JD02-174A is a highly potent, specific TRPM3 antagonist with IC50 of 0.46 nM in patch-clamp assays, shows significant analgesic efficacy.
JD02-174A inhibits TRPM3 activation by multiple agonists, including PS, CIM0216, and heat (36°C).
JD02-174A shows IC50 values of 43.85 and 1.92 nM against TRPM3 activation induced by 10 μM PS and 10 μM CIM0216, respectively, in calcium influx assays.
JD02-174A inhibits heat-activated (36°C) TRPM3 currents with IC50 of 5.79 nM in whole-cell patch-clamp recordings.
JD02-174A exhibits no inhibitory effect on TRPA1, TRPV1 and TRPM8 (IC50>30 uM).
JD02-174A inhibits human and mouse TRPM3 with IC50 values of 33.04 and 61.56 nM, respectively, with no statistically significant difference between the two homologs in calcium influx assays.
JD02-174A exhibits significant dose-dependent analgesic effects in murine models of neuropathic pain, inflammatory pain, and migraine, including chronic constriction injury (CCI) of the sciatic nerve, type 1 diabetic peripheral neuropathy (DPN), CFA-induced inflammatory pain, nitroglycerin (NTG)-induced acute migraine, hot plate assay, PS-induced acute pain, and oxaliplatin-induced neuropathic pain.
JD02-174A significantly increased the mechanical paw withdrawal threshold in a dose-dependent manner following oral administration at doses of 1, 3, and 10 mg/kg, with the 10 mg/kg dose showing the most pronounced effect in CCI rat model.