OLT1177 (Dapansutrile) is an orally active β-sulfonyl nitrile molecule, inhibits activation of the NLRP3 inflammasome, prevents NLRP3-ASC, as well as NLRP3-caspase-1 interaction, thus inhibiting NLRP3 inflammasome oligomerization.
OLT1177 reduces IL-1β and IL-18 release following canonical and noncanonical NLRP3 inflammasome activation at nanomolar concentrations.
OLT1177 decreased IL-1β levels by 60% and IL-18 by 70% at concentrations 100-fold lower in vitro in LPS-stimulated human blood-derived macrophages.
OLT1177 also reduced IL-1β release and caspase-1 activity in freshly obtained human blood neutrophils.
OLT1177 inhibited LPS-induced IL-1β release by 84% and 36% in monocytes isolated from patients with cryopyrin-associated periodic syndrome (CAPS).
OLT1177 (1 and 10 µM) reduced ATPase activity of recombinant NLRP3.
OLT1177 significantly lowered steady-state levels of phosphorylated NF-κB and IkB kinase in spleen cells from OLT1177-treated mice.