ArticleNature immunology2025
Delaying pyroptosis with an AI-screened gasdermin D pore blocker mitigates inflammatory response.
Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Exercise-Induced Exerkines: Multi-Nodal Suppression of the NLRP3 Inflammasome and Translational Potential.Medicinal research reviews · 2026Review
- High-throughput screening identifies FDA approved drug mitiglinide as a novel pyroptosis inhibitor and therapeutic agent for osteoarthritis.Journal of advanced research · 2026Article
- Intensification versus combination: revisiting the past and envisioning the future of LDHA inhibitors.Cancer chemotherapy and pharmacology · 2026Review
- Staphylococcus aureus-vascular endothelium interactions: Mechanisms and therapeutic opportunities.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- PAD4-generated citrullinated histones are triggers for autoinflammation in cryopyrin-associated periodic syndrome.Cell death and differentiation · 2026Article
- The Co-Evolutionary Arms Race BetweenMicroorganisms · 2026Review
- Folate-mediated inflammatory microenvironment-responsive nanocarriers for the delivery of Moringa A to target NLRP3 for the treatment of viral pneumonia.International journal of pharmaceutics: X · 2026Article
- Deep Learning for Anticancer Drug Discovery Targeting Non-Apoptotic Regulated Cell Death Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Endoplasmic Reticulum-Targeting NIR Cyanine ER800 Nanoparticles Promote Pyroptosis in Triple-Negative Breast Cancer.ACS applied materials & interfaces · 2026Article
- Hypothalamic regulation of sepsis-associated anorexia: cytokine and hormonal signalling through AgRP/POMC circuits.EMBO molecular medicine · 2026Review
- Cross-Talk Between Pyroptosis and Ferroptosis Promotes Intestinal Inflammation and Barrier Failure During PEDV Infection.Biomolecules · 2026Article
- Self-amplifying RNA therapy encoding CNTF with disulfiram co-delivery promotes optic nerve repair through microglial pyroptosis inhibition and RGC axonal regeneration.Journal of nanobiotechnology · 2026Article
- Artificial intelligence-driven peptide blocks gasdermin pyroptosis and alleviates inflammation.Precision clinical medicine · 2026Article
- "Zombie virus" like pyroptosis: Extracellular vesicles spread pyroptosis by transferring functional N-GSDMD pore.Journal of translational internal medicine · 2026Article
- Inflammasome-associated pyroptosis and tumor angiogenesis in prostate cancer.Iranian journal of basic medical sciences · 2026Review
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- The Role of Pyroptosis in Exacerbating Sepsis-Induced Myocardial Injury: Mechanisms and Implications.Journal of inflammation research · 2026Review
- Multifaceted mechanisms of unconventional T cells in ischemia-reperfusion injury.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
The formation of membrane pores by cleaved N-terminal gasdermin D (GSDMD-NT) results in the release of cytokines and inflammatory cell death, known as pyroptosis. Blocking GSDMD-NT pores is an attractive and promising strategy for mitigating inflammation. Here we demonstrate that SK56, an artificial intelligence-screened peptide, effectively obstructs GSDMD-NT pores and inhibits pyroptosis and cytokine release in macrophages and human peripheral blood leukocyte-induced pyroptosis. SK56 prevents septic death induced by lipopolysaccharide or cecal ligation and puncture surgery in mice. SK56 does not influence cleavage of interleukin-1β or GSDMD. Instead, SK56 inhibits the release of cytokines from pyroptotic macrophages, mitigates the activation of primary mouse dendritic cells triggered by incubation with pyroptotic cytomembranes and prevents widespread cell death of human alveolar organoids in an organoid-macrophage coculture model. SK56 blocks GSDMD-NT pores on lipid-bilayer nanoparticles and enters pyroptotic macrophages to inhibit mitochondrial damage. SK56 presents new therapeutic possibilities for counteracting inflammation, which is implicated in numerous diseases.
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