MCC-950 (210826-40-7) was originally found to act as a cytokine release inhibitory drug (CRID), arresting activated monocytes and preventing activation of caspase-1.1 Discovered to be a novel inhibitor of the NLRP3 and AIM2 inflammasomes.2 MCC-950 blocks canonical and noncanonical NLRP3 activation at nanomolar concentrations.3 Inhibits interleukin 1β (IL-1β) secretion in vivo and attenuates the severity of experimental autoimmune encephalomyelitis (an MS disease model).3 Disrupts the interaction between AIM2 and ASC in a reconstituted cell-free inflammasome.4 MCC-950 is a valuable new tool for exploring the pathophysiology of NLRP3.
1) Laliberte et al. (2003), Glutathione s-transferase omega 1-1 is a target of cytokine release inhibitory drugs and may be responsible for their effect on interleukin-1beta posttranslational processing; J. Biol. Chem., 278 16567
2) Coll et al. (2011), The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes; Clin. PLoS One, 6(12) e29539
3) Coll et al. (2015), A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory disease; Nat. Med., 21 248
4) Kaneko et al. (2015), Reconstituted AIM2 inflammasome in cell-free system; J. Immunol. Methods, 426 76