Research Article
Novel Design Strategy for Checkpoint Kinase 2 Inhibitors Using Pharmacophore Modeling, Combinatorial Fusion, and Virtual Screening
Table 2
Experimental and estimated IC50 values of testing set inhibitors.
| | CHEMBL ID | Experimental
IC50 (nM) | Estimated IC50 (nM) | | Besttrain | Fasttrain | BesttrainBesttest + FasttrainFasttest | | Besttest | Fasttest | Caesartest | Besttest | Fasttest | Caesartest |
| | CHEMBL195177 | 3.4 | 3.9 | 5.2 | 5.1 | 14.8 | 6.2 | 12.3 | 6.2 | | CHEMBL359881 | 4.4 | 12.0 | 46.1 | 42.3 | 17.3 | 22.5 | 29.4 | 22.5 | | CHEMBL179717 | 4.5 | 9.0 | 42.1 | 43.2 | 14.3 | 21.9 | 29.3 | 21.9 | | CHEMBL175553 | 5.5 | 11.2 | 57.8 | 43.1 | 17.6 | 20.5 | 29.1 | 20.5 | | CHEMBL192161 | 7 | 183.4 | 74.6 | 36.7 | 258.7 | 253.9 | 291.4 | 253.9 | | CHEMBL191969 | 8.2 | 6.4 | 15.3 | 14.3 | 10.5 | 9.4 | 13.5 | 9.4 | | CHEMBL175472 | 9.8 | 7.9 | 48.4 | 9.9 | 12.4 | 22.5 | 29.1 | 22.5 | | CHEMBL361378 | 12 | 9.9 | 48.1 | 43.7 | 14.7 | 21.7 | 29.3 | 21.7 | | CHEMBL362255 | 12 | 11.9 | 55.4 | 42.3 | 15.5 | 22.9 | 29.4 | 22.9 | | CHEMBL369254 | 12 | 70.2 | 51.3 | 45.6 | 38.0 | 23.7 | 31.5 | 23.7 | | CHEMBL364978 | 13 | 4.8 | 4.9 | 5.1 | 13.5 | 6.5 | 12.3 | 6.5 | | CHEMBL195846 | 14 | 3.9 | 5.0 | 5.1 | 12.8 | 6.2 | 12.3 | 6.2 | | CHEMBL179583 | 16 | 12.2 | 48.5 | 43.1 | 13.4 | 23.2 | 28.9 | 23.2 | | CHEMBL178972 | 17 | 15.9 | 52.5 | 43.1 | 18.0 | 23.3 | 29.1 | 23.3 | | CHEMBL250360 | 23 | 19.8 | 46.8 | 43.7 | 17.6 | 21.7 | 29.4 | 21.7 | | CHEMBL175879 | 24 | 21.6 | 57.0 | 42.3 | 24.0 | 23.2 | 29.2 | 23.2 | | CHEMBL179267 | 31 | 7.4 | 63.5 | 42.8 | 20.5 | 21.2 | 29.4 | 21.2 | | CHEMBL192022 | 32 | 20.3 | 47.5 | 42.6 | 23.9 | 22.4 | 29.4 | 22.4 | | CHEMBL250158 | 39 | 10.1 | 20.4 | 43.7 | 19.1 | 21.5 | 29.3 | 21.5 | | CHEMBL363339 | 41 | 10.1 | 59.8 | 42.2 | 18.1 | 24.0 | 29.5 | 24.0 | | CHEMBL250555 | 45 | 26.3 | 48.2 | 42.9 | 24.5 | 22.7 | 29.4 | 22.7 | | CHEMBL250359 | 52 | 3.7 | 5.2 | 3.5 | 20.6 | 7.0 | 28.8 | 7.0 | | CHEMBL251585 | 52 | 4.5 | 3.0 | 3.1 | 11.9 | 4.9 | 10.7 | 4.9 | | CHEMBL398529 | 53 | 23.0 | 48.4 | 43.5 | 21.4 | 22.4 | 29.4 | 22.4 | | CHEMBL178971 | 55 | 62.4 | 44.9 | 43.1 | 41.7 | 22.1 | 29.3 | 22.1 | | CHEMBL427879 | 55 | 13.7 | 