title: Transient Receptor Potential Melastatin 8 Channel (TRPM8) Modulation: Cool Entryway for Treating Pain and Cancer.
abstract: TRPM8 ion channels, the primary cold sensors in humans, are activated by innocuous cooling (<28 °C) and cooling compounds (menthol, icilin) and are implicated in sensing unpleasant cold stimuli as well as in mammalian thermoregulation. Overexpression of these thermoregulators in prostate cancer and in other life-threatening tumors, along with their contribution to an increasing number of pathological conditions, opens a plethora of medicinal chemistry opportunities to develop receptor modulators. This Perspective seeks to describe current known modulators for this ion channel because both agonists and antagonists may be useful for the treatment of most TRPM8-mediated pathologies. We primarily focus on SAR data for the different families of compounds and the pharmacological properties of the most promising ligands. Furthermore, we also address the knowledge about the channel structure, although still in its infancy, and the role of the TRPM8 protein signalplex to channel function and dysfunction. We finally outline the potential future prospects of the challenging TRPM8 drug discovery field.
authors.affiliation: Instituto de Química Médica, IQM-CSIC. Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Pérez de Vega
authors.affiliation: Dipartimento di Farmacia, Università "Federico II" de Napoli , Via D. Montesano 49, 80131, Naples, Italy.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gómez-Monterrey
authors.affiliation: Instituto de Biología Molecular y Celular. Universitas Miguel Hernández . 03202 Alicante, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrer-Montiel
authors.affiliation: Instituto de Química Médica, IQM-CSIC. Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Muñiz
mesh_terms: D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D050053:TRPM Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050053:TRPM Cation Channels; C425966:TRPM8 protein, human