JT002 is a potent and selective inhibitor of NLRP3 inflammasome with IC50 of 6 nM (IL-1β production from hPBMCs), inhibits NLRP3 mediated cytokine production and pyroptosis.
JT002 potently inhibits IL-1α, IL-1β and IL-18 production with mean IC50 values of 3 nM, 4 nM and 4 nM, respectively, in human peripheral blood mononuclear cells (hPBMCs), with no effect on tumor necrosis factor alpha (TNFα) production up to 1 µM.
JT002 inhibits IL-1β production from human, mouse and rat PBMCs with mean IC50 values of 6, 25 and 159 nM, respectively.
JT002 potently inhibits IL-1β production under the alternative NLRP3 activating conditions with IC50 of 32 nM.
JT002 blocks canonical NLRP3-dependent IL-1β production activated downstream of ATP, nigericin, CHC or MSU with mean IC50 values of 5, 23, 2 and 3 nM, respectively and inhibits non-canonical induced IL-1β production with a mean IC50 value of 30 nM, with no inhibition of IL-1β production after NLRP1, NLRC4 or AIM2 activation at 10 uM.
JT002 blocks NLRP3 inflammasome complex formation and downstream pathway activation.
JT002 (30 mg/kg, oral) prevents disease progression in the Nlrp3A350V/+ knock-in murine model of Muckle Wells syndrome.
JT002 (25 mg/kg) attenuates airway inflammation and airway hyperresponsiveness in a mouse model of IL-17-dependent neutrophilic asthma.