placeholder image

NLRP3 inhibitors

A key mediator of chronic inflammation that develops with age

NLRP3 is a critical component of the inflammasome, a protein complex that assembles in response to infection and tissue damage and results in inflammation needed to promote healing. However, chronic inflammasome activation leads to pathologic inflammation that drives a vast number of immunologic and fibrotic disorders. Analysis of BioAge’s proprietary longitudinal human aging cohorts revealed that NLRP3 levels rise with age are associated with all-cause mortality.

BioAge has discovered a family of structurally and chemically novel NLRP3 inhibitors. We are developing two compounds in parallel–one that enters the central nervous system, and the other that is selective for peripheral tissues–to optimize our ability to address the many age-related diseases driven by chronic inflammasome activation.

placeholder image

BioAge’s novel NLRP3 inhibitors correct chronic

inflammasome activation that is associated with

aging and drives a broad range of diseases

BioAge’s novel NLRP3 inhibitors correct

chronic inflammasome activation that is

associated with aging and drives a

broad range of diseases

BioAge’s novel NLRP3 inhibitors

correct chronic inflammasome

activation that is associated with

aging and drives a broad range of

diseases

Young
Absence of immune stimuli
Inactive NLRP3
Immune stimuli
NLRP3 inflammasome assembly and activation
Acute cytokine release: (IL-1β, IL-18)

Acute inflammation to enable immune respons to pathogen

Old
Immune system priming: ↑ NLRP3, ASC, pro-caspase
  • NLRP3
  • ACS
  • Pro-caspase-1
Overactive NLRP3 inflammasome
Exaggerated proinflammatory signals: ytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3 inhibitor

Prolonged inflammation, even in the absence of pathogen

Acute cytokine release: (IL-1β, IL-18)

Acute inflammation to enable immune respons to pathogen

Exaggerated proinflammatory signals: ytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3 inhibitor

Prolonged inflammation, even in the absence of pathogen

photo

BioAge collaborator spotlight

Chronic activation of the NLRP3 inflammasome is associated with aging and is a major contributor to the pathologic inflammation that drives or exacerbates multiple metabolic, immunologic, and fibrotic disorders, as well as neurodegenerative conditions such as Parkinson’s and Alzheimer’s. Inhibition of NLRP3 using small-molecules thus has the potential to treat a broad spectrum of age-related diseases.

Rebecca Coll, PhD

Wellcome Wolfson Institute for Experimental Medicine

Queen's University Belfast

Left gradient Right gradient