The Pharmacophore Hypothesis of Novel Inhibitors for Aurora A Kinase

• 来源期刊: 中国化学（英文版）
• 年，卷（期）: 2007,（12）
• 页码范围: 1911-1918
• 页数: 8页
• 语种: 英文

摘要

A three-dimensional pharmacophore model was developed from a series of inhibitors of Aurora A kinase to discover new potent anti-cancer agents using the HypoGen module in the Catalyst software.The pharmacophore model was developed based on the structure of 20 currently available inhibitors,which were carefully selected from the literature.The best hypothesis (Hypo 1) was defined by four features: one hydrogen-bond donor and three hy-drophobic points,with the best correlation coefficient of 0.909,the lowest rms deviation of 1.563,and the highest cost difference of 99.075.The Hypo 1 was then validated by a test set consisting of 24 compounds and by a cross-validation of 95% confidence level through randomizing the data using the CatScramble program,which suggested that a predictive pharmacophore model had been successfully obtained.