2. Academic Validation
  3. Benzothiazepine CGP37157 and its 2'-isopropyl analogue modulate Ca²⁺ entry through CALHM1

Benzothiazepine CGP37157 and its 2'-isopropyl analogue modulate Ca²⁺ entry through CALHM1

  • Neuropharmacology. 2015 Aug;95:503-10. doi: 10.1016/j.neuropharm.2015.02.016.
Ana J Moreno-Ortega 1,  Francisco J Martínez-Sanz 2,  Rocío Lajarín-Cuesta 2,  Cristóbal de Los Rios 3,  María F Cano-Abad 4
Affiliations

Affiliations

  • 1 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.
  • 2 Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain.
  • 3 Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, C/ Diego de León, 62, 28006, Madrid, Spain.
  • 4 Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain. Electronic address: [email protected].
PMID: 25908402 DOI: 10.1016/j.neuropharm.2015.02.016
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.

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.

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