9FHE

hKHK-C in complex with BI-9787 (pH 5.5)

これはPDB形式変換不可エントリーです。

9FHE の概要

• エントリーDOI: 10.2210/pdb9fhe/pdb
• 分子名称: Ketohexokinase, (2~{S})-3-[3-[[4-[bis(fluoranyl)methyl]-3-cyano-6-[(3~{S})-3-(dimethylamino)pyrrolidin-1-yl]pyridin-2-yl]amino]-4-methylsulfanyl-phenyl]-2-methyl-propanoic acid (3 entities in total)
• 機能のキーワード: kinase, sugar kinase, ketohexokinase, fructokinase, co-structure, sugar binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69132.33

構造登録者

Ebenhoch, R.,Pautsch, A. (登録日: 2024-05-27, 公開日: 2024-09-04)

主引用文献

Heine, N.,Weber, A.,Pautsch, A.,Gottschling, D.,Uphues, I.,Bauer, M.,Ebenhoch, R.,Magarkar, A.,Nosse, B.,Kley, J.T.
Discovery of BI-9787, a potent zwitterionic ketohexokinase inhibitor with oral bioavailability.
Bioorg.Med.Chem.Lett., 112:129930-129930, 2024

PubMed Abstract: Fructose metabolism by ketohexokinase (KHK) is implicated in a variety of metabolic disorders. KHK inhibition is a potential therapeutic strategy for the treatment of diseases including diabetes, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis. The first small-molecule KHK-inhibitors have entered clinical trials, but it remains unclear if systemic inhibition of KHK by small-molecules will eventually benefit patients. Here we report the discovery of BI-9787, a potent, zwitterionic KHK inhibitor characterized by high permeability and favorable oral rat pharmacokinetics. BI-9787 was identified by optimizing chemical starting points generated via a ligand-based virtual screening of Boehringer's virtual library of synthetically accessible compounds (BICLAIM). It serves as a high-quality in vitro and in vivo tool compound for investigating the role of fructose metabolism in disease.

PubMed: 39179180
DOI: 10.1016/j.bmcl.2024.129930

実験手法

X-RAY DIFFRACTION (2.313 Å)