Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening

doi:10.1016/j.bmcl.2019.126823

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening
	Weng, Zhiying 3,4; Xu, Guowei 1; Chen, Dingyuan 1; Yang, Yaqing 3,4; Song, Gao 3,4; Shen, Wen 2; Zhang, Shuqun 1; Wang, LiangLiang 1; Yang, Weimin 3,4; Zuo, Zhili 1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2020-01-15
卷号	30 期号:2 页码:7
关键词	Adenylyl cyclases Homology modeling Consensus scoring Molecular dynamics simulation Virtual screening Biological evaluation
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2019.126823
通讯作者	Yang, Weimin(ywmbessie@yeah.net) ; Zuo, Zhili(zuozhili@mail.kib.ac.cn)
英文摘要	Adenylyl cyclases (ACs), which are responsible for catalyzing the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP), play a critical role in cell signal transduction. In this study, a combined approach involving docking-based virtual screening, with the combination of homology modeling followed by an in-vitro, and cell-based biological assay have been performed for discovering a class of novel potent and selective isoform adenylyl cyclase type 8 (AC8) agonist. The computer-aided virtual screening was used to identify fourteen virtual cluster compounds as potential hits which were further subjected to rigorous bioassays. A novel hit compound VHC-7 (ethyl 3-(2,4-dichlorobenzyl)-2-oxoindoline-3-carboxylate) was identified as a highly potent selective AC8 agonist with EC50 value of 0.1052 +/- 0.038 mu M. Remarkably, the molecule herein reported can be explored further to discover greater number of hit compounds with better pharmacokinetic properties as well as to serve as a promising novel hit agonist of AC8 for the treatment of various central nervous system disorders and its associated diseases.
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
WOS记录号	WOS:000504873300015
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/70523]
专题	昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Yang, Weimin; Zuo, Zhili
作者单位	1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Kunming Med Univ, Dept Resp Med, Affiliated Hosp 2, Kunming 650031, Yunnan, Peoples R China 3.Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China 4.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Weng, Zhiying,Xu, Guowei,Chen, Dingyuan,et al. Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2020,30(2):7.
APA	Weng, Zhiying.,Xu, Guowei.,Chen, Dingyuan.,Yang, Yaqing.,Song, Gao.,...&Zuo, Zhili.(2020).Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,30(2),7.
MLA	Weng, Zhiying,et al."Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 30.2(2020):7.