Discovery of potent and selective CDK8 inhibitors through FBDD approach.

ID: ALA4043169

Journal: Bioorg Med Chem Lett

Title: Discovery of potent and selective CDK8 inhibitors through FBDD approach.

Authors: Han X, Jiang M, Zhou C, Zhou Z, Xu Z, Wang L, Mayweg AV, Niu R, Jin TG, Yang S.

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. Compound 16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability.

CiteXplore: 28802632

DOI: 10.1016/j.bmcl.2017.07.080

Patent ID: ┄