SEA0400 | SEA-0400 | CAS#223104-29-8 | Na+/Ca2+ exchanger 1 inhibitor

MedKoo Cat#: 526678 | Name: SEA0400

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SEA0400 is a Na+/Ca2+ exchanger 1 inhibitor. SEA0400 prevents dopaminergic neurotoxicity in an MPTP mouse model of Parkinson's disease. SEA0400 reduces calcium overload induced by ischemia and reperfusion in mouse ventricular myocytes. SEA0400 attenuates sodium nitroprusside-induced apoptosis in cultured rat microglia. SEA0400, preserves cardiac function and high-energy phosphates against ischemia/reperfusion injury.

Chemical Structure

SEA0400

CAS#223104-29-8

Theoretical Analysis

MedKoo Cat#: 526678

Name: SEA0400

CAS#: 223104-29-8

Chemical Formula: C21H19F2NO3

Exact Mass: 371.1333

Molecular Weight: 371.38

Elemental Analysis: C, 67.92; H, 5.16; F, 10.23; N, 3.77; O, 12.92

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

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Synonym

SEA0400; SEA-0400; SEA 0400.

IUPAC/Chemical Name

2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline

InChi Key

YSUBLPUJDOWYDP-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H19F2NO3/c1-2-25-18-8-10-21(20(24)12-18)27-17-6-4-16(5-7-17)26-13-14-11-15(22)3-9-19(14)23/h3-12H,2,13,24H2,1H3

SMILES Code

NC1=CC(OCC)=CC=C1OC2=CC=C(OCC3=CC(F)=CC=C3F)C=C2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, DMF, and ethanol

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SEA0400 is a selective inhibitor of the Na+/Ca2+ exchanger (IC50s = 5, 8.3, and 33 nM for inhibiting Na+-dependent Ca2+ uptake in rat astrocyte, microglia, and cortical neuron cell lines, respectively).

In vitro activity:

SEA0400 exhibits renoprotective effects in a hypoxic injury model using porcine renal tubular cells expressing wild-type NCX1 but not SEA0400-insensitive mutants. SEA0400 demonstrates preferential inhibition of (45)Ca(2+) uptake by NCX1 compared to NCX2, NCX3, and NCKX2 in NCX-transfected fibroblasts. Reference: J Biol Chem. 2004 Feb 27;279(9):7544-53. https://pubmed.ncbi.nlm.nih.gov/14660663/

In vivo activity:

The results of this study suggest that SEA0400's antiarrhythmic effects on IKr blocker-induced TdP may be multifaceted, depending on the severity of proarrhythmogenic conditions, distinguishing it from the effects of verapamil. SEA0400 has the potential to inhibit low-dose nifekalant-induced TdP by suppressing the MAP-prolonging action of nifekalant. In animals treated with high-dose nifekalant, SEA0400 inhibited TdP without affecting the MAP-prolonging action of nifekalant. Reference: Biol Pharm Bull. 2023;46(8):1120-1127. https://pubmed.ncbi.nlm.nih.gov/37532563/

	Solvent	mg/mL	mM
Solubility
	DMF	1.0	2.69
	DMSO	2.0	5.39
	Ethanol	0.3	0.67

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 371.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Nashida T, Takuma K, Fukuda S, Kawasaki T, Takahashi T, Baba A, Ago Y, Matsuda T. The specific Na(+)/Ca(2+) exchange inhibitor SEA0400 prevents nitric oxide-induced cytotoxicity in SH-SY5Y cells. Neurochem Int. 2011 Aug;59(1):51-8. doi: 10.1016/j.neuint.2011.03.026. Epub 2011 Jun 6. PMID: 21672583. 2. Iwamoto T, Kita S, Uehara A, Imanaga I, Matsuda T, Baba A, Katsuragi T. Molecular determinants of Na+/Ca2+ exchange (NCX1) inhibition by SEA0400. J Biol Chem. 2004 Feb 27;279(9):7544-53. doi: 10.1074/jbc.M310491200. Epub 2003 Dec 5. PMID: 14660663. 3. Kawakami S, Takada K, Aimoto M, Nagasawa Y, Kusakabe T, Kato K, Takahara A. The Antiarrhythmic Action of the Na+/Ca2+ Exchanger Inhibitor SEA0400 on Drug-Induced Long QT Syndrome Depends on the Severity of Proarrhythmic Conditions in Anesthetized Atrioventricular Block Rabbits. Biol Pharm Bull. 2023;46(8):1120-1127. doi: 10.1248/bpb.b23-00202. PMID: 37532563. 4. Bögeholz N, Schulte JS, Kaese S, Bauer BK, Pauls P, Dechering DG, Frommeyer G, Goldhaber JI, Kirchhefer U, Eckardt L, Pott C, Müller FU. The Effects of SEA0400 on Ca2+ Transient Amplitude and Proarrhythmia Depend on the Na+/Ca2+ Exchanger Expression Level in Murine Models. Front Pharmacol. 2017 Sep 21;8:649. doi: 10.3389/fphar.2017.00649. PMID: 28983248; PMCID: PMC5613119.

