9fhe

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

spinqualitylabelsall models 9fhe, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9fhe is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.313Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease KHK_HUMAN Defects in KHK are the cause of fructosuria (FRUCT) [MIM:229800. Benign defect of intermediary metabolism. Function KHK_HUMAN Publication Abstract from PubMed 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. Discovery of BI-9787, a potent zwitterionic ketohexokinase inhibitor with oral bioavailability.,Heine N, Weber A, Pautsch A, Gottschling D, Uphues I, Bauer M, Ebenhoch R, Magarkar A, Nosse B, Kley JT Bioorg Med Chem Lett. 2024 Aug 22;112:129930. doi: 10.1016/j.bmcl.2024.129930. PMID:39179180 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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