title: Benzothiazepine CGP37157 and its 2'-isopropyl analogue modulate Ca²⁺ entry through CALHM1.
abstract: CALHM1 is a Ca(2+) channel discovered in 2008, which plays a key role in the neuronal electrical activity, among other functions. However, there are no known efficient blockers able to modulate its Ca(2+) handling ability. We herein describe that benzothiazepine CGP37157 and its newly synthesized analogue ITH12575 reduced Ca(2+) influx through CALHM1 at low micromolar concentrations. These results could serve as a starting point for the development of more selective CALHM1 ligands using CGP37157 as a hit compound, which would help to study the physiological role of CALHM1 in the control of [Ca(2+)]cyt in excitable cells, as well as its implication in CNS diseases.
authors.affiliation: Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain; Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, C/ Diego de León, 62, 28006, Madrid, Spain.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Moreno-Ortega
authors.affiliation: Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Martínez-Sanz
authors.affiliation: Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Lajarín-Cuesta
authors.affiliation: Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, C/ Diego de León, 62, 28006, Madrid, Spain.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: de Los Rios
authors.affiliation: Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain. Electronic address: maria.cano@uam.es.
authors.forename: María F
authors.initials: MF
authors.lastname: Cano-Abad
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003035:Cobalt / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011110:Polymorphism, Genetic; D061209:Proton Ionophores / Q000494:pharmacology; D013841:Thiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection
chemical_list: C000605974:7-chloro-5-(2-isopropylphenyl)-3,5-dihydro-4,1-benzothiazepin-2-(1H)-one; C530077:CALHM1 protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002412:Cations; D007211:Indoles; D008562:Membrane Glycoproteins; D061209:Proton Ionophores; D013841:Thiazepines; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D003035:Cobalt; D002998:Clonazepam; C079032:CGP 37157; C010119:latrepirdine; D002118:Calcium
keywords: Benzothiazepines; CGP37157; Calcium homeostasis modulator 1 (CALHM1); Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; Dimebolin; FCCP; ITH12575; Neurodegenerative diseases; PubChem CID: 197033; PubChem CID: 2688; PubChem CID: 3330