AMG 333 is an antagonist of transient receptor potential melastatin 8 (TRPM8; IC50s = 13 and 20 for the human and rat channels, respectively).1 It is selective for TRPM8 over TRP vanilloid 1 (TRPV1), TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1; IC50s = >20, >20, >20, and >40 ?M, respectively), as well as a panel of 100 kinases and 144 additional targets at 1 and 10 ?M, respectively. AMG 333 (0.6-3 mg/kg) decreases wet-dog shakes, a behavioral marker of cold sensation, induced by the TRPM8 agonist icilin in rats.
1.Horne, D.B., Biswas, K., Brown, J., et al.Discovery of TRPM8 antagonist (S)-6-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic acid (AMG 333), a clinical candidate for the treatment of migraineJ. Med. Chem.61(18)8186-8201(2018)