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

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

  • J Med Chem. 2019 Feb 14;62(3):1677-1683. doi: 10.1021/acs.jmedchem.8b01720.
Youtian Hu 1,  Lu Wang 2,  Xu Han 3,  Yueyang Zhou 1,  Tonghui Zhang 1,  Li Wang 1,  Ting Hong 1 4,  Wei Zhang 5,  Xun-Xiang Guo 1,  Jielin Sun 1,  Yingxin Qi 2,  Jing Yu 5,  Hong Liu 3,  Fang Wu 1
Affiliations

Affiliations

  • 1 Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine , Shanghai Jiao Tong University , Shanghai 200240 , China.
  • 2 Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology , Shanghai Jiao Tong University , Shanghai 200240 , China.
  • 3 State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 , China.
  • 4 Science and Technology College , Jiangxi University of Traditional Chinese Medicine , Nanchang 330004 , China.
  • 5 State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences & Biotechnology , Shanghai Jiao Tong University , Shanghai 200240 , China.
PMID: 30562026 DOI: 10.1021/acs.jmedchem.8b01720
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 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.

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