NS-1643 | CAS#448895-37-2 | KV11.1 channel activator

NS-1643
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 526648

CAS#: 448895-37-2

Description: NS-1643 is a Human ether-a-go-go related gene (hERG) KV11.1 channel activator (EC50 = 10.5 μM). NS1643 increased both steady-state and tail current at all voltages tested. The EC(50) value for HERG channel activation was 10.5 microM. HERG channel activation by small molecules such as NS1643 increases the repolarization reserve and presents an interesting new antiarrhythmic approach.

Chemical Structure

NS-1643

CAS# 448895-37-2

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526648
Name: NS-1643
CAS#: 448895-37-2
Chemical Formula: C15H10F6N2O3
Exact Mass: 380.06
Molecular Weight: 380.246
Elemental Analysis: C, 47.38; H, 2.65; F, 29.98; N, 7.37; O, 12.62

Price and Availability

Size	Price	Availability
50mg	USD 250	2 Weeks
100mg	USD 450
200mg	USD 750
500mg	USD 1650	2 Weeks
1g	USD 2450	2 Weeks
2g	USD 4250	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: NS-1643; NS 1643; NS1643.

IUPAC/Chemical Name: 1,3-bis(2-hydroxy-5-(trifluoromethyl)phenyl)urea

InChi Key: NJFVQMRYJZHGME-UHFFFAOYSA-N

InChi Code: InChI=1S/C15H10F6N2O3/c16-14(17,18)7-1-3-11(24)9(5-7)22-13(26)23-10-6-8(15(19,20)21)2-4-12(10)25/h1-6,24-25H,(H2,22,23,26)

SMILES Code: O=C(NC1=CC(C(F)(F)F)=CC=C1O)NC2=CC(C(F)(F)F)=CC=C2O

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, not in water

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:

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Biological target:	NS1643 is a partial agonist of human ether-a-go-go-related gene (hERG) K+ channels with an EC50 of 10.5 μM.
In vitro activity:	1,3-Bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is a newly discovered activator of human ether-a-go-go-related gene (hERG) K(+) channels. Here, this study characterizes the effects of this compound on cloned hERG channels heterologously expressed in Xenopus laevis oocytes. When assessed with 2-s depolarizations, NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and voltage-dependent manner with an EC(50) of 10.4 microM at -10 mV. NS1643 shifted the voltage dependence of inactivation by +21 mV at 10 microM and +35 mV at 30 microM, but it did not alter the voltage dependence of activation of hERG channels. Reference: Mol Pharmacol. 2006 Feb;69(2):658-65. https://pubmed.ncbi.nlm.nih.gov/16284303/
In vivo activity:	In order to examine whether stimulation of Kv11.1 channel activity would inhibit BC growth and metastasis in vivo, this study established human-derived TNBC xenograft tumors using MDA-MB-231 BC cells in NOD-scid IL2Rγnull (NSG) mice. As previously observed in nude mice, NS1643-treated NSG mice exhibited a persistent and significant reduction of tumor growth throughout the study compared with control mice. (Fig. 1a). When visible, metastatic liver tumors in the NS1643-treated group were significantly smaller than those in the control group (Fig. 1c). Reference: Cell Death Dis. 2019 Feb 21;10(3):180. https://pubmed.ncbi.nlm.nih.gov/30792401/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	25.0	65.75
	DMSO	52.6	138.40
	DMSO:PBS (pH 7.2) (1:3)	0.3	0.66
	Ethanol	41.3	108.72

Preparing Stock Solutions

The following data is based on the product molecular weight 380.25 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:	1. Casis O, Olesen SP, Sanguinetti MC. Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol Pharmacol. 2006 Feb;69(2):658-65. doi: 10.1124/mol.105.019943. Epub 2005 Nov 11. PMID: 16284303. 2. Hansen RS, Diness TG, Christ T, Demnitz J, Ravens U, Olesen SP, Grunnet M. Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643). Mol Pharmacol. 2006 Jan;69(1):266-77. doi: 10.1124/mol.105.015859. Epub 2005 Oct 11. PMID: 16219910. 3. Breuer EK, Fukushiro-Lopes D, Dalheim A, Burnette M, Zartman J, Kaja S, Wells C, Campo L, Curtis KJ, Romero-Moreno R, Littlepage LE, Niebur GL, Hoskins K, Nishimura MI, Gentile S. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death Dis. 2019 Feb 21;10(3):180. doi: 10.1038/s41419-019-1429-0. PMID: 30792401; PMCID: PMC6385342.
In vitro protocol:	1. Casis O, Olesen SP, Sanguinetti MC. Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol Pharmacol. 2006 Feb;69(2):658-65. doi: 10.1124/mol.105.019943. Epub 2005 Nov 11. PMID: 16284303. 2. Hansen RS, Diness TG, Christ T, Demnitz J, Ravens U, Olesen SP, Grunnet M. Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643). Mol Pharmacol. 2006 Jan;69(1):266-77. doi: 10.1124/mol.105.015859. Epub 2005 Oct 11. PMID: 16219910.
In vivo protocol:	1. Breuer EK, Fukushiro-Lopes D, Dalheim A, Burnette M, Zartman J, Kaja S, Wells C, Campo L, Curtis KJ, Romero-Moreno R, Littlepage LE, Niebur GL, Hoskins K, Nishimura MI, Gentile S. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death Dis. 2019 Feb 21;10(3):180. doi: 10.1038/s41419-019-1429-0. PMID: 30792401; PMCID: PMC6385342.

