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ID: ALA4673222

Journal: J Med Chem

Title: Discovery of a Bioactive Inhibitor with a New Scaffold for Cystathionine γ-Lyase.

Authors: Hu Y,Wang L,Han X,Zhou Y,Zhang T,Wang L,Hong T,Zhang W,Guo XX,Sun J,Qi Y,Yu J,Liu H,Wu F

Abstract: We identify three submicromolar inhibitors with new chemical scaffolds for cystathionine γ-lyase (CSE) by a tandem-well-based high-throughput assay. NSC4056, the most potent inhibitor with an IC of 0.6 μM, which is also known as aurintricarboxylic acid, selectively binds to Arg and Tyr residues of CSE active site and preferably inhibits the CSE activity in cells rather than cystathionine β-synthase (CBS), the other HS-generating enzyme. Moreover, NSC4056 effectively rescues hypotension in hemorrhagic shock rats.

CiteXplore: 30562026

DOI: 10.1021/acs.jmedchem.8b01720