Summary for 9FHD
| Entry DOI | 10.2210/pdb9fhd/pdb |
| Descriptor | Ketohexokinase, SULFATE ION, (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, ... (4 entities in total) |
| Functional Keywords | kinase, sugar kinase, ketohexokinase, fructokinase, co-structure, sugar binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 69420.52 |
| Authors | |
| Primary citation | 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 Cited by 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: 39179180DOI: 10.1016/j.bmcl.2024.129930 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.845 Å) |
Structure validation
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