SEA0400
(Synonyms: 2-[4-[(2,5-二氟苯基)甲氧基]苯氧基]-5-乙氧基苯胺,SEA 0400;SEA-0400) 目录号 : GC11517
A selective inhibitor of the Na+/Ca2+ exchanger
Cas No.:223104-29-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment: [1] | |
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Cell lines |
cortical neurons (dissociated from 18-day rat fetuses), astrocytes (isolated from cerebral cortices of 1-day-old Wistar rats) and microglia (obtained from cerebral cortices of 1-day-old Wistar rats) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
IC50: 33 nM (neurons), 5.0 nM (astrocytes) and 8.3 nM (microglia). 10 min |
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Applications |
SEA040 is a most potent and selective inhibitor of Na+-Ca2+ exchanger (NCX). It inhibited the Na+-dependent 45Ca2+ uptake with IC50 values of 33 nM (neurons), 5.0 nM (astrocytes) and 8.3 nM (microglia). |
| Animal experiment : [2] | |
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Animal models |
Guinea Pigs |
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Dosage form |
Guinea Pigs were anesthetized with sodium pentobarbital (50 mg/kg i.p.). After 15 min of stabilization, SEA0400 were administered at doses of 1–10 mg/kg (each animal received only one dose) as i.v. bolus injection through the jugular vein. Five minutes later, 25 μg/kg of aconitine was injected to induce ventricular arrhythmias. |
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Applications |
SEA0400 showed no significant changes at dose of 10 mg/kg. The duration of normal sinus rhythm, PVC, narrow QRS VT and wide QRS VT were 21.5, 4.3, 17.3 and 16.8 min, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Matsuda T, Arakawa N, Takuma K, et al. SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. Journal of Pharmacology and Experimental Therapeutics, 2001, 298(1): 249-256. [2] Amran M S, Hashimoto K, Homma N. Effects of sodium-calcium exchange inhibitors, KB-R7943 and SEA0400, on aconitine-induced arrhythmias in guinea pigs in vivo, in vitro, and in computer simulation studies. Journal of Pharmacology and Experimental Therapeutics, 2004, 310(1): 83-89. |
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SEA0400 is a potent and selective inhibitor of Na+-Ca2+ exchanger (NCX) with IC50 values of 5 to 33 nM in cultured neurons, microglia and astrocytes [1].
The Na+-Ca2+ exchanger is an anti-porter that pumps Ca2+ out of the cells and keeps the low concentration of Ca2+ inside cells through exchanging the Na+ and Ca2+. In the reperfusion injury, the reverse mode NCX is activated, inducing the paradoxical Ca2+ influx and subsequently causing the generation of free radicals, leucotriene and thromboxane. Many existed drugs target NCX treated for reperfusion injury are reported of lacking selectivity or cell- permeability while SEA0400 is reported to be the most selective and potent NCX inhibitor [1].
SEA0400 was screened out of a chemical library designed for inhibition of NCX in cultured astrocytes and isolated cardiac sarcolemmal vesicles. It showed potent inhibitory effects on Na+-dependent Ca2+ uptake in cultured microglia, astrocytes and neurons with IC50 values of 8.3, 5 and 33 nM, respectively. The activity of SEA0400 was more than 100-fold higher than that of KB-R7943. SEA0400 was also proved to be selective against NCX over other ion fluxes since it displayed no significant effect on SOCE even at the concentration up to 3 μM. Besides that, SEA0400 had no effect on a serious of similar ion channels or ion transporters such as Ca2+-ATPase, Na+, K+-ATPase and K+ channel. Moreover, SEA0400 was found to suppress the Ca2+ influx-induced apoptosis in astrocytes [1].
In a rat model of cerebral ischemia, injection of SEA0400 at dose of 3 mg/kg resulted in decreased infarct volume in both striatum and cerebral cortex. In a rabbit model of Langendorff-perfused 1-month myocardial infarction, SEA0400 administration inhibited the pacing-induced ventricular premature beats and displayed proarrhythmic activity through enhancing spatially discordant alternans (SDA) and steepening Action potential duration (APD) restitution [1 and 2].
References:
[1] Matsuda T, Arakawa N, Takuma K, et al. SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. Journal of Pharmacology and Experimental Therapeutics, 2001, 298(1): 249-256.
[2] CHOU C C, CHANG P O C, WEN M S, et al. Effects of SEA0400 on Arrhythmogenicity in a Langendorff-Perfused 1-Month Myocardial Infarction Rabbit Model Pacing and Clinical Electrophysiology, 2013, 36(5): 596-606.
| Cas No. | 223104-29-8 | SDF | |
| 别名 | 2-[4-[(2,5-二氟苯基)甲氧基]苯氧基]-5-乙氧基苯胺,SEA 0400;SEA-0400 | ||
| 化学名 | 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline | ||
| Canonical SMILES | CCOC1=CC(=C(C=C1)OC2=CC=C(C=C2)OCC3=C(C=CC(=C3)F)F)N | ||
| 分子式 | C21H19F2NO3 | 分子量 | 371.38 |
| 溶解度 | ≥ 18.569 mg/mL in DMSO, ≥ 46.4 mg/mL in EtOH with ultrasonic | 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 | 2.6927 mL | 13.4633 mL | 26.9266 mL |
| 5 mM | 0.5385 mL | 2.6927 mL | 5.3853 mL |
| 10 mM | 0.2693 mL | 1.3463 mL | 2.6927 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。