ASC inhibitor MM01 (MM01) is a first-in-class, specific small-molecule inhibitor of ASC protein that interferes with ASC speck formation, inhibited ASC-mediated pro-Casp-1 activation with IC50 of 0.5 uM.
MM01 does not target the active site of caspase-1.
MM01 (10 uM) inhibits ASC oligomerization/speck formation and facilitates ASC degradation in HEK293 cells.
MM01 inhibits ASC-dependent inflammasome activity, inhibits NLRP3-dependent inflammasome activity in vitro.
MM01 inhibits ASC-dependent inflammasome activity in stimulated murine peritoneal macrophages and in MSU-induced peritonitis mouse model.
MM01 (10mg/kg) efficiently suppressed MSU-induced IL-1β production and peritoneal neutrophil recruitment, with no effect on IL-6 and TNF-α secretion in murine mono-sodium urate (MSU)-induced model of peritonitis.
ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) is a protein of the innate immune system that participates in the formation of inflammasomes, which are macromolecular complexes responsible for the maturation and release of pro-inflammatory cytokines.