Description
CGP-37157 (75450-34-9) inhibits?the mitochondrial Na+-Ca2+?exchanger (NCX) in isolated heart mitochondria, IC50=0.36 μM.1?Does not inhibit the plasmalemmal NCX.2? Also inhibits voltage-gated Ca2+?channels in intact cells and therefore its use in cellular studies must employ adequate controls.3? Prevents sudden death in a Guinea pig model of heart failure.4?Displays pronounced cytoprotective effects in chromaffin cells5?and in neuronal injury models.6?Blood-brain barrier permeant.
Uses
7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one is a specific inhibitor of the mitochondrial Na+/Ca2+ exchanger.
Uses
CGP-37157 has been used as a mitochondrial sodium-calcium exchanger (mNCX) inhibitor to study the role of normal mitochondrial calcium dynamics in sustaining dendritic spinogenesis.
Definition
ChEBI: 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2-one is a benzothiazepine.
General Description
CGP-37157 is a benzothiazepine compound, which is derived from clonazepam. It functions as a sarco/endoplasmic reticulum Ca
2+ ATPase (SERCA) antagonist and ryanodine receptor channels (RyR) agonist. CGP-37157 regulates intracellular signaling of calcium in smooth, cardiac and skeletal muscle cells and non-muscle systems.
Biological Activity
Selective antagonist of the mitochondrial Na + -Ca 2+ exchanger (IC 50 = 0.4 μ M).
Biochem/physiol Actions
Specific inhibitor of mitochondrial Na+/Ca2+ exchange as well as sarcoplasmic reticulum calcium-stimulated ATPase and possibly other calcium channels.
References
1) Cox?et al.?(1993),?Selectivity of inhibition of Na(+)-Ca2+ exchange of heart mitochondria by benzothiazepine CGP-37157; J. Cardiovasc. Pharmacol.,?21?595
2) Namekata?et al. (2015),?Pharmacological discrimination of plasmalemmal and mitochondrial sodium-calcium exchanger in cardiomyocyte-derived H9c2 cells; Biol. Pharm. Bull,?38?147
3) Baron & Thayer (1997),?CGP37157 modulates mitochondrial Ca2+ homeostasis in cultured rat dorsal root ganglion neurons; Eur. J. Pharmacol.,?340?295
4) Liu?et al.?(2014),?Inhibiting mitochondrial Na+/Ca2+ exchange prevents sudden death in a guinea pig model of heart failure; Circ. Res.,?115?44
5) Nicolau?et al.?(2009),?Mitochondrial Na+/Ca2+-exchanger blocker CGP37157 protects against chromaffin cell death elicited by veratridine;?J. Pharmacol. Exp. Ther.,?330?844
6) Ruiz?et al. (2014),?CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons from excitotoxicity by blocking voltage gated Ca2+ channels; Cell Death Dis.,?5?e1156
