KB-R7943

KB-R7943 is a potent, selective inhibitor of the reverse mode of the Na+/Ca2+ exchanger (IC50 = 0.7 μM). KB-R7943 does not modify secondary pathology in the thalamus following focal cerebral stroke in rats. KB-R7943 blocks opening of the mitochondrial permeability transition pore. KB-R7943 restores endothelium-dependent relaxation induced by advanced glycosylation end products in rat aorta. KB-R7943 inhibits high glucose-induced endothelial ICAM-1 expression and monocyte-endothelial adhesion.

Product information

CAS Number: 182004-65-5

Molecular Weight: 427.50

Formula: C17H21N3O6S2

Synonym:

KB-R7943 mesylate

KB-R7943

KB R7943

KB-R 7943

Related CAS Number:

182004-64-4 (free base)

Chemical Name: 2-[2-[4-(4-Nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate

Smiles: CS(O)(=O)=O.NC(=N)SCCC1C=CC(=CC=1)OCC1C=CC(=CC=1)[N+]([O-])=O

InChiKey: WGIKEBHIKKWJLG-UHFFFAOYSA-N

InChi: InChI=1S/C16H17N3O3S.CH4O3S/c17-16(18)23-10-9-12-3-7-15(8-4-12)22-11-13-1-5-14(6-2-13)19(20)21;1-5(2,3)4/h1-8H,9-11H2,(H3,17,18);1H3,(H,2,3,4)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

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. 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). 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.

References:

1. Chang PC, Wo HT, Lee HL, Wen MS, Chou CC. Paradoxical effects of KB-R7943 on arrhythmogenicity in a chronic myocardial infarction rabbit model. J Cardiol. 2015 Jul;66(1):80-7. doi: 10.1016/j.jjcc.2014.08.002. Epub 2014 Sep 16. PubMed PMID: 25241015.
2. Lipsanen A, Parkkinen S, Khabbal J, Mäkinen P, Peräniemi S, Hiltunen M, Jolkkonen J. KB-R7943, an inhibitor of the reverse Na(+)/Ca(2+) exchanger, does not modify secondary pathology in the thalamus following focal cerebral stroke in rats. Neurosci Lett. 2014 Sep 19;580:173-7. doi: 10.1016/j.neulet.2014.08.003. Epub 2014 Aug 12. PubMed PMID: 25123443.
3. Abramochkin DV, Vornanen M. Inhibition of the cardiac ATP-dependent potassium current by KB-R7943. Comp Biochem Physiol A Mol Integr Physiol. 2014 Sep;175:38-45. doi: 10.1016/j.cbpa.2014.05.005. Epub 2014 May 17. PubMed PMID: 24845199.
4. Ren Y, Deng L, Cai Y, Lv Y, Jia D. The protective effect of Na+/Ca2+ exchange blocker kb-r7943 on myocardial ischemia-reperfusion injury in hypercholesterolemic rat. Cell Biochem Biophys. 2014 Nov;70(2):1017-22. doi: 10.1007/s12013-014-0012-7. PubMed PMID: 24840224.
5. Ren Y, Deng L, Cai Y, Lv Y, Jia D. The protective effect of Na+/Ca2+ exchange blocker kb-r7943 on myocardial ischemia-reperfusion injury in hypercholesterolemic rat. Cell Biochem Biophys. 2014 Nov;70(2):1017-22. doi: 10.1007/s12013-014-0012-7. PubMed PMID: 24840224.

Products are for research use only. Not for human use.