AMG-0347 (UNII-CD7L9290QR) is a small molecule inhibitor targeting TRPA1(transient receptor potential ankyrin 1) ion channels, a receptor found in sensory neurons and involved in the detection of pain and environmental stimuli. AMG-0347 acts by blocking the function of TRPA1 and has analgesic effects.

The inhibitory effects of AMG-0347 on the activation of TRPV1 channels by heat (45°C), protons (pH5), or capsaicin (500 nM) were evaluated using the 45 Ca2+ uptake assay in Chinese hamster ovary cells stably expressing rat or human TRPV1 channels.[1]
AMG-0347 demonstrated potent and selective antagonism against TRPV1 in vitro. Concentration-dependent inhibition was observed with IC50 values of 0.2 nM for heat-induced activation, 0.8 nM for proton-induced activation, and 0.7 nM for capsaicin-induced activation of rat TRPV1 channels. AMG-0347 did not exhibit blocking activity against other TRP channels, including TRPV2, TRPV3, TRPV4, TRP ankyrin-1, and TRP melastatin-8, with IC50 values of 10 μM.[1]

AMG0347 did not change the withdrawal threshold to mechanical stimulation or the guarding pain score. The withdrawal latency to heat increased from 3 h through 1 day after AMG0347 administration. AMG0347 prevented the decreases in heat withdrawal latency and mechanical withdrawal threshold caused by capsaicin infiltration and prevented the increase in activity caused by intrathecal capsaicin injection.[2]