SEA0400
SEA0400 (CAS 223104-29-8) is a selective inhibitor of the sodium-calcium exchanger (NCX), an antiporter responsible for cellular calcium homeostasis by facilitating sodium-calcium ion exchange across membranes. SEA0400 inhibits NCX activity at nanomolar concentrations (IC50 between 5-33 nM in neuronal and glial cell cultures), with substantially higher potency than KB-R7943. By blocking reverse-mode NCX function during reperfusion scenarios, SEA0400 reduces pathological intracellular calcium influx and downstream pro-inflammatory mediator production. It has demonstrated neuroprotective effects by reducing infarction volumes in rodent cerebral ischemia models, as well as anti-arrhythmic properties in myocardial infarction models.
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.
- 1. Weizhen Li, Emilia Entcheva. "Syncytium cell growth increases IK1 contribution in human iPS-cardiomyocytes." bioRxiv. 2019 December 03.
- 2. 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
- 3. 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
- 4. 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.
- 5. 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 371.38 |
| Cas No. | 223104-29-8 |
| Formula | C21H19F2NO3 |
| Synonyms | SEA 0400;SEA-0400 |
| Solubility | insoluble in H2O; ≥18.57 mg/mL in DMSO; ≥46.4 mg/mL in EtOH with ultrasonic |
| Chemical Name | 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline |
| SDF | Download SDF |
| Canonical SMILES | CCOc(cc1)cc(N)c1Oc(cc1)ccc1OCc(cc(cc1)F)c1F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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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| Description | SEA0400 is a novel and selective inhibitor of the Na+-Ca2+ exchanger (NCX) with IC50 value of 5-33 nM. | |||||
| Targets | Na+-Ca2+ exchanger | |||||
| IC50 | 5-33 nM | |||||
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