2. Academic Validation
  3. Discovery of potent and selective CDK8 inhibitors through FBDD approach

Discovery of potent and selective CDK8 inhibitors through FBDD approach

  • Bioorg Med Chem Lett. 2017 Sep 15;27(18):4488-4492. doi: 10.1016/j.bmcl.2017.07.080.
Xingchun Han 1,  Min Jiang 2,  Chengang Zhou 2,  Zheng Zhou 3,  Zhiheng Xu 3,  Lisha Wang 3,  Alexander V Mayweg 2,  Rui Niu 4,  Tai-Guang Jin 4,  Song Yang 5
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Roche Innovation Center Shanghai, Bldg 5, 720 Cailun Road, Shanghai 201203, China. Electronic address: [email protected].
  • 2 Medicinal Chemistry, Roche Innovation Center Shanghai, Bldg 5, 720 Cailun Road, Shanghai 201203, China.
  • 3 Chemical Biology, Roche Innovation Center Shanghai, Bldg 5, 720 Cailun Road, Shanghai 201203, China.
  • 4 Discovery Oncology, Roche Innovation Center Shanghai, Bldg 5, 720 Cailun Road, Shanghai 201203, China.
  • 5 Medicinal Chemistry, Roche Innovation Center Shanghai, Bldg 5, 720 Cailun Road, Shanghai 201203, China. Electronic address: [email protected].
PMID: 28802632 DOI: 10.1016/j.bmcl.2017.07.080
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.

Keywords

CDK8; Fragment-based drug discovery (FBDD); Inhibitor.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-103492
    99.77%, CDK Inhibitor
    CDK