4HGL

Crystal structure of ck1g3 with compound 1

4HGL の概要

• エントリーDOI: 10.2210/pdb4hgl/pdb
• 関連するPDBエントリー: 4G16 4G17 4HGS 4HGT
• 分子名称: 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)
• 機能のキーワード: ck1g, kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9Y6M4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38936.68

構造登録者

Huang, X. (登録日: 2012-10-08, 公開日: 2012-11-21, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)