4hgl
From Proteopedia
Crystal structure of ck1g3 with compound 1
Structural highlights
Function[KC1G3_HUMAN] Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate (By similarity). Publication Abstract from PubMedAberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1gamma 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 CK1gamma 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. Structure-Based Design of Potent and Selective CK1gamma Inhibitors.,Huang H, Acquaviva L, Berry V, Bregman H, Chakka N, O'Connor A, DiMauro EF, Dovey J, Epstein O, Grubinska B, Goldstein J, Gunaydin H, Hua Z, Huang X, Huang L, Human J, Long A, Newcomb J, Patel VF, Saffran D, Serafino R, Schneider S, Strathdee C, Tang J, Turci S, White R, Yu V, Zhao H, Wilson C, Martin MW ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64. doi: 10.1021/ml300278f. eCollection, 2012 Dec 13. PMID:24900428[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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