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SEA0400

现货
Catalog No.
A3811
特异性的Na+/Ca2+交换抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,300.00
现货
5mg
¥ 1,650.00
现货
10mg
¥ 2,800.00
现货
50mg
¥ 6,500.00
现货

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Background

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.

文献引用

1. Nie J, Duan Q, et al. "Ranolazine prevents pressure overload-induced cardiac hypertrophy and heart failure by restoring aberrant Na(+) and Ca(2+) handling." J Cell Physiol. 2018 Nov 29. PMID:30488495
2. Halty-deLeon L, Hansson BS, Wicher D. "The Drosophila melanogaster Na(+)/Ca(2+) Exchanger CALX Controls the Ca(2+) Level in Olfactory Sensory Neurons at Rest and After Odorant Receptor Activation." Front Cell Neurosci. 2018 Jul 3;12:186. PMID:30018538
3. Jovana Bojcevski, dipl. Phys. "Calcium-mediated mechanisms of retinal ganglion cell degeneration during autoimmune optic neuritis." Ruperto-Carola University of Heidelberg, Germany. 2017 May 23.
4. Hashad AM, Mazumdar N, et al. "Interplay among distinct Ca(2+) conductances drives Ca(2+) sparks/spontaneous transient outward currents in rat cerebral arteries." J Physiol. 2016 Nov 2. PMID:27805790

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt371.38
Cas No.223104-29-8
FormulaC21H19F2NO3
SynonymsSEA 0400;SEA-0400
Solubility≥18.569 mg/mL in DMSO, ≥46.4 mg/mL in EtOH with ultrasonic, <2.21 mg/mL in H2O
Chemical Name2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline
SDFDownload SDF
Canonical SMILESCCOC1=CC(=C(C=C1)OC2=CC=C(C=C2)OCC3=C(C=CC(=C3)F)F)N
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

皮质神经元(从18天的大鼠胎儿中分离)、星形胶质细胞和小胶质细胞(从1日龄Wistar大鼠的大脑皮层中分离)。

溶解方法

溶于DMSO。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

10 min;IC50:33 nM(神经元)、5.0 nM(星形胶质细胞)和8.3 nM(小胶质细胞)。

应用

SEA040是一种最有效的和选择性的Na+-Ca2+交换体(NCX)抑制剂,抑制Na+依赖的Ca2+吸收,IC50值分别为33 nM(神经元)、5.0 nM(星形胶质细胞)和8.3 nM(小胶质细胞)。

动物实验[2]:

动物模型

豚鼠

剂量

豚鼠用戊巴比妥钠(50 mg/kg;i.p.)麻醉,稳定15 min后,SEA0400以1–10 mg/kg的剂量(每只动物只接受一种剂量)通过颈静脉注射,5 min后,注射25 μg/kg的乌头碱(aconitine),诱发室性心律失常。

应用

SEA0400在10 mg/kg剂量时没有引起显著的变化,正常窦性心律、PVC、窄QRS VT和宽QRS VT的持续时间分别是21.5、4.3、17.3和16.8 min。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

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.

生物活性

描述 SEA0400是一种新型的和选择性的Na+-Ca2+交换体(NCX)抑制剂,IC50值为5-33 nM。
靶点 Na+-Ca2+ exchanger          
IC50 5-33 nM          

质量控制

化学结构

SEA0400

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