A nanomolar inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
A member of NOD-like receptor (NLR) family namely, pyrin
domain–containing protein 3 (NLRP3) inflammasome is a component of the
inflammatory process. Its aberrant activation is pathogenic in inherited
disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex
diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and
atherosclerosis. NLRP3 deregulation is also associated in cancer pathways.
Researchers have reported the activity of MCC950, a nanomolar
inhibitor of canonical and noncanonical NLRP3 activation. The MCC950
specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1
inflammasomes. MCC950 reduced interleukin-1ß (IL-1ß) production in vivo and
attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a
disease model of multiple sclerosis.
MCC950 has potential to be the therapeutic for
NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases,
and a tool for further study of the NLRP3 inflammasome in human health and
disease.
Reference:
1. Cooper, M. A.; et. al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. 2015, Nat Med doi:10.1038/nm.3806
