SB-366791

Description: SB-366791 is a competitive and selective cinnamide TRPV1 (Vanilloid receptor 1) antagonist identified via high-throughput screening of a large chemical library. SB-366791 has IC50 of 5.7+/-1.2 nM. SB-366791 showed a concentration-dependent potentiation of pH 5-induced 45Ca2+uptake in CHO cells expressing rat TRPV1 but not in untransfected cells. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.

References: Neuropharmacology. 2004 Jan; 46(1):133-49; Mol Pharmacol. 2005 Dec; 68(6):1524-33.