amg-9810

Description: AMG9810 is a nove, potent, selective and competitive antagonist of vanilloid receptor 1 (TRPV1) with IC50 values of 24.5 and 85.6 nM for human and rat TRPV1, repectively. AMG9810 promotes mouse skin tumor development. The topical application of AMG9810 resulted in a significant increase in the expression level of the epidermal growth factor receptor (EGFR) and its downstream Akt/mammalian target of rapamycin (mTOR)-signaling pathway. This increase was not only observed in AMG9810-treated tumor tissue but was also found in skin tissue treated with AMG9810. In telomerase-immortalized primary human keratinocytes, AMG9810 promoted proliferation that was mediated through the EGFR/Akt/mTOR-signaling pathway. In summary, our data suggest that the TRPV1 antagonist, AMG9810, promotes mouse skin tumorigenesis mediated through EGFR/Akt/mTOR signaling. Thus, the application of this compound for pain relief might increase the risk of skin cancer.

References: Carcinogenesis. 2011 May; 32(5):779-85; J Pharmacol Exp Ther. 2005 Apr; 313(1):474-84.