45.4 | 42.4 | 16.9 | 19.9 | 29.5 | 19.9 | | CHEMBL250963 | 57 | 8.6 | 44.1 | 42.9 | 17.8 | 21.5 | 27.2 | 21.5 | | CHEMBL251170 | 60 | 51.3 | 45.3 | 43.1 | 26.3 | 21.5 | 29.4 | 21.5 | | CHEMBL250759 | 61 | 45.6 | 47.4 | 43.3 | 36.6 | 23.2 | 29.5 | 23.2 | | CHEMBL367263 | 61 | 19.7 | 50.3 | 9.6 | 17.3 | 23.9 | 29.1 | 23.9 | | CHEMBL250159 | 67 | 55.7 | 45.3 | 43.1 | 25.7 | 17.2 | 29.4 | 17.2 | | CHEMBL398467 | 70 | 11.4 | 46.5 | 42.7 | 21.0 | 20.4 | 29.4 | 20.4 | | CHEMBL250796 | 73 | 3.3 | 3.4 | 4.2 | 14.7 | 6.0 | 14.4 | 6.0 | | CHEMBL250957 | 74 | 36.1 | 44.9 | 43.7 | 30.5 | 20.4 | 29.5 | 20.4 | | CHEMBL206609 | 77 | 25.9 | 51.0 | 44.0 | 9.6 | 16.3 | 17.8 | 16.3 | | CHEMBL400755 | 78 | 8.8 | 26.6 | 43.0 | 12.9 | 22.5 | 29.4 | 22.5 | | CHEMBL249569 | 80 | 11.1 | 48.3 | 43.3 | 17.0 | 22.9 | 28.0 | 22.9 | | CHEMBL193397 | 81 | 9.9 | 43.8 | 42.8 | 14.5 | 21.2 | 28.4 | 21.2 | | CHEMBL438868 | 82 | 18.9 | 42.0 | 43.1 | 13.1 | 19.0 | 29.3 | 19.0 | | CHEMBL249566 | 86 | 17.6 | 48.8 | 43.1 | 23.5 | 22.8 | 29.6 | 22.8 | | CHEMBL249345 | 90 | 23.2 | 47.6 | 43.0 | 20.9 | 20.0 | 25.0 | 20.0 | | CHEMBL399146 | 90 | 29.8 | 47.9 | 42.7 | 28.4 | 22.1 | 29.3 | 22.1 | | CHEMBL602931 | 92 | 483.6 | 560.1 | 506.8 | 645.9 | 594.0 | 588.2 | 594.0 | | CHEMBL249347 | 95 | 10.1 | 46.3 | 43.1 | 27.2 | 20.1 | 29.2 | 20.1 | | CHEMBL193476 | 100 | 951.1 | 914.5 | 925.8 | 2435.2 | 1027.4 | 1981.9 | 1027.4 | | CHEMBL250361 | 100 | 14.2 | 6.6 | 14.5 | 14.9 | 20.9 | 29.6 | 20.9 | | CHEMBL248934 | 109 | 20.0 | 52.5 | 43.3 | 14.0 | 22.4 | 29.4 | 22.4 | | CHEMBL249750 | 110 | 12.7 | 49.3 | 43.5 | 20.7 | 21.6 | 29.3 | 21.6 | | CHEMBL208463 | 133 | 10.4 | 46.0 | 41.0 | 968.6 | 2768.3 | 2670.7 | 2768.3 | | CHEMBL250566 | 140 | 5.2 | 17.3 | 26.3 | 18.4 | 20.9 | 29.6 | 20.9 | | CHEMBL251256 | 140 | 936.4 | 2453.5 | 2240.6 | 192.6 | 215.1 | 215.5 | 215.1 | | CHEMBL437331 | 142 | 471.8 | 521.6 | 450.6 | 64.2 | 222.1 | 60.7 | 222.1 | | CHEMBL249541 | 157 | 23.8 | 42.5 | 43.0 | 16.0 | 18.8 | 29.3 | 18.8 | | CHEMBL249776 | 158 | 13.9 | 47.2 | 43.7 | 16.7 | 20.9 | 29.4 | 20.9 | | CHEMBL249350 | 174 | 30.6 | 51.2 | 43.4 | 22.5 | 23.3 | 29.4 | 23.3 | | CHEMBL249546 | 176 | 10.6 | 47.3 | 42.8 | 17.9 | 21.0 | 29.4 | 