JNJ 303
目录号 : GC11550
An inhibitor of Kv7.1
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 | |
| 化学名 | 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 | ||
| 分子式 | C21H29ClN2O4S | 分子量 | 440.98 |
| 溶解度 | <11.02mg/ml in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet