7EZF

Indole-2-carboxylic acid derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase

7EZF の概要

• エントリーDOI: 10.2210/pdb7ezf/pdb
• 分子名称: Fructose-1,6-bisphosphatase 1, 7-chloranyl-5-ethyl-3-(3-hydroxy-3-oxopropyl)-1H-indole-2-carboxylic acid, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (4 entities in total)
• 機能のキーワード: fructose-1, 6-bisphosphatase, indole dicarboxylic acid derivative inhibitor, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 150093.07

構造登録者

Wang, X.Y.,Zhou, J.,Xu, B.L. (登録日: 2021-06-01, 公開日: 2022-06-01, 最終更新日: 2023-11-29)

主引用文献

Wang, X.,Zhao, R.,Ji, W.,Zhou, J.,Liu, Q.,Zhao, L.,Shen, Z.,Liu, S.,Xu, B.
Discovery of Novel Indole Derivatives as Fructose-1,6-bisphosphatase Inhibitors and X-ray Cocrystal Structures Analysis.
Acs Med.Chem.Lett., 13:118-127, 2022

PubMed Abstract: Liver fructose-1,6-bisphosphatase (FBPase) is a key enzyme in the gluconeogenesis, and its inhibitors are expected to be novel antidiabetic agents. Herein, a series of new indole and benzofuran analogues were designed and synthesized to evaluate the inhibitory activity against FBPase. As a result, the novel FBPase inhibitors bearing -acylsulfonamide moiety on the 3-position of the indole-2-carboxylic acid scaffold (compounds and ) were identified with ICs at the submicromolar levels. Three X-ray crystal structures of the complexes were solved and revealed the structural basis for the inhibitory activity. The chemoinformatics analysis further disclosed the distinct binding features of this class of inhibitors, providing an insight for further modifications to create structurally distinct FBPase inhibitors with high potency and drug-like properties.

PubMed: 35059131
DOI: 10.1021/acsmedchemlett.1c00613

実験手法

X-RAY DIFFRACTION (2.76 Å)