21.0 | | CHEMBL251364 | 176 | 21.7 | 43.9 | 43.1 | 17.8 | 19.7 | 29.1 | 19.7 | | CHEMBL399933 | 180 | 14.8 | 45.0 | 43.5 | 20.8 | 18.9 | 29.4 | 18.9 | | CHEMBL400287 | 180 | 19.3 | 45.5 | 43.5 | 21.5 | 19.8 | 29.4 | 19.8 | | CHEMBL175780 | 200 | 61.7 | 47.5 | 42.3 | 36.0 | 21.9 | 29.5 | 21.9 | | CHEMBL176326 | 200 | 935.6 | 926.3 | 913.6 | 1896.0 | 986.2 | 1980.7 | 986.2 | | CHEMBL590335 | 210 | 791.5 | 721.8 | 807.4 | 616.3 | 639.0 | 644.7 | 639.0 | | CHEMBL398561 | 220 | 575.1 | 926.2 | 571.5 | 209.1 | 278.3 | 287.9 | 278.3 | | CHEMBL249777 | 231 | 15.0 | 45.7 | 42.5 | 25.5 | 21.7 | 29.4 | 21.7 | | CHEMBL442282 | 233 | 13.9 | 46.9 | 42.3 | 21.5 | 22.5 | 29.4 | 22.5 | | CHEMBL195599 | 250 | 981.5 | 908.0 | 925.8 | 2266.7 | 1057.6 | 1981.9 | 1057.6 | | CHEMBL176015 | 290 | 54.1 | 52.8 | 54.4 | 24.0 | 29.3 | 28.0 | 29.3 | | CHEMBL251284 | 310 | 484.8 | 429.7 | 533.7 | 189.6 | 196.8 | 217.4 | 196.8 | | CHEMBL600441 | 310 | 454.6 | 559.9 | 516.5 | 300.5 | 513.5 | 254.1 | 513.5 | | CHEMBL599581 | 410 | 594.7 | 496.6 | 509.1 | 506.1 | 252.9 | 299.2 | 252.9 | | CHEMBL592784 | 420 | 462.2 | 492.0 | 475.1 | 216.7 | 203.8 | 198.3 | 203.8 | | CHEMBL1197465 | 580 | 2492.8 | 8163.9 | 5925.9 | 995.1 | 896.8 | 488.9 | 896.8 | | CHEMBL590809 | 600 | 492.4 | 539.0 | 534.3 | 816.4 | 536.2 | 549.3 | 536.2 | | CHEMBL1197456 | 610 | 2871.8 | 7537.6 | 6733.2 | 615.7 | 4139.2 | 3514.6 | 4139.2 | | CHEMBL590637 | 610 | 1251.9 | 1786.7 | 1121.1 | 2379.0 | 1650.9 | 1262.3 | 1650.9 | | CHEMBL591518 | 680 | 1797.9 | 1804.0 | 1516.5 | 6075.0 | 4714.4 | 2726.5 | 4714.4 | | CHEMBL598973 | 700 | 12585.6 | 151896.0 | 84151.4 | 1047.3 | 396.5 | 1318.1 | 396.5 | | CHEMBL251368 | 710 | 27.7 | 45.9 | 43.8 | 13.4 | 21.2 | 29.1 | 21.2 | | CHEMBL1197303 | 800 | 5153.6 | 36481.1 | 6594.4 | 1277.8 | 681.9 | 4077.9 | 681.9 | | CHEMBL1197320 | 890 | 2537.8 | 7191.1 | 6002.7 | 1559.4 | 517.5 | 420.0 | 517.5 | | CHEMBL1197528 | 960 | 2752.7 | 7737.1 | 5925.9 | 765.7 | 654.9 | 559.0 | 654.9 | | CHEMBL215803 | 1000 | 3760.6 | 140257.0 | 74847.0 | 9672.7 | 50053.5 | 49263.9 | 50053.5 | | CHEMBL253324 | 1000 | 996.2 | 2416.5 | 603.1 | 264.7 | 553.1 | 272.4 | 553.1 | | CHEMBL589347 | 1100 | 458.3 | 560.2 | 482.3 | 