TRPM8 Biology and Medicinal Chemistry

Jeff      DeFalco; Matthew      A.J. Duncton; Daniel      Emerling

Abstract

TRPM8 belongs to the TRPM Melastatin subfamily of Transient Receptor Potential (TRP) ion channels. Activated by cool temperatures and mimetic ligands, such as menthol and icilin, TRPM8 has been shown to play a role in thermoreception and is expressed in peripheral nerves. TRPM8 is also expressed in other tissues which are not exposed to temperature fluctuations, such as the prostate. The recent advancement of a TRPM8 agonist into the clinic for the treatment of prostate cancer suggests that the channel plays a role in some human pathologies. As more drug-like and selective agonists and antagonists of TRPM8 become available, in vivo pharmacology studies will complement already published knockout data to further our understanding of the role of TRPM8 in human disease.

Keywords: TRP, TRPM8, menthol, icilin, agonist, antagonist, ligand, Medicinal Chemistry, mimetic ligands, menthol and icilin, peripheral nerves, prostate cancer, knockout data, TRPM8 Protein, TRPM8 BIOLOGY