Discovery of potent and selective CDK8 inhibitors through FBDD approach. Issue 18 (15th September 2017)

• Record Type: Journal Article
• Authors: Han, Xingchun; Jiang, Min; Zhou, Chengang; Zhou, Zheng; Xu, Zhiheng; Wang, Lisha; Mayweg, Alexander V.; Niu, Rui; Jin, Tai-Guang; Yang, Song
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 18(2017)
• Page Start: 4488
• Page End: 4492
• Publication Date: 2017-09-15
• Subjects: CDK8 -- Inhibitor -- Fragment-based drug discovery (FBDD); Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.080
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors. Optimization of a fragment hit guided by co-crystal structures led to identification of a novel series of potent CDK8 inhibitors which are highly ligand efficient, kinase selective and cellular active. Compound16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability.