Targeting the NLRP3 inflammasome for inflammatory disease therapy

The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a megadalton complex implicated in numerous inflammation-driven diseases including COVID-19, Alzheimer's disease, and gout. Although past efforts have focused on inhibiting IL-1β downstream of NLRP3 activation using drugs such as canakinumab, no FDA-approved NLRP3-targeted inhibitors are currently available. MCC950, a direct NLRP3 inhibitor, showed promise but exhibited off-target effects. Recent research has focused on optimizing the sulfonylurea-based MCC950 scaffold by leveraging recent structural and medicinal chemistry insights into the NLRP3 nucleotide-binding and oligomerization (NACHT) domain to improve solubility and clinical…

• NI
  National Institutes of Health
• UO
  University of California, Irvine
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: T32AI177324, K22AI139444
• DO
  Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

  Award: K22AI139444