209.7 | 299.1 | 196.7 | 299.1 | | CHEMBL604784 | 1100 | 1188.4 | 1365.6 | 1205.7 | 2305.3 | 1962.3 | 1307.9 | 1962.3 | | CHEMBL1197529 | 1120 | 2047.4 | 11678.5 | 8090.0 | 3368.8 | 3648.8 | 3659.9 | 3648.8 | | CHEMBL1197326 | 1130 | 12645.5 | 45428.8 | 7432.7 | 1138.2 | 465.0 | 416.0 | 465.0 | | CHEMBL176041 | 1200 | 925.0 | 906.8 | 913.6 | 1933.6 | 1040.0 | 1980.7 | 1040.0 | | CHEMBL590079 | 1350 | 548.9 | 548.5 | 550.6 | 1000.9 | 860.3 | 855.1 | 860.3 | | CHEMBL605083 | 1400 | 489.2 | 613.8 | 554.4 | 1224.9 | 1401.0 | 1345.6 | 1401.0 | | CHEMBL175481 | 1500 | 69.2 | 57.7 | 49.2 | 1853.9 | 1526.1 | 1852.1 | 1526.1 | | CHEMBL205906 | 1540 | 1696.1 | 1109.3 | 1153.0 | 980.6 | 17655.5 | 937.5 | 17655.5 | | CHEMBL590808 | 1600 | 1662.5 | 1799.1 | 1709.4 | 51882.2 | 48813.2 | 48302.3 | 48813.2 | | CHEMBL1170748 | 1700 | 1974.2 | 1940.4 | 1652.8 | 3251.4 | 2734.9 | 407.6 | 2734.9 | | CHEMBL253541 | 1800 | 43066.9 | 42831.1 | 79622.8 | 1255.9 | 1099.1 | 15566.3 | 1099.1 | | CHEMBL176554 | 1900 | 572.3 | 7226.3 | 9126.2 | 1096.1 | 3352.6 | 3926.3 | 3352.6 | | CHEMBL377597 | 2000 | 938.5 | 6719.7 | 5644.6 | 50.4 | 116.9 | 105.4 | 116.9 | | CHEMBL1170749 | 2200 | 10874.0 | 30873.8 | 3995.6 | 5835.1 | 25044.3 | 1090.5 | 25044.3 | | CHEMBL590336 | 2200 | 507.8 | 594.0 | 516.4 | 568.9 | 544.3 | 521.1 | 544.3 | | CHEMBL590807 | 2200 | 52944.6 | 70480.3 | 52639.4 | 44898.4 | 49196.7 | 36195.2 | 49196.7 | | CHEMBL600868 | 2200 | 1342.8 | 1603.8 | 1312.9 | 7373.6 | 5797.7 | 4864.3 | 5797.7 | | CHEMBL398759 | 2300 | 666.0 | 2847.2 | 1010.2 | 447.2 | 924.3 | 309.0 | 924.3 | | CHEMBL604459 | 2300 | 1176.9 | 2299.2 | 1369.3 | 614.2 | 877.8 | 682.5 | 877.8 | | CHEMBL179383 | 2400 | 15724.9 | 14621.7 | 14257.4 | 4508.5 | 4132.8 | 4023.9 | 4132.8 | | CHEMBL592489 | 2400 | 469.2 | 494.6 | 486.9 | 204.7 | 240.5 | 208.4 | 240.5 | | CHEMBL425904 | 2800 | 605.0 | 651.0 | 534.9 | 478.1 | 451.9 | 488.6 | 451.9 | | CHEMBL150894 | 3000 | 537.8 | 844.9 | 797.6 | 186.8 | 600.2 | 289.0 | 600.2 | | CHEMBL590793 | 3000 | 475.4 | 2480.4 | 1251.5 | 192.0 | 251.7 | 205.4 | 251.7 | | CHEMBL600865 | 4400 | 796.9 | 2072.3 | 1223.3 | 198.1 | 261.3 | 228.1 | 261.3 | | CHEMBL249253 | 5000 | 659.8 | 503.6 | 499.5 | 