2-[2-[4-(4-NITROBENZYLOXY)PHENYL]ETHYL]ISOTHIOUREA MESYLATE

Description

KB-R7943 (182004-65-5) is a potent and selective inhibitor of the reversed Na+/Ca2+ exchanger (NCE or NCX; IC50‘s = 1.2-2.4 μM in cardiomyocytes, smooth muscle cells, NCX1-transfected fibroblasts1; 0.7 μM in cultured rat forebrain2). KB-R7943 has also been shown to inhibit the mitochondrial Ca2+ uniporter (MCU) Ki = 5.5 μM.3 Recently shown to inhibit complex I in the mitochondrial respiratory chain (IC50 = 11.4 μM) and block NMDA receptors (IC50 = 13.4 μM).4

Uses

KB-R7943 Mesylate is a selective inhibitor of the reverse mode of Na+/Ca2+ exchange in cells expressing NCX1.

General Description

A cell-permeable inhibitor of the influx/reverse mode of the Na⁺/Ca²⁺ exchanger (NCX) (IC₅₀ = 4.3 μM for NCX1, 4.7 μM for NCX2, and 1.4 μM for NCX3). Directly modulates Na⁺/Mg²⁺ exchange in a Ca²⁺-dependent manner. Reported ot offer neuronal and cardio-protection against ischemic injury. Also inhibits nicotinic acetylcholine receptors and NMDA receptor channels (IC₅₀<10 μM).

Biological Activity

Potent, selective inhibitor of the reverse mode of the Na + /Ca 2+ exchanger (IC 50 = 0.7 mM). Does not affect Na + -dependent transport systems, Na + channels or ionotropic glutamate receptors.

Biochem/physiol Actions

Target IC50: 4.3 μM, 4.7 μM, and 1.4 μM for NCX1,NCX2, and NCX3, respectively

storage

Room temperature

References

1) Iwamoto et al. (1996), Novel Isothiourea Derivative Selectively Inhibits the Reverse Mode of Na+/Ca2+ Exchange in Cells Expressing NCX1; J. Biol .Chem., 271 22391 2) Hoyt et al. (1998) Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+ concentration increases in cultured rat forebrain neurons; Mol. Pharmacol., 53 742 3) Santo-Domingo et al. (2007) The plasma membrane Na+/Ca2+ exchange inhibitor KB-R7943 is also a potent inhibitor of the mitochondrial Ca2+ uniporter; Br. J. Pharmacol., 151 647 4) Brustovetsky et al. (2011) KB-R7943, an inhibitor of the reverse Na+/Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I; Br. J. Pharmacol,. 162 255