KB-R7943 mesylate is a widely used inhibitor of the reverse Na⁺/Ca²⁺ exchanger (NCX_rev) with IC₅₀ of 5.7±2.1 µM. KB-R7943 mesylate induces cancer cell death via activating the JNK pathway and blocking autophagic flux.

IC50: 5.7±2.1 µM (Na⁺/Ca²⁺ exchanger)^[1]

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 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 µM confirming the inhibition of NMDA receptors observed in electrophysiological experiments^[1]. _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)^[2]. KB-R7943 inhibits both I_hERG and native I_Kr 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. I_hERG inhibition by KB-R7943 exhibits both time- and voltage-dependence but shows no preference for inactivated over activated channels^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

427.50

C₁₇H₂₁N₃O₆S₂

182004-65-5

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

In Vitro: 

DMSO : ≥ 27 mg/mL (63.16 mM)

H₂O : 4.3 mg/mL (10.06 mM; Need warming)

* “≥” means soluble, but saturation unknown.

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.85 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.85 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.85 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.85 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.85 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.85 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Brustovetsky T, et al. KB-R7943, an inhibitor of the reverse Na+ /Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I. Br J Pharmacol. 2011 Jan;162(1):255-70.

  [2]. Barrientos G, et al. The Na+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate(KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels. Mol Pharmacol. 2009 Sep;76(3):560-8.

  [3]. Cheng H, et al. High potency inhibition of hERG potassium channels by the sodium-calcium exchange inhibitor KB-R7943. Br J Pharmacol. 2012 Apr;165(7):2260-73.

  [4]. Long Z, et al. The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux. Oncotarget. 2016;7(27):42059-70.

EK 293 cells stably expressing the _wtRyR1 (_wtRyR1-HEK 293) are maintained in Dulbecco’s modified Eagle’s medium supplemented with 2 mM glutamine, 100 μg/mL streptomycin, 100 U/mL penicillin, 1 mM sodium pyruvate, and 10% fetal bovine serum at 37°C under 5% CO₂. _wtRyR1-HEK 293 cells are loaded with 5 μM Fluo-4 acetoxymethyl ester at 37°C for 30 min to measure Ca²⁺ transients in an imaging buffer consisting of 140 mM NaCl, 5 mM KCl, 2 mM MgCl₂, 2 mM CaCl₂, 10 mM HEPES, and 10 mM glucose, pH 7.4, supplemented with 0.05% bovine serum albumin. The cells are washed three times with imaging buffer and additionally incubated for 20 min at room temperature. Dye-loaded cells are washed three times with imaging buffer and imaged with a charge-coupled device camera with a 40× objective lens attached to an IX-71 microscope. The sequence of images is captured and monitored using EasyRatioPro. Caffeine dissolved in the imaging buffer is focally applied for 15 s using AutoMate Scientific. KB-R7943 is dissolved in the imaging buffer, and _wtRyR1-HEK 293 cells are incubated for 10 min before the application of caffeine^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Brustovetsky T, et al. KB-R7943, an inhibitor of the reverse Na+ /Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I. Br J Pharmacol. 2011 Jan;162(1):255-70.

  [2]. Barrientos G, et al. The Na+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate(KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels. Mol Pharmacol. 2009 Sep;76(3):560-8.

  [3]. Cheng H, et al. High potency inhibition of hERG potassium channels by the sodium-calcium exchange inhibitor KB-R7943. Br J Pharmacol. 2012 Apr;165(7):2260-73.

  [4]. Long Z, et al. The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux. Oncotarget. 2016;7(27):42059-70.