JNJ 303

potent blocker of the slow component of delayed rectifier potassium current (IKs) CAS# 878489-28-2

JNJ 303

Catalog No. BCC7806----Order now to get a substantial discount!

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Chemical structure

JNJ 303

3D structure

Chemical Properties of JNJ 303

Cas No. 878489-28-2 SDF Download SDF
PubChem ID 11575823 Appearance Powder
Formula C21H29ClN2O4S M.Wt 440.98
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 62.5 mg/mL (141.73 mM; Need ultrasonic)
Chemical Name 2-(4-chlorophenoxy)-N-[(1R,3S)-5-(methanesulfonamido)-2-adamantyl]-2-methylpropanamide
SMILES CC(C)(C(=O)NC1C2CC3CC1CC(C3)(C2)NS(=O)(=O)C)OC4=CC=C(C=C4)Cl
Standard InChIKey OSGIRCJRKSAODN-DJASPMHUSA-N
Standard InChI 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)/t13?,14-,15+,18?,21?
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of JNJ 303

DescriptionPotent IKs blocker (IC50 = 64 nM). Displays no effects on other cardiac channels; IC50 values are 3.3, >10, 11.1 and 12.6 μM for INa, ICa, Ito and IKr currents respectively. Prolongs QT and causes unprovoked torsades de pointes (TdP).

JNJ 303 Dilution Calculator

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JNJ 303 Molarity Calculator

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Preparing Stock Solutions of JNJ 303

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.2677 mL 11.3384 mL 22.6768 mL 45.3535 mL 56.6919 mL
5 mM 0.4535 mL 2.2677 mL 4.5354 mL 9.0707 mL 11.3384 mL
10 mM 0.2268 mL 1.1338 mL 2.2677 mL 4.5354 mL 5.6692 mL
50 mM 0.0454 mL 0.2268 mL 0.4535 mL 0.9071 mL 1.1338 mL
100 mM 0.0227 mL 0.1134 mL 0.2268 mL 0.4535 mL 0.5669 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on JNJ 303

JNJ 303 is a potent blocker of the slow component of delayed rectifier potassium current (IKs) [1] with an IC50 value of 0.064 μM [2].

Accompanied by the transient outward current (Ito), IKs channel is a main potassium channel that affects cardiac repolarisation and thus the length of the QT interval [2].

Dofetilide accompanied by JNJ 303 resulted in an additional 80% field potential prolongation. Sotalol administration with JNJ 303 in hPSC-CM resulted in an additional maximum prolongation of field potential (FP) duration of ~25% of cells. JNJ 303 treatment in a patient-derived hiPSC line led to a maximum 30% prolongation, this prolongation is significantly more than that in the control hPSC-CM. JNJ 303 had minor effect on the repolarization of spontaneously beating human pluripotent stem cells (hPSC-CM) [1].

The addition of IKs blockade to IKr blockade gave at least additive QT prolongation and even torsades de pointes (TdP). Treatment with JNJ 303 resulted in spontaneous events of a “pause-dependent” TdP nature in an anaesthetised dog model. Treatment with JNJ 303 made at least two animals die unexpectedly in early pharmacokinetic or pharmacological studies. Compared with other tested sulphonamide analogue in an adrenergic-dependent TdP dog model, JNJ 303 bore a much reduced IKr (hERG, rapidly activating delayed inward rectifier potassium channel) blocking activity with an IC50 value of 12,640 nM and a higher potency on the 11β-hydroxysteroid dehydrogenase-1 (HSD1) [2].

References:
[1].  S. R. Braam, L. Tertoolen, S. Casini, et al. Repolarization reserve determines drug responses in human pluripotent stem cell derived cardiomyocytes. Stem Cell Research, 2013, 10:48-56.
[2].  Rob Towart, Joannes T.M. Linders, An N. Hermans, et al. Blockade of the IKs potassium channel: An overlooked cardiovascular liability in drug safety screening? Journal of Pharmacological and Toxicological Methods, 2009, 60: 1-10.

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Description

JNJ 303 is a potent IKs blocker with an IC50 value of 64 nM. JNJ 303 does not have any effects on other cardiac channels at concentrations of 3.3 μM for INa, Ica, Ito, and IKr. JNJ 303 induces QT-prolongations and causes unprovoked torsades de pointes (TdP).

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