NLRP3 Inhibitors
NLRP3 Inhibitors – Target Pipeline List 04/2019
Targets: NLRP3; Nucleotide-binding oligo-merization (NOD)-like Receptor Family Pyrin Domain Containing Protein 3
This Target Pipeline List provides an overview of small molecule inhibitors of NLRP3 in development for treatment of chronic inflammatory diseases.
A spectrum of inflammatory diseases are associated with mutations in the NLR gene family. The NLR family is composed of 23 cytosolic proteins with variable recognition motifs that are responsible for detecting cellular threats using pathogen-associated molecular patterns (PAMP) or damage-associated molecular patterns (DAMP). After recognition, some NLRs change shapes to assemble a multi-protein structure known as an inflammasome, which activates inflammatory processes.
By blocking inflammasome activity, small-molecule inhibitors may help reduce overactive cytokine production and stop inflammatory signaling.
Nembers of the NLR family include NLRP1, NLRP3, NLRP6, NLRP10 and NLRC4. By targeting components of the inflammasome, the potential exists for NLR inhibitors to be used for multiple indications and to serve as innate immune modulators for the treatment of liver fibrosis/non-alcoholic steatohepatitis (NASH), neurodegeneration/Alzheimer’s or Parkinson’s disease, cardio-metabolic diseases such as atherosclerosis and type 2 diabetes, gout, age-related macular degeneration and autoimmune diseases that include systemic sclerosis, inflammatory bowel disease (IBD), vitiligo, type 1 diabetes, celiac disease, systemic lupus erythematosus and rheumatoid arthritis.
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