ArticleInternational journal of molecular sciences2025
The Selective 3-MST Inhibitor I3MT-3 Works as a Potent Caspase-1 Inhibitor.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Hydrogen sulfide regulation in redox homeostasis and programmed cell death: mechanistic insights and implications in cancer.Journal of advanced research · 2026Review
- Identification of potential inhibitors of 3‑mercaptopyruvate sulfurtransferase with a deep-learning based screening of natural products.Journal of computer-aided molecular design · 2026Article
- Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors.Frontiers in physiology · 2026Review
- AMPK Limits MNNG-Induced Parthanatos by Inhibiting BH3-Only Protein Bim.International journal of molecular sciences · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
I3MT-3 (HMPSNE) has been identified as a selective inhibitor of the supersulfide-producing enzyme 3-MST. In this study, we found that I3MT-3 inhibits inflammatory responses, including the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) and inflammatory cell death pyroptosis, induced by the activation of the inflammasomes composed of NLRP1, NLRP3, or AIM2. However, interestingly, the knockdown of 3-MST did not affect the activation of the inflammasomes, suggesting that the inhibitory effect of I3MT-3 on inflammasome activation is mediated by alternative ways rather than the inhibition of 3-MST. Interestingly, an in vitro caspase assay revealed that I3MT-3 directly inhibits caspase-1 activation, and molecular docking simulations raised the possibility that the pyrimidone ring in I3MT-3 stabilizes direct interaction of I3MT-3 with caspase-1. Taken together, our data suggest that I3MT-3 inhibits inflammasome activation by targeting caspase-1, and show I3MT-3 as a potent inhibitor of caspase-1.
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