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SEA0400

Catalog No.GC11517

A selective inhibitor of the Na+/Ca2+ exchanger

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SEA0400 Chemical Structure

Cas No.: 223104-29-8

Size Price Stock Qty
10mM (in 1mL DMSO)
$89.00
In stock
5mg
$115.00
In stock
10mg
$209.00
In stock
50mg
$508.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment: [1]

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)

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.

Reaction Conditions

IC50: 33 nM (neurons), 5.0 nM (astrocytes) and 8.3 nM (microglia). 10 min

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]

Animal models

Guinea Pigs

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.

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.

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.

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.

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.

Chemical Properties

Cas No. 223104-29-8 SDF
Chemical Name 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
Formula C21H19F2NO3 M.Wt 371.38
Solubility ≥ 18.569 mg/mL in DMSO, ≥ 46.4 mg/mL in EtOH with ultrasonic 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.

Complete Stock Solution Preparation Table

Prepare stock solution
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
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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