KB-R7943 (mesylate)

182004-65-5

C17H21N3O6S2

DMSO : >= 27 mg/mL (63.16 mM); H2O : 4.3 mg/mL (10.06 mM; Need warming)

Membrane Transporter/Ion Channel; Autophagy

KB-R7943 mesylate is a widely used inhibitor of the reverse Na⁺/Ca²⁺ exchanger (NCX_rev) with IC₅₀ of 5.7+/-2.1 uM. KB-R7943 mesylate induces cancer cell death via activating the JNK pathway and blocking autophagic flux. IC50 & Target: IC50: 5.7+/-2.1 uM (Na⁺/Ca²⁺ exchanger)^[1] In Vitro: KB-R7943 mesylate blocks NMDAR-mediated ion currents, and inhibits NMDA-induced increase in cytosolic Ca²⁺ with IC₅₀=13.4+/-3.6 uM but accelerates calcium deregulation and mitochondrial depolarization in glutamate-treated neurons. KB-R7943 depolarizes mitochondria in a Ca²⁺-independent manner. KB-R7943 inhibits 2, 4-dinitrophenol-stimulated respiration of cultured neurons with IC₅₀=11.4+/-2.4 uM. In addition to NCX_rev, KB-R7943 dose-dependently and reversibly blocked ion currents elicited by NMDA. KB-R7943 dose-dependently inhibits NMDA-induced increases in [Ca²⁺]_c with IC₅₀=13.4+/-3.6 uM confirming the inhibition of NMDA receptors observed in electrophysiological experiments^[1]. _wtRyR1-HEK 293 pretreated with KB-R7943 (10 uM, 10 min) dissolved in the bulk perfusion exhibited significantly attenuated responses to caffeine. In this regard, KB-R7943 produced more pronounced inhibition of caffeine-induced Ca²⁺ release elicited by 1 mM compared with 0.5 and 0.75 mM (60 versus 58 versus 37%, p<0.05, respectively)^[2]. KB-R7943 inhibits both I_hERG and native I_Kr rapidly on membrane depolarization with IC₅₀ values of ca.89 and ca.120 nM, respectively, for current tails at ?40 mV following depolarizing voltage commands to +20 mV. I_hERG inhibition by KB-R7943 exhibits both time- and voltage-dependence but shows no preference for inactivated over activated channels^[3].