Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening
Weng, Zhiying1,2; Xu, Guowei3; Chen, Dingyuan3; Yang, Yaqing1,2; Song, Gao1,2; Shen, Wen4; Zhang, Shuqun3; Wang, LiangLiang3; Yang, Weimin1,2; Zuo, Zhili3
Corresponding AuthorYang, Weimin(ywmbessie@yeah.net) ; Zuo, Zhili(zuozhili@mail.kib.ac.cn)
2020-01-15
Source PublicationBIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN0960-894X
Volume30Issue:2Pages:7
AbstractAdenylyl 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.
KeywordAdenylyl cyclases Homology modeling Consensus scoring Molecular dynamics simulation Virtual screening Biological evaluation
DOI10.1016/j.bmcl.2019.126823
Indexed BySCI ; SCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Chemistry
WOS SubjectChemistry, Medicinal ; Chemistry, Organic
WOS IDWOS:000504873300015
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/70524
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorYang, Weimin; Zuo, Zhili
Affiliation1.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
Recommended Citation
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.
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