406.6 | 227.9 | 309.5 | 227.9 | | CHEMBL587506 | 5200 | 1050.8 | 1293.3 | 1083.2 | 2201.3 | 2162.7 | 1656.0 | 2162.7 | | CHEMBL204930 | 5800 | 755.5 | 1260.7 | 1105.5 | 47881.6 | 47912.3 | 47868.0 | 47912.3 | | CHEMBL554900 | 5900 | 6722.8 | 580526.0 | 807309.0 | 745.4 | 428.2 | 47897.1 | 428.2 | | CHEMBL176276 | 6000 | 3360.2 | 8955.9 | 8476.6 | 2075.6 | 2054.0 | 1970.7 | 2054.0 | | CHEMBL589091 | 6100 | 1319.5 | 1308.4 | 1172.0 | 579.2 | 603.1 | 600.9 | 603.1 | | CHEMBL559781 | 7400 | 91783.7 | 822917.0 | 1230010.0 | 414.5 | 6865.5 | 47911.9 | 6865.5 | | CHEMBL249252 | 8000 | 100671.0 | 38586.8 | 31129.8 | 590.5 | 491.6 | 467.9 | 491.6 | | CHEMBL589089 | 9800 | 1070.7 | 1321.5 | 1002.7 | 38589.3 | 48136.2 | 41143.2 | 48136.2 | | CHEMBL217090 | 10000 | 628.8 | 1010.9 | 1548.5 | 390.6 | 451.8 | 910.1 | 451.8 | | CHEMBL217092 | 10000 | 1030.2 | 1199.3 | 1908.8 | 379.9 | 625.6 | 707.2 | 625.6 | | CHEMBL382588 | 10000 | 1365.2 | 5880.3 | 5488.7 | 2560.7 | 3993.4 | 3649.4 | 3993.4 | | CHEMBL590581 | 10000 | 145206.0 | 149922.0 | 108067.0 | 50609.5 | 49348.5 | 48302.3 | 49348.5 | | CHEMBL242753 | 10300 | 1742.5 | 3393.1 | 1941.1 | 1202.5 | 2613.0 | 1297.3 | 2613.0 | | CHEMBL398758 | 11000 | 1582.8 | 187965.0 | 1573.6 | 237.0 | 4333.9 | 369.0 | 4333.9 | | CHEMBL399151 | 11000 | 812.1 | 1263.5 | 2069.9 | 334.5 | 1193.9 | 1271.6 | 1193.9 | | CHEMBL395080 | 13450 | 513.5 | 484.0 | 458.6 | 198.5 | 188.9 | 183.3 | 188.9 | | CHEMBL1171533 | 15000 | 349604.0 | 296515.0 | 159368.0 | 26784.5 | 26699.3 | 45506.4 | 26699.3 | | CHEMBL602729 | 17000 | 148756.0 | 149052.0 | 139465.0 | 224.1 | 324.7 | 229.4 | 324.7 | | CHEMBL249255 | 19000 | 182486.0 | 42615.8 | 41578.3 | 1698.2 | 616.1 | 683.9 | 616.1 | | CHEMBL202930 | 21730 | 12828.4 | 11945.6 | 12145.8 | 213.3 | 219.7 | 217.6 | 219.7 | | CHEMBL589986 | 22000 | 1167.1 | 1337.4 | 1143.5 | 53747.5 | 49155.6 | 49316.8 | 49155.6 | | CHEMBL251471 | 40000 | 3358.9 | 1946.2 | 2075.7 | 512.2 | 423.7 | 3427.4 | 423.7 | | CHEMBL560056 | 74000 | 152006.0 | 156723.0 | 208466.0 | 223.2 | 208.1 | 190.4 | 208.1 |
| Correlation
coefficient | | 0.810 | 0.771 | 0.783 | 0.710 | 0.728 | 0.714 | 0.816 |
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