KB-R7943 Mesylate is a potent and selective inhibitor used to reverse mode of the Na+/Ca2+ exchanger with IC50 value of 0.7 μM. It also inhibits the mitochondrial Ca2+ uniporter with IC50 value of 5.5 μM.
KB-R7943 mesylate is a widely used inhibitor of the reverse Na+/Ca2+ exchanger (NCXrev) with IC50 of 5.7±2.1 µM. KB-R7943 mesylate induces cancer cell death via activating the JNK pathway and blocking autophagic flux. KB-R7943 mesylate blocks NMDAR-mediated ion currents, and inhibits NMDA-induced increase in cytosolic Ca2+ with IC50=13.4±3.6 µM 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 µM. In addition to NCXrev, 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 µM confirming the inhibition of NMDA receptors observed in electrophysiological experiments[3]. wtRyR1-HEK 293 pretreated with KB-R7943 (10 μM, 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)[4]. KB-R7943 inhibits both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ~89 and ~120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. IhERG inhibition by KB-R7943 exhibits both time- and voltage-dependence but shows no preference for inactivated over activated channels[5]. In fish cardiomyocytes IKATP was blocked by KB-R7943 with an IC50 value of 3.14×10(-7) M, while in mammalian cells IC50 was 2.8×10(-6) M (P<0.05). 10(-5) M KB-R7943 inhibited CCCP-induced IKATP by 99.9±0.13% and 97.5±1.2% in crucian carp and mouse ventricular myocytes, respectively[6].
KB-R7943 mesylate 细胞实验
Cell Line
Concentration
Treated Time
Description
References
WT atrial myocytes
1 µM
Heart Rhythm. 2018 Aug;15(8):1233-1241
human embryonic stem cells (H9 and H7)
100 µmol/L
KB-R7943, as an NCX inhibitor, induced rapid Ca2+ transients in both H9 and H7 human embryonic stem cells, indicating the functional role of NCX in hESCs.
Acta Pharmacol Sin. 2017 Dec;38(12):1663-1672
porcine retinal venules
10 μmol/L
30 minutes
KB-R7943 inhibited the hyperglycemia-enhanced constriction of retinal venules to ET-1, U46619, and norepinephrine.
Diabetes. 2019 Aug;68(8):1624-1634
Pak1−/− atrial myocytes
1 µM
15 minutes
KB-R7943 attenuated the AngII-induced increase in diastolic [Ca2+]i and Ca2+ transient amplitude in Pak1−/− cells
Heart Rhythm. 2018 Aug;15(8):1233-1241
human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)
3 µM or 10 µM
4-5 minutes
KB-R7943 blocked the arrhythmias caused by -AA+YWF treatment, indicating the role of NCX reverse mode in arrhythmogenesis.
Int J Mol Sci. 2024 Apr 30;25(9):4932
Paediatric glioblastoma cell line SF188
0.1–100 μM
72 hours
KB-R7943 inhibited the viability of SF188 cells in a dose-dependent manner.
Br J Pharmacol. 2019 Aug;176(15):2691-2707
Human glioblastoma cell line U251
0.1–100 μM
72 hours
KB-R7943 inhibited the viability of U251 cells, reducing it to 50–60%, 7–18%, and 2–3% of control level at 20, 50, and 100 μM concentrations, respectively.
Br J Pharmacol. 2019 Aug;176(15):2691-2707
KB-R7943 mesylate 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Neonatal monosodium glutamate (MSG)-treated rat model
Intracerebroventricular injection
62.5 pmol
Single administration
To evaluate the control effect of KB-R7943 on 4-aminopyridine (4-AP)-induced epileptiform activity. Results showed that KB-R7943 significantly reduced 4-AP-induced epileptiform activity in MSG-treated rats.
J Biomed Sci. 2017 May 9;24(1):27
Rat
Isolated rat heart ischemia/reperfusion injury model
Perfusion
10 μM
1 min before and 3-min throughout the Ca2+-free solution perfusion, as well as 3 min after restoring normal KH solution
KB-R7943 alleviated heart injury and calpain activity
Cell Death Dis. 2020 May 21;11(5):388
Pigs
Streptozotocin-induced diabetes model
Extraluminal pretreatment
10 μmol/L
Single treatment, lasting at least 30 minutes
KB-R7943 inhibited the hyperglycemia-enhanced constriction of retinal venules to ET-1, U46619, and norepinephrine.
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