4HGL

Crystal structure of ck1g3 with compound 1

Summary for 4HGL

• Entry DOI: 10.2210/pdb4hgl/pdb
• Related: 4G16 4G17 4HGS 4HGT
• Descriptor: Casein kinase I isoform gamma-3, 2-[5-methoxy-2-(quinolin-3-yl)pyrimidin-4-yl]-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one, SULFATE ION, ... (4 entities in total)
• Functional Keywords: ck1g, kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9Y6M4
• Total number of polymer chains: 1
• Total formula weight: 38936.68

Authors

Huang, X. (deposition date: 2012-10-08, release date: 2012-11-21, Last modification date: 2024-02-28)

Primary citation

Huang, H.,Acquaviva, L.,Berry, V.,Bregman, H.,Chakka, N.,O'Connor, A.,DiMauro, E.F.,Dovey, J.,Epstein, O.,Grubinska, B.,Goldstein, J.,Gunaydin, H.,Hua, Z.,Huang, X.,Huang, L.,Human, J.,Long, A.,Newcomb, J.,Patel, V.F.,Saffran, D.,Serafino, R.,Schneider, S.,Strathdee, C.,Tang, J.,Turci, S.,White, R.,Yu, V.,Zhao, H.,Wilson, C.,Martin, M.W.
Structure-Based Design of Potent and Selective CK1 gamma Inhibitors.
ACS Med Chem Lett, 3:1059-1064, 2012

PubMed Abstract: Aberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1γ in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We describe a structure-based approach that led to the discovery of a series of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors. These compounds exhibited good enzyme and cell potency, as well as selectivity against other CK1 isoforms. A single oral dose of compound 13 resulted in significant inhibition of LRP6 phosphorylation in a mouse tumor PD model.

PubMed: 24900428
DOI: 10.1021/ml300278f

Experimental method

X-RAY DIFFRACTION (2.4 Å)