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.