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

doi:10.1016/j.bmcl.2019.126823

	Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening
	Weng, Zhiying 1,2; Xu, Guowei 3; Chen, Dingyuan3 ; Yang, Yaqing 1,2; Song, Gao 1,2; Shen, Wen 4; Zhang, Shuqun 3; Wang, LiangLiang 3; Yang, Weimin 1,2; Zuo, Zhili3
通讯作者	Yang, Weimin(ywmbessie@yeah.net) ; Zuo, Zhili(zuozhili@mail.kib.ac.cn)
	2020-01-15
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN	0960-894X
卷号	30 期号:2 页码:7
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.
关键词	Adenylyl cyclases Homology modeling Consensus scoring Molecular dynamics simulation Virtual screening Biological evaluation
DOI	10.1016/j.bmcl.2019.126823
收录类别	SCI ; SCI
语种	英语
WOS记录号	WOS:000504873300015
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/70524
专题	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.Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China 2.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Yunnan, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 4.Kunming Med Univ, Dept Resp Med, Affiliated Hosp 2, Kunming 650031, 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.