JNJ 303 |
| Catalog No.GC11550 |
JNJ 303 est un puissant bloqueur d'IK avec une valeur IC50 de 64 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 878489-28-2
Sample solution is provided at 25 µL, 10mM.
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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.
| Cas No. | 878489-28-2 | SDF | |
| Chemical Name | 2-(4-chlorophenoxy)-2-methyl-N-((1R,2s,3S,5s,7s)-5-(methylsulfonamido)adamantan-2-yl)propanamide | ||
| Canonical SMILES | ClC1=CC=C(C=C1)OC(C)(C)C(N[C@@H]([C@@H]2C3)[C@H](C4)C[C@@]3(C[C@H]4C2)NS(=O)(C)=O)=O | ||
| Formula | C21H29ClN2O4S | M.Wt | 440.98 |
| Solubility | <11.02mg/ml in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2677 mL | 11.3384 mL | 22.6768 mL |
| 5 mM | 0.4535 mL | 2.2677 mL | 4.5354 mL |
| 10 mM | 0.2268 mL | 1.1338 mL | 2.2677 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)
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