| Literature DB >> 27391855 |
Kay Ahn1,2, Markus Boehm1,2, Matthew F Brown1,2, Jessica Calloway1,2, Ye Che1,2, Jinshan Chen1,2, Kimberly F Fennell1,2, Kieran F Geoghegan1,2, Adam M Gilbert1,2, Jemy A Gutierrez1,2, Amit S Kalgutkar1,2, Adhiraj Lanba1,2, Chris Limberakis1,2, Thomas V Magee1,2, Inish O'Doherty1,2, Robert Oliver1,2, Brandon Pabst1,2, Jayvardhan Pandit1,2, Kevin Parris1,2, Jeffrey A Pfefferkorn1,2, Timothy P Rolph1,2, Rushi Patel1,2, Brandon Schuff1,2, Veerabahu Shanmugasundaram1,2, Jeremy T Starr1,2, Alison H Varghese1,2, Nicholas B Vera1,2, Cecile Vernochet1,2, Jiangli Yan1,2.
Abstract
Lysophospholipase-like 1 (LYPLAL1) is an uncharacterized metabolic serine hydrolase. Human genome-wide association studies link variants of the gene encoding this enzyme to fat distribution, waist-to-hip ratio, and nonalcoholic fatty liver disease. We describe the discovery of potent and selective covalent small-molecule inhibitors of LYPLAL1 and their use to investigate its role in hepatic metabolism. In hepatocytes, selective inhibition of LYPLAL1 increased glucose production supporting the inference that LYPLAL1 is a significant actor in hepatic metabolism. The results provide an example of how a selective chemical tool can contribute to evaluating a hypothetical target for therapeutic intervention, even in the absence of complete biochemical characterization.Entities:
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Year: 2016 PMID： 27391855 DOI： 10.1021/acschembio.6b00266
Source DB: PubMed Journal: ACS Chem Biol ISSN： 1554-8929 Impact factor: 5.100