NS3623 | CAS#343630-41-1 | Voltage-gated Potassium Channel Activator

MedKoo Cat#: 532368 | Name: NS3623

Description:

WARNING: This product is for research use only, not for human or veterinary use.

NS3623 is a KV11.1 (hERG) and KV4.3 channel activator. NS3623 activates the IKr and Ito currents and displays antiarrhythmic activity. NS3623 may also act as a partial blocker of KV11.1 channels. NS3623 is suitable for both in vitro and in vivo use.

Chemical Structure

NS3623

CAS#343630-41-1

Theoretical Analysis

MedKoo Cat#: 532368

Name: NS3623

CAS#: 343630-41-1

Chemical Formula: C15H10BrF3N6O

Exact Mass: 426.0052

Molecular Weight: 427.19

Elemental Analysis: C, 42.17; H, 2.36; Br, 18.70; F, 13.34; N, 19.67; O, 3.75

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,250.00	2 Weeks
1g	USD 3,450.00	2 Weeks
2g	USD 5,950.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

NS3623; NS 3623; NS-3623.

IUPAC/Chemical Name

1-[4-bromo-2-(2H-tetrazol-5-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea

InChi Key

JXPULDIATMTIIN-UHFFFAOYSA-N

InChi Code

InChI=1S/C15H10BrF3N6O/c16-9-4-5-12(11(7-9)13-22-24-25-23-13)21-14(26)20-10-3-1-2-8(6-10)15(17,18)19/h1-7H,(H2,20,21,26)(H,22,23,24,25)

SMILES Code

O=C(NC1=CC=CC(C(F)(F)F)=C1)NC2=CC=C(Br)C=C2C3=NNN=N3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

NS 3623 is a KV11.1 (hERG) and KV4.3 channel activator. Activates the IKr and Ito currents and displays antiarrhythmic activity. May also act as a partial blocker of KV11.1 channels. Displays selectivity over the key cardiac potassium channels, KV7.1 (KCNQ1) and KV1.5. Suitable for both in vitro and in vivo use.

In vitro activity:

In vitro, NS3623 reversibly blocked human RBC Cl-conductance (g(Cl)) with an IC(50) value of 210 nmol/L and a maximal block of 95%. In vivo, NS3623 inhibited RBC g(Cl) after oral administration to normal mice (ED(50) = 25 mg/kg). Although g(Cl), at a single dose of 100 mg/kg, was still 70% inhibited 5 hours after dosing, the inhibition disappeared after 24 hours. Repeated administration of 100 mg/kg twice a day for 10 days caused no adverse effects; therefore, this regimen was chosen as the highest dosing for the SAD mice. SAD mice were treated for 3 weeks with 2 daily administrations of 10, 35, and 100 mg/kg NS3623, respectively. The hematocrit increased, and the mean corpuscular hemoglobin concentration decreased in all groups with a concomitant increase in the intracellular cation content. A loss of the densest red cell population was observed in conjunction with a shift from a high proportion of sickled to well-hydrated discoid erythrocytes, with some echinocytes present at the highest dosage. These data indicate feasibility for the potential use of Cl-conductance blockers to treat human sickle cell disease. Reference: Bennekou P, de Franceschi L, Pedersen O, Lian L, Asakura T, Evans G, Brugnara C, Christophersen P. Treatment with NS3623, a novel Cl-conductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease. Blood. 2001 Mar 1;97(5):1451-7. doi: 10.1182/blood.v97.5.1451. PMID: 11222393.

In vivo activity:

The present study was dedicated to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a hERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically induced QT prolongation in both anaesthetized and conscious guinea pigs. Reference: Hansen RS, Olesen SP, Rønn LC, Grunnet M. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig. J Cardiovasc Pharmacol. 2008 Jul;52(1):35-41. doi: 10.1097/FJC.0b013e31817dd013. PMID: 18594476.

	Solvent	mg/mL	mM
Solubility
	Soluble in DMSO	42.7	100.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 427.19 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

Bennekou P, de Franceschi L, Pedersen O, Lian L, Asakura T, Evans G, Brugnara C, Christophersen P. Treatment with NS3623, a novel Cl-conductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease. Blood. 2001 Mar 1;97(5):1451-7. doi: 10.1182/blood.v97.5.1451. PMID: 11222393.

In vitro protocol:

In vivo protocol:

Hansen RS, Olesen SP, Rønn LC, Grunnet M. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig. J Cardiovasc Pharmacol. 2008 Jul;52(1):35-41. doi: 10.1097/FJC.0b013e31817dd013. PMID: 18594476.

1: Calloe K, Di Diego JM, Hansen RS, Nagle SA, Treat JA, Cordeiro JM. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials. Biochem Pharmacol. 2016 May 15;108:36-46. doi: 10.1016/j.bcp.2016.03.015. Epub 2016 Mar 19. PubMed PMID: 27002181. 2: Larsen AP, Olesen SP, Grunnet M, Poelzing S. Pharmacological activation of IKr impairs conduction in guinea pig hearts. J Cardiovasc Electrophysiol. 2010 Aug 1;21(8):923-9. doi: 10.1111/j.1540-8167.2010.01733.x. Epub 2010 Feb 16. PubMed PMID: 20163495. 3: George AL Jr. Restoring repolarization in LQT3. Heart Rhythm. 2009 Jan;6(1):107-8. doi: 10.1016/j.hrthm.2008.10.037. Epub 2008 Oct 29. PubMed PMID: 19121809; PubMed Central PMCID: PMC2631665.