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Discovery of a Bioactive Inhibitor with a New Scaffold for Cystathionine γ‑Lyase

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posted on 18.12.2018, 00:00 by Youtian Hu, Lu Wang, Xu Han, Yueyang Zhou, Tonghui Zhang, Li Wang, Ting Hong, Wei Zhang, Xun-Xiang Guo, Jielin Sun, Yingxin Qi, Jing Yu, Hong Liu, Fang Wu
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 IC50 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 H2S-generating enzyme. Moreover, NSC4056 effectively rescues hypotension in hemorrhagic shock rats.