Federal Project Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded $251,250 to the University of Massachusetts Medical School under the Allergy and Infectious Diseases Research program (CFDA 93.855) on June 10, 2026, with a completion date of May 31, 2028. This R21 project grant funds research to develop and validate a novel mitochondrial-targeted small-molecule inhibitor designated Compound-2 (C-2) that directly suppresses NLRP3 inflammasome activation. The research deliverables include elucidation of the mechanism by which C-2 inhibits NLRP3 activation, characterization of the molecular interaction between C-2 and the mitochondrial transporter SLC25A3, and validation of C-2 as a first-in-class inflammasome inhibitor through integrated biochemical, cellular, and in vivo experimental approaches.

This research addresses a significant unmet clinical need, as no FDA-approved therapies currently target the NLRP3 inflammasome directly, despite its central role in multiple inflammatory and degenerative diseases including gout, atherosclerosis, type 2 diabetes, and Alzheimer's disease. The project deliverables will contribute foundational knowledge regarding a previously unrecognized mitochondrial regulatory mechanism in inflammasome signaling and support therapeutic development of a selective small-molecule inhibitor with novel mechanisms of action that extend beyond downstream cytokine suppression to block inflammasome assembly and pyroptotic cell death.