| The Pharmacophore Hypothesis of Novel Inhibitors for Aurora A Kinase |
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| 作者姓名： | 汪小涧 陈亚东 杨倩 尤启冬 |
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| 作者单位： | Department of Medicinal Chemistry China Pharmaceutical University, Nanjing, Jiangsu 210009, China |
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| 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.
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| 关 键 词： | Aurora A激酶 药效 测试结构 药物 |
| 收稿时间： | 2007-05-09 |
| 修稿时间： | 2007-07-04 |
The Pharmacophore Hypothesis of Novel Inhibitors for Aurora A Kinase |
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| WANG, Xiao-Jian CHEN, Ya-Dong YANG, Qian YOU, Qi-Dong.The Pharmacophore Hypothesis of Novel Inhibitors for Aurora A Kinase[J].Chinese Journal of Chemistry,2007,25(12):1911-1918. |
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| Authors: | WANG Xiao-Jian CHEN Ya-Dong YANG Qian YOU Qi-Dong |
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| Institution: | 1. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China;2. Tel.: 0086‐025‐83271351;3. Fax: 0086‐025‐83271351 |
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| Abstract: | 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 l) was defined by four features: one hydrogen‐bond donor and three hydrophobic 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. |
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| Keywords: | Aurora A kinase pharmacophore hypothesis training set test set cross validation |
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