View source for 9fhe


==hKHK-C in complex with BI-9787 (pH 5.5)==
<StructureSection load='9fhe' size='340' side='right'caption='[[9fhe]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fhe]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FHE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.313&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9fhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fhe OCA], [https://pdbe.org/9fhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fhe RCSB], [https://www.ebi.ac.uk/pdbsum/9fhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fhe ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN] Defects in KHK are the cause of fructosuria (FRUCT) [MIM:[https://omim.org/entry/229800 229800]. Benign defect of intermediary metabolism.<ref>PMID:19237742</ref> <ref>PMID:7833921</ref> 
== Function ==
[https://www.uniprot.org/uniprot/KHK_HUMAN KHK_HUMAN] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:39179180</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fhe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ebenhoch R]]
[[Category: Pautsch A]]