Overview
- Gavva, N.R. et al. (2012) Mol. Pain 8, 36.
- Lehto, S.G. et al. (2015) Naunyn Schmiedebergs Arch. Pharmacol. 388, 465.
Alomone Labs AMG2850 blocks TRPM8 channels expressed in HEK 293 cells.Dose-response curve of TRPM8 inhibition by AMG2850 (#A-340), showing full inhibition at 2 µM (IC50 = 346 nM). Cells were loaded with Calcium-5 dye, incubated for 10 min with increasing concentrations of AMG2850, and activated by 30 nM icilin. Changes in intracellular Ca2+ following agonist application were detected as changes in 485 nm/525 nm fluorescence (RFU).
AMG2850 is a selective blocker of TRPM8 channels. The compound shows high selectivity towards TRPM8 over TRPV1 and TRPA1 channels. AMG2850 potently inhibits the menthol and cold-induced increase in intracellular Ca2+ in cells expressing rat TRPM8. In vitro, it was shown to inhibit rat TRPM8 against cold, menthol and icilin activation with IC50 of 7.3 nM, 156 nM and 204 nM, respectively1,2. AMG2850 is orally bioavailable and its plasma half-life (T1/2) in rats is 3.5 hours1,2.
TRPM8 is a Ca2+-permeable channel, a member of the ‘long' or melastatin (M) group of TRP channels and is activated by temperatures in the range of 8–28°C or by cooling compounds such as icilin. The TRPM8 gene is expressed and up-regulated in prostate cancer and other malignancies. TRPM8 channel is specifically expressed in temperature-sensing trigeminal and dorsal root ganglion neurons3,4.
