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Review Article

Drugging the Inflammasome Gasdermin Axis: Toward Precision Control of Pyroptosis

Authors

  • Deborah Pelumi Fadipe Cell Biology, Illinois Institute of Technology, Chicago, Illinois, USA

    deborahfadipe90@gmail.com

  • Oluwapelumi Hannah Sonoiki Department of Biology, Eastern Washington University, Cheney, Washington, USA
  • Emmanuel Aanu Bankole Department of Mechanical, Aerospace and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA https://orcid.org/0009-0006-7897-7032
  • Loveth Chinwendu Iwuala Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA
  • Shalom Jesufunminiye Adedeji Isolo General Hospital, Isolo, Lagos State, Nigeria
  • Chinedu George Ezeah Department of Pharmaceutical Chemistry, University of Nigeria, Nsukka, Nigeria
  • Reginald Oyortey Department of Pharmaceutical Science, Central University, Ghana https://orcid.org/0009-0006-7212-117X

Abstract

Pyroptosis, an inflammasome-driven, gasdermin-mediated form of lytic cell death, has emerged as a unifying mechanism in disorders ranging from sepsis to Alzheimer’s disease. Canonical and non-canonical pathways converge on caspase-1/4/5/11 cleavage of gasdermin D, releasing IL-1β and IL-18; basal epithelial IL-18 preserves barrier integrity, whereas unchecked cytokine efflux fuels cardiovascular, metabolic, and neuro-inflammation. Early translational successes include the oral NLRP3 inhibitor dapansutrile, which lowered synovial IL-1β by 72 % and halved pain scores in a phase II gout-flare trial, and tadekinig alfa, a recombinant IL-18-binding protein now in phase II for NLRC4-MAS. Repurposed disulfiram blocks gasdermin pores pre-clinically, while AI-guided structure screens and nanocarrier delivery are accelerating next-generation candidates. Yet inhibiting pyroptosis may heighten infection risk and demand brain-penetrant, cost-effective molecules. Judicious, biomarker-guided modulation of this fiery death program is therefore a promising but complex therapeutic strategy. This approach offers an increasingly tangible route to precision immunotherapy.

Keywords:

Gasdermin Axis Precision Control Pyroptosis

Article information

Journal

Journal of Medical Science, Biology, and Chemistry

Volume (Issue)

2(2), (2025)

Pages

169-179

Published

23-09-2025

How to Cite

Fadipe, D. P., Sonoiki, O. H., Bankole, E. A., Iwuala, L. C., Adedeji, S. J., Ezeah, C. G., & Oyortey, R. (2025). Drugging the Inflammasome Gasdermin Axis: Toward Precision Control of Pyroptosis. Journal of Medical Science, Biology, and Chemistry, 2(2), 169-179. https://doi.org/10.69739/jmsbc.v2i2.856

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