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Home / Biochemicals / Small Molecules

NS-1643

SKU : BHB21300230

An Opener of KV11.1 and KCNQ2 K+ Channels

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Alomone Labs

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Mfr.No.	N-115, N-115_10 mg, N-115_50 mg
Description	NS-1643 (#N-115) is a highly pure, synthetic, and biologically active compound.
Molecular Formula	C15H10F6N2O3.
Background	The KV11.1 (hERG, ERG1, erg1) channel is a member of the ether-a-go-go (EAG) subfamily of voltage-dependent K+ channels that includes the related proteins KV11.2 and KV11.3 (erg2 and erg3). The KV11.1 current is characterized by strong inward rectification with slow activation and very rapid inactivation kinetics. The channel is expressed in the brain and heart (where it underlies the IKr current) and has a central role in mediating repolarization of action potentials1,2.Mutations in the KV11.1 channel cause inherited long QT syndrome (LQTS) or abnormalities in the repolarization of the heart that are associated with life-threatening arrhythmias and sudden death. All the identified KV11.1 mutations produce loss of function of the channel via several cellular mechanisms ranging from alterations of gating properties, channel permeability/selectivity and intracellular channel trafficking that decreases the number of channels that reach the cell membrane1,2.Lately, drug-induced forms of LQTS have been reported for a wide range of non-cardiac drugs including antihistamines, psychoactive agents and antimicrobials. All these drugs potently block the KV11.1 channel as an unintended side effect, prompting regulatory drug agencies to issue recommendations for the testing of new drugs for their potential KV11.1 blocking effect.In addition, KV11.1 expression was found to be upregulated in several tumor cell lines of different histogenesis suggesting that it confers the cells some advantage in cell proliferation. Indeed, in several studies it has been shown that inhibition of the KV11.1 current leads to a decrease in tumor cell proliferation3.NS-1643 is a potent and selective KV11.1 channel modulator (enhancer)4,5. In Xenopus oocytes and in HEK-293 cells, NS-1643 increased both steady-state and tail current at all voltages. The EC50 value for hERG channel activation was 10.5 uM - 20 uM4,5. In guinea pig cardiomyocytes, application of 10 uM NS-1643 activated IKr and significantly decreased the action potential duration to 65% of the control values4. Accordingly, NS-1643 reversed acquired LQTS and Torsades de Pointes (TdP) in rabbits, caused by bradycardiac remodelling and hERG-blocking drugs6.NS-1643 inhibited smooth muscle from bovine epididymal duct contractions with EC50 values of 8 uM7. NS-1643 also activates the ERG2 channel (KV11.2) with an apparent EC50 of 11 uM as measured in Xenopus oocytes8. NS-1643 was also found to potentiate epilepsy-associated KCNQ2 channels with an EC50 of 2.44 uM9. It has no effect on cardiac KCNQ1.
Shipping	Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored at -20°C
Concentration	1-100 uM.
Reconstitution	Centrifuge the vial before adding solvent (10,000 x g for 5 minutes) to spin down all the powder to the bottom of the vial. The lyophilized product may be difficult to visualize. Add solvent directly to the centrifuged vial. Tap the vial to aid in dissolving the lyophilized product. Tilt and gently roll the liquid over the walls of the vial. Avoid vigorous vortexing. Light vortexing for up to 3 seconds is acceptable if needed. For long-term storage in solution, we recommend preparing a stock solution by dissolving the product in sterile water at a concentration of at least 0.1 mg/mL. Divide the stock solution into small aliquots and store at -20°C. Before use, thaw the relevant vial(s) and dilute to the desired working concentration in your working buffer. It is recommended to prepare fresh solutions in working buffers just before use. Repeat freeze-thawing may result in loss of activity
Cas Number	448895-37-2
Molecular Weight	380.2
Solubility	DMSO. Centrifuge all product preparations before use (10000 x g 5 min).
Target	KV11.1, KCNQ2 K+ channels
Source	Synthetic
Activity	NS-1643 is a potent and selective KV11.1 (hERG, ERG1, erg1) channel modulator (enhancer)1. NS-1643 was effective in eliciting and enhancing KV11.1 channels in Xenopus oocytes with apparent EC50 of 20 uM1. NS-1643 inhibited smooth muscle from bovine epididymal duct contractions with EC50 values of 8 uM2. It also potentiates KCNQ2 but not KCNQ1 channels3.
Country Of Origin	Israel/IL
UNSPSC Code	41116134
Application	FC- Flow cytometry, IFC- Indirect flow cytometry, IHC- Immunohistochemistry,LCI- Live cell imaging, Calcium imaging assay,Cell survival assay, Electrophysiology, Neurite outgrowth assay
Lead Time	1-2 Business Days
Notes	Bioassay Tested: Yes Chemical Name: N,N'-Bis(2-hydroxy-5-(trifluoromethyl)phenyl)urea.

Purity	>95%
Form	Lyophilized powder.
Storage	Storage After Reconstitution: The reconstituted solution can be stored at 4°C for up to 1 week. For longer periods (up to 6 months), small aliquots should be stored at -20°C. We do not recommend storing the product in working solutions for longer than a few days. Avoid multiple freeze-thaw cycles. Storage of solutions: Up to four weeks at 4°C or three months at -20°C.

Product Manual	SDS

Reference	Curran, M.E. et al. (1995) Cell 80, 795. Sanguinetti, M.C. et al. (1995) Cell 81, 299. Pardo, L.A. et al. (2004) Physiology 19, 285. Hansen, R.S. et al. (2006) Mol. Pharmacol. 69, 266. Xu, X. et al. (2008) Mol. Pharmacol. 73, 1709. Diness, T.G. et al. (2008) Cardiovas. Res. 79, 61. Mewe, M. et al. (2008) Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R895. Elmedyb, P. et al. (2007) Neuropharmacology 53, 283. Li, P. et al. (2014) J. Pharmacol. Exp. Ther. 351, 596. Xu, X. et al. (2008) Mol. Pharmacol. 73, 1709. Mewe, M. et al. (2008) Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R895. Li, P. et al. (2014) J. Pharmacol. Exp. Ther. 351, 596.

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Combination SKU	Supplier No.	Size	Your price	Quantity
BHB21300230-1	N-115_10 mg	10 mg	$103		Add to Cart
BHB21300230-2	N-115_50 mg	50 mg	$401		Add to Cart

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