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JNJ 303
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
JNJ 303图片
CAS NO:878489-28-2
包装与价格:
包装价格(元)
10mg电议
50mg电议

产品介绍
JNJ 303 是一种有效的 IKs 阻断剂,IC50 值为 64 nM。
Cas No.878489-28-2
化学名2-(4-chlorophenoxy)-2-methyl-N-((1R,2s,3S,5s,7s)-5-(methylsulfonamido)adamantan-2-yl)propanamide
Canonical SMILESClC1=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
分子式C21H29ClN2O4S
分子量440.98
溶解度<11.02mg/ml in DMSO
储存条件Store at -20℃
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

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.