title: Assessment of TRPM7 functions by drug-like small molecules.
abstract: Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a plasma membrane ion channel linked to a cytosolic protein kinase domain. Genetic inactivation of this bi-functional protein revealed its crucial role in Ca2+signalling, Mg2+metabolism, immune responses, cell motility, proliferation and differentiation. Malfunctions of TRPM7 are associated with anoxic neuronal death, cardiac fibrosis, tumour progression and macrothrombocytopenia. Recently, several groups have identified small organic compounds acting as inhibitors or activators of the TRPM7 channel. In follow-up studies, the identified TRPM7 modulators were successfully used to uncover new cellular functions of TRPM7 in situ including a crucial role of TRPM7 in Ca2+signaling and Ca2+dependent cellular processes. Hence, TRPM7 has been defined as a promising drug target. Here, we summarize the progress in this quickly developing field.
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, LMU, Munich, Germany. Electronic address: vladimir.chubanov@lrz.uni-muenchen.de.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chubanov
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, LMU, Munich, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferioli
authors.affiliation: Walther-Straub Institute of Pharmacology and Toxicology, LMU, Munich, Germany. Electronic address: thomas.gudermann@lrz.uni-muenchen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D016923:Cell Death / Q000187:drug effects; D004719:Endomyocardial Fibrosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D040181:Genetic Diseases, X-Linked / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D050053:TRPM Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013921:Thrombocytopenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D054852:Small Molecule Libraries; D050053:TRPM Cation Channels; C530168:Trpm6 protein, mouse; C421903:Trpm7 protein, mouse; D008274:Magnesium; D002118:Calcium
keywords: Calcium; Magnesium; TRP channel; TRPM6; TRPM7; α-kinase