Open AccessDiscovery of a first-in-class inhibitor of sulfide:quinone oxidoreductase that protects against adverse cardiac remodelling and heart failure
Author(s) -
Michael R. Jackson,
Kristie Dawn Cox,
Simon D. P. Baugh,
Luke Wakeen,
Adel A. Rashad,
Patrick Y.S. Lam,
Boris Polyak,
Marilyn Schuman Jörns
Publication year - 2021
Publication title -
cardiovascular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.774
H-Index - 219
eISSN - 1755-3245
pISSN - 0008-6363
DOI - 10.1093/cvr/cvab206
Subject(s) - heart failure , pharmacology , chemistry , medicine , biochemistry , cancer research
Hydrogen sulfide (H2S) is a potent signalling molecule that activates diverse cardioprotective pathways by post-translational modification (persulfidation) of cysteine residues in upstream protein targets. Heart failure patients with reduced ejection fraction (HFrEF) exhibit low levels of H2S. Sulfide:quinone oxidoreductase (SQOR) catalyses the first irreversible step in the metabolism of H2S and plays a key role in regulating H2S-mediated signalling. Here, the aim of this study was to discover a first-in-class inhibitor of human SQOR and evaluate its cardioprotective effect in an animal model of HFrEF.