Description
CGP-37157 (75450-34-9) inhibitsthe mitochondrial Na+-Ca2+exchanger (NCX) in isolated heart mitochondria, IC50=0.36 μM.1Does 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.4Displays pronounced cytoprotective effects in chromaffin cells5and in neuronal injury models.6Blood-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] D A COX. Selectivity of inhibition of Na(+)-Ca2+ exchange of heart mitochondria by benzothiazepine CGP-37157.[J]. Journal of Cardiovascular Pharmacology, 1993, 21 4: 595-599. DOI:
10.1097/00005344-199304000-00013[2] IYUKI NAMEKATA Hikaru T Shogo Hamaguchi. Pharmacological discrimination of plasmalemmal and mitochondrial sodium-calcium exchanger in cardiomyocyte-derived H9c2 cells.[J]. Biological & pharmaceutical bulletin, 2015, 38 1: 147-150. DOI:
10.1248/bpb.b14-00525[3] KYLE T BARON Stanley A T. CGP37157 modulates mitochondrial Ca2+ homeostasis in cultured rat dorsal root ganglion neurons[J]. European journal of pharmacology, 1997, 340 2: Pages 295-300. DOI:
10.1016/s0014-2999(97)01433-7[4] TING LIU. Inhibiting mitochondrial Na+/Ca2+ exchange prevents sudden death in a Guinea pig model of heart failure.[J]. Circulation research, 2014, 115 1: 44-54. DOI:
10.1161/circresaha.115.303062[5] SANTOS M NICOLAU. Mitochondrial Na+/Ca2+-exchanger blocker CGP37157 protects against chromaffin cell death elicited by veratridine.[J]. Journal of Pharmacology and Experimental Therapeutics, 2009, 330 3: 844-854. DOI:
10.1124/jpet.109.154765[6] A RUIZ C M E Alberdi. CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons from excitotoxicity by blocking voltage-gated Ca2+ channels[J]. Cell Death & Disease, 2014, 5 4: e1156-e1156. DOI:
10.1038/cddis.2014.134
