Disease relevance of CGP-37157

• Application of CGP-37157 significantly inhibited effluxes of all FFAs during both ischemia and reperfusion [1].
• We evaluated the effects of 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157) (50 muM), a specific inhibitor of mitochondrial Na(+)/Ca(2+) exchange, applied topically onto rat cerebral cortex during ischemia-reperfusion injury [1].

High impact information on CGP-37157

• Using indo-1 microfluorometry and a specific inhibitor of the mitochondrial Na+/Ca2+ exchanger, CGP-37157, we have demonstrated that mitochondria accumulate large quantities of Ca2+ during a toxic glutamate stimulus and further that Ca2+ efflux from mitochondria contributes to the prolonged [Ca2+]i elevation after glutamate removal [2].
• Furthermore, when CGP-37157, a specific inhibitor of the mitochondrial NCX, was applied during MI, the second-phase drop of [Na+]m was completely abolished [3].
• Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP-37157 (50 microM) dramatically prolonged the post-stimulation decay of mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and reduced the amplitude of endplate potentials evoked after the end of a stimulus train in the presence of both low and normal bath [Ca2+] [4].
• Under Na+-free conditions, or when CGP-37157, a specific inhibitor of the mitochondrial NCE, was used, no drop in [Ca2+]i was seen during MI, whereas the MI-induced increase in mitochondrial rhod 2 fluorescence was strongly reduced [5].
• Ruthenium red and the Na+/Ca2+ exchange inhibitor CGP 37157 blocked calcium cycling and prevented mitochondrial shape changes in digitonin-treated, but not ionophore-treated astrocytes [6].

Biological context of CGP-37157

• Our data suggest that the effects of CGP-37157 on neuronal Ca(2+) homeostasis include inhibition of certain plasmalemmal NCX isoform(s) [7].
• CGP-37157 inhibited the activity of mitochondrial Na(+)-Ca2+ exchange in a dose-dependent manner (IC50 0.36 microM) [8].
• Our results show that, under these treatment conditions, inhibiting the Na(+)/Ca(2+) exchanger using benzothiazepin CGP-37157 (CGP) did not induce apoptosis [9].

Anatomical context of CGP-37157

• Inhibition of L-type Ca(2+) channel by mitochondrial Na(+)-Ca(2+) exchange inhibitor CGP-37157 in rat atrial myocytes [10].
• CGP-37157, at concentrations < or = 10 microM, had no effect on the activities of the Na(+)-Ca2+ exchanger and Na(+)-K(+)-ATPase in isolated cardiac sarcolemmal vesicles or on activity of the Ca(2+)-ATPase in isolated cardiac sarcoplasmic reticulum vesicles [8].
• Selectivity of inhibition of Na(+)-Ca2+ exchange of heart mitochondria by benzothiazepine CGP-37157 [8].
• The objective was to determine if the benzothiazepine compound CGP-37157 selectively inhibits the Na(+)-Ca2+ exchanger of cardiac mitochondria without affecting the L-type voltage-dependent calcium channel, the Na(+)-Ca2+ exchanger, or the Na(+)-K(+)-ATPase of the cardiac sarcolemma, or the Ca(2+)-ATPase of the cardiac sarcoplasmic reticulum [8].

Associations of CGP-37157 with other chemical compounds

• Ca(2+) was extruded from mitochondria more slowly than it entered, and much of this efflux could be blocked by CGP-37157, a selective inhibitor of mitochondrial Na(+)-Ca(2+) exchange [11].

Gene context of CGP-37157

• The electrophysiological effects of the benzothiazepine 7-chloro-3,5-dihydro-5-phenyl-1H-4,1-benzothiazepine-2-one (CGP-37157) (CGP) were investigated on the canine (NCX1.1) and Drosophila (CALX1.1) plasmalemmal Na+-Ca2+ exchangers [12].

References