0 Td 48.611111 Tz (acceptors, ) Tj 3.111111 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 45.37037 Tz (at ) Tj 0.758333 0 Td 59.143519 Tz (most ) Tj 1.652778 0 Td 56.712963 Tz (10 ) Tj 0.894444 0 Td 46.8107 Tz (rotatable ) Tj 2.702778 0 Td 58.333333 Tz (bonds ) Tj 1.963889 0 Td 45.775463 Tz (therein; ) Tj 51.428571 0 0 51.428571 0 544.35012 Tm 6.338889 0 Td 56.018519 Tz (wherein ) Tj 2.527778 0 Td 48.611111 Tz (said ) Tj 1.322222 0 Td 64.00463 Tz (compound ) Tj 3.227778 0 Td 48.148148 Tz (further ) Tj 2.158333 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 57.523148 Tz (from ) Tj 1.555556 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 56.388889 Tz (group ) Tj 1.866667 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 505.811254 Tm 6.377778 0 Td 45.37037 Tz (sisting ) Tj 2.002778 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 49.826389 Tz (thiourea ) Tj 2.527778 0 Td 64.00463 Tz (compound ) Tj 3.169444 0 Td 49.907407 Tz (exhibiting ) Tj 3.072222 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 53.292181 Tz (molecular ) Tj 2.994444 0 Td 55.632716 Tz (weight ) Tj 51.428571 0 0 51.428571 0 461.915094 Tm 6.358333 0 Td 52.662037 Tz (ofat ) Tj 1.4 0 Td 58.333333 Tz (most ) Tj 1.516667 0 Td 51.851852 Tz (527, ) Tj 1.361111 0 Td 56.712963 Tz (an ) Tj 0.836111 0 Td 48.611111 Tz (isoindole ) Tj 2.780556 0 Td 63.599537 Tz (compound ) Tj 3.169444 0 Td 49.259259 Tz (exhibiting ) Tj 3.033333 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 54.012346 Tz (molecular ) Tj 51.428571 0 0 51.428571 0 423.543307 Tm 6.338889 0 Td 56.17284 Tz (weight ) Tj 2.352778 0 Td 55.092593 Tz (of ) Tj 0.933333 0 Td 45.37037 Tz (at ) Tj 0.894444 0 Td 59.143519 Tz (most ) Tj 1.769444 0 Td 51.851852 Tz (648, ) Tj 1.575 0 Td 58.333333 Tz (a ) Tj 0.7 0 Td 51.851852 Tz (diphenyldiazerene ) Tj 5.638889 0 Td 49.259259 Tz (exhibiting ) Tj 3.305556 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 378.451146 Tm 6.358333 0 Td 54.372428 Tz (molecular ) Tj 3.072222 0 Td 55.092593 Tz (weight ) Tj 2.1 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 43.75 Tz (at ) Tj 0.7 0 Td 58.333333 Tz (most ) Tj 1.536111 0 Td 52.662037 Tz (500, ) Tj 1.4 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 51.851852 Tz (a ) Tj 0.466667 0 Td 55.092593 Tz (xanthene ) Tj 2.761111 0 Td 49.259259 Tz (exhibiting ) Tj 3.111111 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 337.486358 Tm 6.358333 0 Td 54.372428 Tz (molecular ) Tj 3.052778 0 Td 54.552469 Tz (weight ) Tj 2.080556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 57.523148 Tz (most ) Tj 1.516667 0 Td 51.851852 Tz (557; ) Tj 1.380556 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 55.092593 Tz (wherein ) Tj 2.45 0 Td 48.611111 Tz (said ) Tj 1.263889 0 Td 65.219907 Tz (compound ) Tj 51.428571 0 0 51.428571 0 295.88589 Tm 6.358333 0 Td 56.388889 Tz (meets ) Tj 1.905556 0 Td 39.969136 Tz (all ) Tj 0.913889 0 Td 55.092593 Tz (extended ) Tj 2.838889 0 Td 42.718855 Tz (flexibility ) Tj 3.072222 0 Td 49.537037 Tz (metrics ) Tj 2.275 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 48.287037 Tz (Lipinski's ) Tj 3.130556 0 Td 46.666667 Tz (rules ) Tj 1.633333 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 253.926366 Tm 6.338889 0 Td 48.611111 Tz (biological ) Tj 3.072222 0 Td 44.871795 Tz (distribution, ) Tj 3.636111 0 Td 55.555556 Tz (wherein ) Tj 2.508333 0 Td 47.800926 Tz (said ) Tj 1.263889 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 44.722222 Tz (least ) Tj 1.477778 0 Td 57.253086 Tz (one ) Tj 1.166667 0 Td 64.00463 Tz (compound ) Tj 3.188889 0 Td 40.509259 Tz (is ) Tj 51.428571 0 0 51.428571 0 212.569501 Tm 6.377778 0 Td 48.611111 Tz (selected ) Tj 2.663889 0 Td 56.712963 Tz (from ) Tj 1.691667 0 Td 50.771605 Tz (the ) Tj 1.225 0 Td 55.740741 Tz (group ) Tj 2.002778 0 Td 49.259259 Tz (consisting ) Tj 3.286111 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 45.37037 Tz (at ) Tj 0.875 0 Td 44.074074 Tz (least ) Tj 1.652778 0 Td 57.253086 Tz (one ) Tj 1.341667 0 Td 58.333333 Tz (of ) Tj 0.933333 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 176 Tm 6.358333 0 Td 49.583333 Tz (following: ) Tj 31.428571 0 0 31.428571 0 2879 Tm 68.822727 0 Td 111.363636 Tz (C ) Tj 30 0 0 30 0 2755 Tm 41.833333 0 Td 72.222222 Tz (5 ) Tj 135.714286 0 0 135.714286 0 2665 Tm 11.391579 0 Td 23.333333 Tz (\( ) Tj 0.751579 0 Td 51.169591 Tz (\)-\( ) Tj 1.422105 0 Td 53.216374 Tz (\)-\( ) Tj 49.285714 0 0 49.285714 0 2653.113402 Tm 35.426087 0 Td 104.830918 Tz (\\ ) Tj 1.805797 0 Td 104.830918 Tz (/ ) Tj 2.637681 0 Td 47.342995 Tz (S ) Tj 4.017391 0 Td 71.014493 Tz (C ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 31.428571 0 0 31.428571 0 2432 Tm 54.027273 0 Td 76.515152 Tz (7905958 ) Tj 31.428571 0 0 31.428571 0 2365 Tm 44.672727 0 Td 111.363636 Tz (OH ) Tj 21.254545 0 Td 111.363636 Tz (O ) Tj 39.52381 0 0 39.52381 0 2322.150685 Tm 31.626506 0 Td 54.819277 Tz (15 ) Tj 2.024096 0 Td 71.686747 Tz (O ) Tj 5.161446 0 Td 88.554217 Tz (O ) Tj 5.161446 0 Td 88.554217 Tz (O ) Tj 5.161446 0 Td 88.554217 Tz (O ) Tj 5.186747 0 Td 84.337349 Tz (OH ) Tj 230 0 0 230 0 2170 Tm 6.982609 0 Td 85.748792 Tz (oo: ) Tj 40.571429 0 0 40.571429 0 2140.775862 Tm 31.105634 0 Td 49.295775 Tz (o ) Tj 1.158451 0 Td 84.213615 Tz (HO ) Tj 5.545775 0 Td 86.267606 Tz (O ) Tj 10.056338 0 Td 86.267606 Tz (O ) Tj 5.052817 0 Td 86.267606 Tz (O ) Tj 31.428571 0 0 31.428571 0 2103 Tm 44.672727 0 Td 111.363636 Tz (O ) Tj 20.65 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2052 Tm 54.409091 0 Td 77.272727 Tz (5186522 ) Tj 31.428571 0 0 31.428571 0 1966 Tm 61.822727 0 Td 95.454545 Tz (O ) Tj 105 0 0 105 0 1839.652482 Tm 11.885714 0 Td 22.222222 Tz (25 ) Tj 5.238095 0 Td 179.365079 Tz (C ) Tj 31.428571 0 0 31.428571 0 1755 Tm 65.513636 0 Td 95.454545 Tz (O ) Tj 94.285714 0 0 94.285714 0 1657.090909 Tm 13.236364 0 Td 25.631313 Tz (30 ) Tj 7.084848 0 Td 71.590909 Tz (1. ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30.714286 0 0 30.714286 0 1301.312977 Tm 40.6 0 Td 81.395349 Tz (40 ) Tj 14.683721 0 Td 78.294574 Tz (7839888 ) Tj 31.428571 0 0 31.428571 0 1235 Tm 65.959091 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1191 Tm 68.345455 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1117 Tm 55.3 0 Td 95.454545 Tz (O ) Tj 30.952381 0 0 30.952381 0 1096.915493 Tm 40.287692 0 Td 78.076923 Tz (45 ) Tj 9.272308 0 Td 113.076923 Tz (O ) Tj 13.181538 0 Td 113.076923 Tz (O ) Tj 141.428571 0 0 141.428571 0 978 Tm 10.917172 0 Td 97.811448 Tz (CO?CO ) Tj 31.428571 0 0 31.428571 0 932 Tm 48.809091 0 Td 111.363636 Tz (O ) Tj 12.981818 0 Td 111.363636 Tz (O ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 31.428571 0 0 31.428571 0 842 Tm 41.65 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 798 Tm 44.672727 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 749 Tm 54.409091 0 Td 76.515152 Tz (5761473 ) Tj 101.428571 0 0 101.428571 0 596.951515 Tm 12.304225 0 Td 23.004695 Tz (55 ) Tj 7.926761 0 Td 112.558685 Tz (JO ) Tj 31.428571 0 0 31.428571 0 602 Tm 48.745455 0 Td 111.363636 Tz (O ) Tj 14.063636 0 Td 121.969697 Tz (N ) Tj 41.428571 0 0 41.428571 0 575.957746 Tm 42.675862 0 Td 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