5XS2

CDK8-CYCC IN COMPLEX WITH COMPOUND 17:3-chloro-4-(4-pyridyl)-1H-pyrrole-2-carboxamide

Summary for 5XS2

• Entry DOI: 10.2210/pdb5xs2/pdb
• Descriptor: Cyclin-dependent kinase 8, Cyclin-C, GLYCEROL, ... (5 entities in total)
• Functional Keywords: cdk8, cyclin c, mediator complex, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P49336 P24863
• Total number of polymer chains: 2
• Total formula weight: 75796.50

Authors

Zhou, Z.,Xu, Z. (deposition date: 2017-06-12, release date: 2017-08-09, Last modification date: 2024-03-27)

Primary citation

Han, X.,Jiang, M.,Zhou, C.,Zhou, Z.,Xu, Z.,Wang, L.,Mayweg, A.V.,Niu, R.,Jin, T.G.,Yang, S.
Discovery of potent and selective CDK8 inhibitors through FBDD approach
Bioorg. Med. Chem. Lett., 27:4488-4492, 2017

PubMed 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.

PubMed: 28802632
DOI: 10.1016/j.bmcl.2017.07.080

Experimental method

X-RAY DIFFRACTION (2.04 Å)