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1: Perissinotti LL, Guo J, De Biase PM, Clancy CE, Duff HJ, Noskov SY. Kinetic model for NS1643 drug activation of WT and L529I variants of Kv11.1 (hERG1) potassium channel. Biophys J. 2015 Mar 24;108(6):1414-24. doi: 10.1016/j.bpj.2014.12.056. PubMed PMID: 25809254; PubMed Central PMCID: PMC4375712.

2: Guo J, Cheng YM, Lees-Miller JP, Perissinotti LL, Claydon TW, Hull CM, Thouta S, Roach DE, Durdagi S, Noskov SY, Duff HJ. NS1643 interacts around L529 of hERG to alter voltage sensor movement on the path to activation. Biophys J. 2015 Mar 24;108(6):1400-13. doi: 10.1016/j.bpj.2014.12.055. PubMed PMID: 25809253; PubMed Central PMCID: PMC4375528.

3: Li P, Chen X, Zhang Q, Zheng Y, Jiang H, Yang H, Gao Z. The human ether-a-go-go-related gene activator NS1643 enhances epilepsy-associated KCNQ channels. J Pharmacol Exp Ther. 2014 Dec;351(3):596-604. doi: 10.1124/jpet.114.217703. Epub 2014 Sep 17. PubMed PMID: 25232191.

4: Bilet A, Bauer CK. Effects of the small molecule HERG activator NS1643 on Kv11.3 channels. PLoS One. 2012;7(11):e50886. doi: 10.1371/journal.pone.0050886. Epub 2012 Nov 30. PubMed PMID: 23226420; PubMed Central PMCID: PMC3511382.

5: Durdagi S, Guo J, Lees-Miller JP, Noskov SY, Duff HJ. Structure-guided topographic mapping and mutagenesis to elucidate binding sites for the human ether-a-go-go-related gene 1 potassium channel (KCNH2) activator NS1643. J Pharmacol Exp Ther. 2012 Aug;342(2):441-52. doi: 10.1124/jpet.111.189159. Epub 2012 May 9. PubMed PMID: 22573844.

6: Schuster AM, Glassmeier G, Bauer CK. Strong activation of ether-à-go-go-related gene 1 K+ channel isoforms by NS1643 in human embryonic kidney 293 and Chinese hamster ovary cells. Mol Pharmacol. 2011 Nov;80(5):930-42. doi: 10.1124/mol.111.071621. Epub 2011 Aug 19. PubMed PMID: 21856740.

7: Grunnet M, Abbruzzese J, Sachse FB, Sanguinetti MC. Molecular determinants of human ether-à-go-go-related gene 1 (hERG1) K+ channel activation by NS1643. Mol Pharmacol. 2011 Jan;79(1):1-9. doi: 10.1124/mol.110.067728. Epub 2010 Sep 27. PubMed PMID: 20876384; PubMed Central PMCID: PMC3014275.

8: Wu SN, Peng H, Chen BS, Wang YJ, Wu PY, Lin MW. Potent activation of large-conductance Ca2+-activated K+ channels by the diphenylurea 1,3-bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in pituitary tumor (GH3) cells. Mol Pharmacol. 2008 Dec;74(6):1696-704. doi: 10.1124/mol.108.049106. Epub 2008 Sep 22. PubMed PMID: 18809671.

9: Peitersen T, Grunnet M, Benson AP, Holden AV, Holstein-Rathlou NH, Olesen SP. Computational analysis of the effects of the hERG channel opener NS1643 in a human ventricular cell model. Heart Rhythm. 2008 May;5(5):734-41. doi: 10.1016/j.hrthm.2008.02.026. Epub 2008 Mar 4. PubMed PMID: 18452879.

10: Xu X, Recanatini M, Roberti M, Tseng GN. Probing the binding sites and mechanisms of action of two human ether-a-go-go-related gene channel activators, 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) and 2-[2-(3,4-dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD307243). Mol Pharmacol. 2008 Jun;73(6):1709-21. doi: 10.1124/mol.108.045591. Epub 2008 Mar 27. Erratum in: Mol Pharmacol. 2008 Jul;74(1):307. PubMed PMID: 18372399; PubMed Central PMCID: PMC3888322.

11: Elmedyb P, Olesen SP, Grunnet M. Activation of ERG2 potassium channels by the diphenylurea NS1643. Neuropharmacology. 2007 Aug;53(2):283-94. Epub 2007 May 21. PubMed PMID: 17610913.

12: Hansen RS, Diness TG, Christ T, Demnitz J, Ravens U, Olesen SP, Grunnet M. Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643). Mol Pharmacol. 2006 Jan;69(1):266-77. Epub 2005 Oct 11. PubMed PMID: 16219910.

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