苯并硫氮杂䓬CGP37157及其2'-异丙基类似物通过CALHM1调节钙离子内流。
Benzothiazepine CGP37157 and its 2'-isopropyl analogue modulate Ca²⁺ entry through CALHM1.
作者信息
Moreno-Ortega Ana J, Martínez-Sanz Francisco J, Lajarín-Cuesta Rocío, de Los Rios Cristóbal, Cano-Abad María F
机构信息
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.
Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain.
出版信息
Neuropharmacology. 2015 Aug;95:503-10. doi: 10.1016/j.neuropharm.2015.02.016. Epub 2015 Apr 20.
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.
CALHM1是2008年发现的一种钙离子通道，它在神经元电活动及其他功能中起关键作用。然而，目前尚无已知的有效阻滞剂能够调节其钙离子处理能力。我们在此描述，苯并噻氮䓬CGP37157及其新合成的类似物ITH12575在低微摩尔浓度下可减少通过CALHM1的钙离子内流。这些结果可作为以CGP37157为先导化合物开发更具选择性的CALHM1配体的起点，这将有助于研究CALHM1在可兴奋细胞中控制胞内钙离子浓度方面的生理作用及其在中枢神经系统疾病中的意义。
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