JNJ303 | CAS#878489-28-2 | Kv7.1/KCNE1 channel inhibitor

MedKoo Cat#: 561798 | Name: JNJ303

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Description:

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

JNJ303 is a specific inhibitor of heteromeric Kv7.1/KCNE1 channel complexes in a concentration- and time-dependent manner.

Chemical Structure

JNJ303

CAS#878489-28-2

Theoretical Analysis

MedKoo Cat#: 561798

Name: JNJ303

CAS#: 878489-28-2

Chemical Formula: C21H29ClN2O4S

Exact Mass: 440.1537

Molecular Weight: 440.98

Elemental Analysis: C, 57.20; H, 6.63; Cl, 8.04; N, 6.35; O, 14.51; S, 7.27

Price and Availability

Size	Price	Availability
10mg	USD 250.00	2 Weeks
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks

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Related CAS #

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Synonym

JNJ303; JNJ-303; JNJ 303; AC-1; AC 1; AC1;

IUPAC/Chemical Name

2-(4-Chloro-phenoxy)-N-(5-methanesulfonylamino-adamantan-2-yl)-2-methyl-propionamide

InChi Key

OSGIRCJRKSAODN-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H29ClN2O4S/c1-20(2,28-17-6-4-16(22)5-7-17)19(25)23-18-14-8-13-9-15(18)12-21(10-13,11-14)24-29(3,26)27/h4-7,13-15,18,24H,8-12H2,1-3H3,(H,23,25)

SMILES Code

CC(C)(OC1=CC=C(Cl)C=C1)C(NC2C3CC4CC(C3)(NS(=O)(C)=O)CC2C4)=O

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:

JNJ 303 is a potent IKs blocker with an IC50 value of 64 nM.

In vitro activity:

To do this, JNJ303 was administered to cells pre-treated with E4031. Fig. 5A shows representative FP recordings in CPC-iPSC-CMs at baseline and after E4031 administration, followed by JNJ303. E4031 prolonged cFP duration, and JNJ303 enhanced this effect. Reference: Biochim Biophys Acta Mol Cell Res. 2020 Mar;1867(3):118538. https://pubmed.ncbi.nlm.nih.gov/31472168/

In vivo activity:

Repolarization parameters were significantly altered by JNJ303, as presented by a prolonged QT, QTc, and JTc interval (Table 1). The prolongation of the QT and QTc interval by JNJ303 was similar to dofetilide (Table 1, Suppl. Table 1). Finally, TdP arrhythmias were induced in 4/10 dogs during the anesthesia washout period and the AS increased from 1.1 ± 0.3 to 9.2 ± 11.2. Reference: Eur J Pharmacol. 2022 Oct 15;932:175218. https://pubmed.ncbi.nlm.nih.gov/36007604/

	Solvent	mg/mL	mM
Solubility
	DMF	1.0	2.27
	DMSO	40.6	92.14

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 440.98 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. Pianezzi E, Altomare C, Bolis S, Balbi C, Torre T, Rinaldi A, Camici GG, Barile L, Vassalli G. Role of somatic cell sources in the maturation degree of human induced pluripotent stem cell-derived cardiomyocytes. Biochim Biophys Acta Mol Cell Res. 2020 Mar;1867(3):118538. doi: 10.1016/j.bbamcr.2019.118538. Epub 2019 Aug 28. PMID: 31472168. 2. Altomare C, Pianezzi E, Cervio E, Bolis S, Biemmi V, Benzoni P, Camici GG, Moccetti T, Barile L, Vassalli G. Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade. Europace. 2016 Dec;18(suppl 4):iv67-iv76. doi: 10.1093/europace/euw352. PMID: 28011833. 3. van Bavel JJA, Beekman HDM, van Weperen VYH, van der Linde HJ, van der Heyden MAG, Vos MA. IKs inhibitor JNJ303 prolongs the QT interval and perpetuates arrhythmia when combined with enhanced inotropy in the CAVB dog. Eur J Pharmacol. 2022 Oct 15;932:175218. doi: 10.1016/j.ejphar.2022.175218. Epub 2022 Aug 22. PMID: 36007604.

In vitro protocol:

In vivo protocol:

1. van Bavel JJA, Beekman HDM, van Weperen VYH, van der Linde HJ, van der Heyden MAG, Vos MA. IKs inhibitor JNJ303 prolongs the QT interval and perpetuates arrhythmia when combined with enhanced inotropy in the CAVB dog. Eur J Pharmacol. 2022 Oct 15;932:175218. doi: 10.1016/j.ejphar.2022.175218. Epub 2022 Aug 22. PMID: 36007604.

1: Altomare C, Pianezzi E, Cervio E, Bolis S, Biemmi V, Benzoni P, Camici GG, Moccetti T, Barile L, Vassalli G. Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade. Europace. 2016 Dec;18(suppl 4):iv67-iv76. doi: 10.1093/europace/euw352. PubMed PMID: 28011833. 2: Wrobel E, Rothenberg I, Krisp C, Hundt F, Fraenzel B, Eckey K, Linders JT, Gallacher DJ, Towart R, Pott L, Pusch M, Yang T, Roden DM, Kurata HT, Schulze-Bahr E, Strutz-Seebohm N, Wolters D, Seebohm G. KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting. Nat Commun. 2016 Oct 12;7:12795. doi: 10.1038/ncomms12795. PubMed PMID: 27731317; PubMed Central PMCID: PMC5064022. 3: Kuusela J, Kim J, Räsänen E, Aalto-Setälä K. The Effects of Pharmacological Compounds on Beat Rate Variations in Human Long QT-Syndrome Cardiomyocytes. Stem Cell Rev. 2016 Dec;12(6):698-707. PubMed PMID: 27646833; PubMed Central PMCID: PMC5106508. 4: Zhang X, Guo L, Zeng H, White SL, Furniss M, Balasubramanian B, Lis E, Lagrutta A, Sannajust F, Zhao LL, Xi B, Wang X, Davis M, Abassi YA. Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment. J Pharmacol Toxicol Methods. 2016 Sep-Oct;81:201-16. doi: 10.1016/j.vascn.2016.06.004. Epub 2016 Jun 7. PubMed PMID: 27282640. 5: Braam SR, Tertoolen L, Casini S, Matsa E, Lu HR, Teisman A, Passier R, Denning C, Gallacher DJ, Towart R, Mummery CL. Repolarization reserve determines drug responses in human pluripotent stem cell derived cardiomyocytes. Stem Cell Res. 2013 Jan;10(1):48-56. doi: 10.1016/j.scr.2012.08.007. Epub 2012 Sep 7. PubMed PMID: 23089628. 6: Guns PJ, Johnson DM, Weltens E, Lissens J. Negative electro-mechanical windows are required for drug-induced Torsades de Pointes in the anesthetized guinea pig. J Pharmacol Toxicol Methods. 2012 Sep;66(2):125-34. doi: 10.1016/j.vascn.2012.03.007. Epub 2012 Apr 9. PubMed PMID: 22516473.