CGP 37157 is a potent and selective antagonist of the mitochondrial Na+-Ca2+ exchanger with IC50 value of 0.4 μM [1].
The mitochondrial Na+-Ca2+ exchanger (mNCE) is an antiporter membrane protein and removes a single Ca2+ in exchange for the import of three Na+. Mitochondrial Ca2+ uptake plays a critical role in the control of apoptosis, regulation of metabolic activity and Ca2+ shaping and buffering of Ca2+ signals [2].
CGP 37157 is a selective mNCE antagonist. In isolated heart mitochondria, CGP-37157 inhibited the activity of mNCE with IC50 value of 0.36 μM in a dose-dependent way [1]. In human and mouse β-cells, CGP-37157 inhibited KCl- and glucose-stimulated Ca2+ signals in a dose-dependent way and decreased insulin secretion from perifused islets [2]. In rat forebrain neurons, CGP-37157 consistently caused a rapid fall in Ca2+ influx stimulated by glutamate, which suggested the recovery of Ca2+ influx induced by glutamate was regulated via mNCE [3]. In rat dorsal root ganglion neurons, CGP37157 inhibited depolarization-induced Ca2+ influx and mitochondrion-mediated Ca2+ influx [4].
References:
[1]. Cox DA, Conforti L, Sperelakis N, et al. Selectivity of inhibition of Na(+)-Ca2+ exchange of heart mitochondria by benzothiazepine CGP-37157. J Cardiovasc Pharmacol, 1993, 21(4): 595-599.
[2]. Luciani DS, Ao P, Hu X, et al. Voltage-gated Ca(2+) influx and insulin secretion in human and mouse beta-cells are impaired by the mitochondrial Na(+)/Ca(2+) exchange inhibitor CGP-37157. Eur J Pharmacol, 2007, 576(1-3): 18-25.
[3]. White RJ, Reynolds IJ. Mitochondria accumulate Ca2+ following intense glutamate stimulation of cultured rat forebrain neurones. J Physiol, 1997, 498 ( Pt 1): 31-47.
[4]. Baron KT, Thayer SA. CGP37157 modulates mitochondrial Ca2+ homeostasis in cultured rat dorsal root ganglion neurons. Eur J Pharmacol, 1997, 340(2-3): 295-300.
