Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: A Combined Computational and Experimental Study
文献类型：期刊论文
| 作者 | Xu, Yuan1,2; Li, Liang1 ; Wang, Yulan1,2; Xing, Jing1,2; Zhou, Lei1,2; Zhong, Dafang1; Luo, Xiaomin1; Jiang, Hualiang1; Chen, Kaixian1; Zheng, Mingyue1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2017-04-13 |
| 卷号 | 60期号:7页码:2973-2982 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.7b00019 |
| 文献子类 | Article |
| 英文摘要 | Aldehyde oxidase (AOX) is an important drug-metabolizing enzyme. However, the current in vitro models for evaluating AOX metabolism are sometimes misleading, and preclinical animal models generally fail to predict human AOX-mediated metabolism. In this study, we report a combined computational and experimental investigation of drug-like molecules that are potential aldehyde oxidase substrates, of which multiple sites of metabolism (SOMs) mediated by AOX and their preferences for the reaction can be unambiguously identified. In addition, the proposed strategy was used to evaluate the metabolism of newly designed c-Met inhibitors, and a success switch-off of AOX metabolism was observed. Overall, this study provide useful information to guide lead optimization and drug discovery based on AOX-mediated metabolism. |
| WOS关键词 | RENAL TOXICITY ; MET INHIBITOR ; DISCOVERY ; KINASE ; ZONIPORIDE ; FRACTIONS ; CANCER ; MONKEY ; SGX523 ; RATS |
| 资助项目 | National Natural Science Foundation of China[81573500] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050201] ; National Key Research & Development (RD) Plan[2016YF1201003] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000399436100024 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272703]  |
| 专题 | 药物发现与设计中心 上海药物代谢研究中心 |
| 通讯作者 | Zheng, Mingyue; Deng, Pan; Chen, Xiaoyan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Yuan,Li, Liang,Wang, Yulan,et al. Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: A Combined Computational and Experimental Study[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60(7):2973-2982. |
| APA | Xu, Yuan.,Li, Liang.,Wang, Yulan.,Xing, Jing.,Zhou, Lei.,...&Chen, Xiaoyan.(2017).Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: A Combined Computational and Experimental Study.JOURNAL OF MEDICINAL CHEMISTRY,60(7),2973-2982. |
| MLA | Xu, Yuan,et al."Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: A Combined Computational and Experimental Study".JOURNAL OF MEDICINAL CHEMISTRY 60.7(2017):2973-2982. |
入库方式： OAI收割
来源：上海药物研究所
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