5F94

Crystal structure of GSK3b in complex with Compound 15: 2-[(cyclopropylcarbonyl)amino]-N-(4-methoxypyridin-3-yl)pyridine-4-carboxamide

5F94 の概要

• エントリーDOI: 10.2210/pdb5f94/pdb
• 関連するPDBエントリー: 5F95
• 分子名称: Glycogen synthase kinase-3 beta, 2-[(cyclopropylcarbonyl)amino]-N-(4-methoxypyridin-3-yl)pyridine-4-carboxamide (3 entities in total)
• 機能のキーワード: gsk3b, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P49841
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80312.34

構造登録者

Lewis, H.A.,Kish, K.,Luo, G.,Dubowchick, G.M. (登録日: 2015-12-09, 公開日: 2016-02-03, 最終更新日: 2024-03-06)

主引用文献

Luo, G.,Chen, L.,Burton, C.R.,Xiao, H.,Sivaprakasam, P.,Krause, C.M.,Cao, Y.,Liu, N.,Lippy, J.,Clarke, W.J.,Snow, K.,Raybon, J.,Arora, V.,Pokross, M.,Kish, K.,Lewis, H.A.,Langley, D.R.,Macor, J.E.,Dubowchik, G.M.
Discovery of Isonicotinamides as Highly Selective, Brain Penetrable, and Orally Active Glycogen Synthase Kinase-3 Inhibitors.
J.Med.Chem., 59:1041-1051, 2016

PubMed Abstract: GSK-3 is a serine/threonine kinase that has numerous substrates. Many of these proteins are involved in the regulation of diverse cellular functions, including metabolism, differentiation, proliferation, and apoptosis. Inhibition of GSK-3 may be useful in treating a number of diseases including Alzheimer's disease (AD), type II diabetes, mood disorders, and some cancers, but the approach poses significant challenges. Here, we present a class of isonicotinamides that are potent, highly kinase-selective GSK-3 inhibitors, the members of which demonstrated oral activity in a triple-transgenic mouse model of AD. The remarkably high kinase selectivity and straightforward synthesis of these compounds bode well for their further exploration as tool compounds and therapeutics.

PubMed: 26751161
DOI: 10.1021/acs.jmedchem.5b01550

実験手法

X-RAY DIFFRACTION (2.51 Å)