Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay

被引：39

作者：

Al-Sha'er, Mahmoud A. ^{[1
]}

Taha, Mutasem O. ^{[1
]}

机构：

[1] Univ Jordan, Drug Discovery Unit, Dept Pharmaceut Sci, Fac Pharm, Amman, Jordan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 09期

关键词：

CDK1; Cancer; Pharmacophore modeling; QSAR; Genetic algorithm; MLR; In silico screening; KINASE INHIBITORS; DRUG DESIGN; POTENT; IDENTIFICATION; DATABASE; DERIVATIVES; HORMONE; DOCKING; BINDING; QSPR;

D O I：

10.1016/j.ejmech.2010.06.034

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cyclin-dependent kinase 1 (CDK1) is a valid anticancer target. With this in mind we applied a modeling workflow by combining pharmacophore modeling and QSAR analysis followed by in silico screening towards the discovery of novel inhibitory CDK1 scaffolds. Virtual screening identified 10 low micromolar inhibitory leads: 8 from the National Caner Institute (NCI) list of compounds and 2 from our in house list of established drugs and agrochemicals. The most potent NCI hit illustrated anti-CDK1 IC50 value of 0.83 mu M, while the drug hit isoxsuprine illustrated anti-CDK1 IC50 value of 2.9 mu M and the agrochemical hit foramsulfuran showed IC50 = 3.6 mu M. These results demonstrate that our virtual screening protocol is able to identify novel anti-CDK1 leads for subsequent development into potential anticancer agents. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：4316 / 4330

页数：15

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