A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
PROJECT ABSTRACT Inflammasomes are multiprotein complexes of the innate immune system that assemble upon detecting specific molecular patterns associated with pathogens and cellular damage. Once assembled, activated inflammasomes trigger a cascade of downstream events that culminate in cell death and inflammation. Aberrant activation of the NLRP3 inflammasome contributes to the pathogenesis of numerous inflammatory and degenerative diseases, including gout, atherosclerosis, type 2 diabetes, and Alzheimer’s disease. Despite its central role in innate immunity and inflammation, there are no FDA-approved therapies that directly target the NLRP3 inflammasome. Current strategies rely on biologics that inhibit downstream pro-inflammatory cytokines produced from inflammasome activation, such as interleukin-1β (IL-1β), but do not block upstream inflammasome assembly or pyroptotic cell death, highlighting a critical unmet need for selective small-molecule inhibitors with novel mechanisms of action. To address this gap, we identified a covalent small molecule, Compound-2 (C-2), that robustly inhibits NLRP3 inflammasome activation in murine and human immune cells. C-2 suppresses multiple downstream events triggered by inflammasome activation, including IL-1β secretion and pyroptosis, with no apparent toxicity. Chemoproteomic profiling revealed that C-2 interacts with SLC25A3, a mitochondrial phosphate and copper transporter, suggesting a previously unrecognized regulatory node in inflammasome signaling. This R21 project aims to (1) elucidate the mechanism by which C-2 suppresses NLRP3 activation and (2) define the molecular interaction between C-2 and SLC25A3 and its functional consequences. Our studies will integrate biochemical, cellular, and in vivo approaches to uncover a novel mitochondrial mechanism of inflammasome regulation and validate C-2 as a first-in-class inflammasome inhibitor. Successful completion of this project will lay the foundation for future therapeutic development targeting mitochondrial- inflammasome crosstalk in inflammatory disease.
Grant Summary
A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $251K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $251K
2028-05-31
- 1Confirm your organization is eligible for A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation: Frequently Asked Questions
Who is eligible for the A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation?
A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation provide?
A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation provides up to $251K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation deadline?
Applications for A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation?
To apply for A Novel Mitochondrial-Targeted Inhibitor of NLRP3 Inflammasome Activation, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.