ArticleBasic research in cardiology2023
Novel GSDMD inhibitor GI-Y1 protects heart against pyroptosis and ischemia/reperfusion injury by blocking pyroptotic pore formation.
Article in Basic research in cardiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.Neurotoxicity research · 2026Review
- Dihydromyricetin Ameliorates Myocardial Ischemia-Reperfusion Injury by Modulating CKLF1-Mediated Cardiomyocyte Pyroptosis.Phytotherapy research : PTR · 2026Article
- Gasdermin D in Neurodegenerative Diseases: Pathogenic Roles and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Cardiomyocyte-derived GPX4 stabilizes BNIP3 to facilitate mitophagy and mitigate myocardial ischemia/reperfusion injury.Nature communications · 2026Article
- Cardiomyocyte-Derived USP20 Attenuates Diabetic Cardiomyopathy by Facilitating the Degradation of STING and Mitigating STING-Mediated Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Macrophage pyroptosis inhibition alleviates postinjury neointimal formation and vascular restenosis.Journal of translational medicine · 2026Article
- Cell death forms in myocardial ischemia-reperfusion injury and their potential clinical applications.Molecular and cellular biochemistry · 2026Review
- De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell death mechanisms in heat stroke and sepsis: ZBP1 and caspase-11 as molecular sensors driving the MLKL/GSDMD death execution axis.Frontiers in cell and developmental biology · 2026Review
- Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.Mediators of inflammation · 2026Review
- Repurposing disulfiram: targeting Zeb1 to attenuate paraquat-induced pulmonary fibrosis in rats.Journal of molecular histology · 2025Article
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Different types of cell death and their interactions in myocardial ischemia-reperfusion injury.Cell death discovery · 2025Review
- The novel GSDMD inhibitor GI-Y2 exerts antipyroptotic effects to reduce atherosclerosis.Clinical and translational medicine · 2025Article
- GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Ubiquitin-specific protease 25 improves myocardial ischemia-reperfusion injury by deubiquitinating NLRP3 and negatively regulating NLRP3 inflammasome activity in cardiomyocytes.Clinical and translational medicine · 2025Article
- Therapeutic Potential of Gasdermin D-Mediated Myocardial Pyroptosis in Ischaemic Heart Disease: Expanding the Paradigm From Bench to Clinical Insights.Journal of cellular and molecular medicine · 2025Review
- Quercetin in Shengxian Decoction exhibits anti-ferroptosis protective roles in a myocardial infarction modelFrontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of gasdermin D (GSDMD) and its concomitant cardiomyocyte pyroptosis are critically involved in multiple cardiac pathological conditions. Pharmacological inhibition or gene knockout of GSDMD could protect cardiomyocyte from pyroptosis and dysfunction. Thus, seeking and developing highly potent GSDMD inhibitors probably provide an attractive strategy for treating diseases targeting GSDMD. Through structure-based virtual screening, pharmacological screening and subsequent pharmacological validations, we preliminarily identified GSDMD inhibitor Y1 (GI-Y1) as a selective GSDMD inhibitor with cardioprotective effects. Mechanistically, GI-Y1 binds to GSDMD and inhibits lipid- binding and pyroptotic pore formation of GSDMD-N by targeting the Arg7 residue. Importantly, we confirmed the cardioprotective effect of GI-Y1 on myocardial I/R injury and cardiac remodeling by targeting GSDMD. More extensively, GI-Y1 also inhibited the mitochondrial binding of GSDMD-N and its concomitant mitochondrial dysfunction. The findings of this study identified a new drug (GI-Y1) for the treatment of cardiac disorders by targeting GSDMD, and provide a new tool compound for pyroptosis research.
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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.