ArticleCardiovascular research2022
Discovery of a first-in-class inhibitor of sulfide:quinone oxidoreductase that protects against adverse cardiac remodelling and heart failure.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- The Orally Available Ghrelin Receptor-Agonist AC01 Improves Systolic Function in HFrEF Mice and Nonhuman Primates.JACC. Basic to translational science · 2026Article
- Unraveling competitive protein interactions: A critical step toward improved production and therapeutics.Journal of advanced research · 2026Review
- CoQExperimental & molecular medicine · 2026Review
- Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors.Frontiers in physiology · 2026Review
- Hydrogen Sulfide Consumption and Cell Bioenergetics in Human (Patho)physiology.Handbook of experimental pharmacology · 2026Review
- Manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) represses sulfide:quinone oxidoreductase expression and targets the sulfido-redox system in glioblastoma models.Redox report : communications in free radical research · 2025Article
- The potential role of hydrogen sulfide-autophagy axis in diseases.Journal of physiology and biochemistry · 2025Review
- Cardiac fibrosis: from mechanisms and models to medicines.Trends in pharmacological sciences · 2025Review
- Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism.JACC. Basic to translational science · 2025Article
- Hydrogen sulfide/polysulfides signaling and neuronal diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Review
- Knockout of the sulfide: quinone oxidoreductase SQR reduces growth of HCT116 tumor xenograft.Redox biology · 2025Article
- Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025Review
- QRICH1 regulates ATF6 transcription to affect pathological cardiac hypertrophy progression.Molecular medicine (Cambridge, Mass.) · 2025Article
- SQOR as a metabolic rheostat of HFrontiers in cell and developmental biology · 2025Review
- Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Dapagliflozin protects against chronic heart failure in mice by inhibiting macrophage-mediated inflammation, independent of SGLT2.Cell reports. Medicine · 2023Article
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights.Molecules (Basel, Switzerland) · 2023Article
- Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies.Redox biology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aimsHydrogen 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. METHODS AND
resultsWe identified a potent inhibitor of human SQOR (STI1, IC50 = 29 nM) by high-throughput screening of a small-molecule library, followed by focused medicinal chemistry optimization and structure-based design. STI1 is a competitive inhibitor that binds with high selectivity to the coenzyme Q-binding pocket in SQOR. STI1 exhibited very low cytotoxicity and attenuated the hypertrophic response of neonatal rat ventricular cardiomyocytes and H9c2 cells induced by neurohormonal stressors. A mouse HFrEF model was produced by transverse aortic constriction (TAC). Treatment of TAC mice with STI1 mitigated the development of cardiomegaly, pulmonary congestion, dilatation of the left ventricle, and cardiac fibrosis and decreased the pressure gradient across the aortic constriction. Moreover, STI1 dramatically improved survival, preserved cardiac function, and prevented the progression to HFrEF by impeding the transition from compensated to decompensated left ventricle hypertrophy.
conclusionWe demonstrate that the coenzyme Q-binding pocket in human SQOR is a druggable target and establish proof of concept for the potential of SQOR inhibitors to provide a novel therapeutic approach for the treatment of HFrEF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.