Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model

doi:10.1021/acs.jmedchem.9b01895

	Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model
	Zhao, Jihui 2,5; Cui, Rongrong 2,3; Wang, Lihao 2,6; Chen, Yingjia 2; Fu, Zunyun 2,3; Ding, Xiaoyu 2; Cui, Chen 2; Yang, Tianbiao 2; Li, Xutong 2; Xu, Yuan 2,7
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2020-06-25
卷号	63 期号:12 页码:6523-6537
ISSN号	0022-2623
DOI	10.1021/acs.jmedchem.9b01895
通讯作者	Jiang, Hualiang(hljiang@simm.ac.cn) ; Zheng, Mingyue(myzheng@simm.ac.cn)
英文摘要	Aldehyde oxidase (AOX) is a drug metabolizing molybdo-flavoenzyme that has gained increasing attention because of contribution to the biotransformation in phase I metabolism of xenobiotics. Unfortunately, the intra- and interspecies variations in AOX activity and lack of reliable and predictive animal models make evaluation of AOX-catalyzed metabolism prone to be misleading. In this study, we developed an improved computational model integrating both atom-level and molecule-level features to predict whether a drug-like molecule is a potential human AOX (hAOX) substrate and to identify the corresponding sites of metabolism. Additionally, we combined the proposed computational strategy and in vitro experiments for evaluating the metabolic property of a series of epigenetic-related drug candidates still in the early stage of development. In summary, this study provides an improved strategy to evaluate the liability of molecules toward hAOX and offers useful information for accelerating the drug design and optimization stage.
资助项目	National Natural Science Foundation of China[81773634] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Molecular Signature-Based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050201]
WOS关键词	REACTIVITY ; PREDICTION ; INHIBITOR ; MECHANISM ; INSIGHTS ; SITE ; DISCOVERY ; POTENT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000545660500016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291851]
专题	中国科学院上海药物研究所
通讯作者	Jiang, Hualiang; Zheng, Mingyue
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Univ N Carolina, Gillings Sch Publ Hlth, Chapel Hill, NC 27599 USA 7.Shanghai EnnovaBio Pharmaceut Co Ltd, Shanghai 200120, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Jihui,Cui, Rongrong,Wang, Lihao,et al. Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model[J]. JOURNAL OF MEDICINAL CHEMISTRY,2020,63(12):6523-6537.
APA	Zhao, Jihui.,Cui, Rongrong.,Wang, Lihao.,Chen, Yingjia.,Fu, Zunyun.,...&Zheng, Mingyue.(2020).Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model.JOURNAL OF MEDICINAL CHEMISTRY,63(12),6523-6537.
MLA	Zhao, Jihui,et al."Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model".JOURNAL OF MEDICINAL CHEMISTRY 63.12(2020):6523-6537.