GDC-0334 (GDC0334) is a highly potent, selective, orally bioavailable TRPA1 antagonist with IC50 of 1.7 nM in cell-based assays.GDC-0334 demonstrated potent TRPA1 inhibition in several species, including human (IC50=1.7 nM), cynomolgus (IC50=3.6 nM), mouse (IC50=2.7 nM), guinea pig (IC50=11.1 nM), and dog (IC50=102 nM).GDC-0334 displays good selectivity against human TRPV1, TRPM8, and TRPC6 (all IC50s>10 uM).GDC-0334 also inhibits calcium flux in human primary cells, HASMCs and HLFs, treated with the TRPA1 agonist AITC.GDC-0334 suppresses AITC-induced edema in vivo in rat (1-10 mg/kg), reduces OVA-induced asthma model in rats and guinea pigs and guinea pig model of cough.GDC-0334 is a potent inhibitor of AITC-induced dermal blood flow (DBF) in vivo in rats and guinea pigs, reduces AITC-induced perfusion and nocifensive behavior in rats and itch and pain scores in humans.
