5V4W

Human glucokinase in complex with novel indazole activator.

5V4W の概要

• エントリーDOI: 10.2210/pdb5v4w/pdb
• 関連するPDBエントリー: 5V4X
• 分子名称: Glucokinase, alpha-D-glucopyranose, (2S)-2-[4-(cyclopropylsulfonyl)-1H-indazol-1-yl]-N-(5-fluoro-1,3-thiazol-2-yl)-3-(oxan-4-yl)propanamide, ... (5 entities in total)
• 機能のキーワード: activator, complex, allosteric, transferase-transferase activator complex, transferase/transferase activator
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52160.95

構造登録者

Skene, R.J.,Hosfield, D.J. (登録日: 2017-03-10, 公開日: 2017-05-31, 最終更新日: 2024-03-06)

主引用文献

Cheruvallath, Z.S.,Gwaltney, S.L.,Sabat, M.,Tang, M.,Wang, H.,Jennings, A.,Hosfield, D.,Lee, B.,Wu, Y.,Halkowycz, P.,Grimshaw, C.E.
Discovery of potent and orally active 1,4-disubstituted indazoles as novel allosteric glucokinase activators.
Bioorg. Med. Chem. Lett., 27:2678-2682, 2017

PubMed Abstract: Guided by co-crystal structural information obtained from a different series we were exploring, a scaffold morphing and SBDD approach led to the discovery of the 1,4-disubstituted indazole series as a novel class of GKAs that potently activate GK in enzyme and cell assays. anti-diabetic OGTT efficacy was demonstrated with 29 in a rodent models of type 2 diabetes.

PubMed: 28512030
DOI: 10.1016/j.bmcl.2017.04.041

実験手法

X-RAY DIFFRACTION (2.39 Å)