In vitro protocol:

In vivo protocol:

1. Kawakami S, Takada K, Aimoto M, Nagasawa Y, Kusakabe T, Kato K, Takahara A. The Antiarrhythmic Action of the Na+/Ca2+ Exchanger Inhibitor SEA0400 on Drug-Induced Long QT Syndrome Depends on the Severity of Proarrhythmic Conditions in Anesthetized Atrioventricular Block Rabbits. Biol Pharm Bull. 2023;46(8):1120-1127. doi: 10.1248/bpb.b23-00202. PMID: 37532563. 2. Bögeholz N, Schulte JS, Kaese S, Bauer BK, Pauls P, Dechering DG, Frommeyer G, Goldhaber JI, Kirchhefer U, Eckardt L, Pott C, Müller FU. The Effects of SEA0400 on Ca2+ Transient Amplitude and Proarrhythmia Depend on the Na+/Ca2+ Exchanger Expression Level in Murine Models. Front Pharmacol. 2017 Sep 21;8:649. doi: 10.3389/fphar.2017.00649. PMID: 28983248; PMCID: PMC5613119.

1: Wilhelmy B, Gerzanich V, Simard JM, Stokum JA. The NCX1 calcium exchanger is implicated in delayed axotomy after peripheral nerve stretch injury. J Peripher Nerv Syst. 2024 Oct 14. doi: 10.1111/jns.12663. Epub ahead of print. PMID: 39402795. 2: Yarishkin O, Lakk M, Rudzitis CN, Searle JE, Kirdajova D, Križaj D. Resting trabecular meshwork cells experience constitutive cation influx. Vision Res. 2024 Nov;224:108487. doi: 10.1016/j.visres.2024.108487. Epub 2024 Sep 19. PMID: 39303640; PMCID: PMC11552692. 3: Saito T, Suzuki M, Ohba A, Hamaguchi S, Namekata I, Tanaka H. Enhanced Late INa Induces Intracellular Ion Disturbances and Automatic Activity in the Guinea Pig Pulmonary Vein Cardiomyocytes. Int J Mol Sci. 2024 Aug 9;25(16):8688. doi: 10.3390/ijms25168688. PMID: 39201376; PMCID: PMC11354854. 4: Yeste M, Ahmad A, Viñolas E, Recuero S, Bonet S, Pinart E. Inhibition of forward and reverse transport of Ca2+ via Na+/Ca2+ exchangers (NCX) prevents sperm capacitation. Biol Res. 2024 Aug 23;57(1):57. doi: 10.1186/s40659-024-00535-9. PMID: 39175101; PMCID: PMC11342557. 5: Boikov SI, Karelina TV, Sibarov DA, Antonov SM. Selective inhibitor of sodium-calcium exchanger, SEA0400, affects NMDA receptor currents and abolishes their calcium-dependent block by tricyclic antidepressants. Front Pharmacol. 2024 Aug 2;15:1432718. doi: 10.3389/fphar.2024.1432718. PMID: 39156114; PMCID: PMC11327140. 6: Dong Y, Yu Z, Li Y, Huang B, Bai Q, Gao Y, Chen Q, Li N, He L, Zhao Y. Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400. EMBO J. 2024 Jan;43(1):14-31. doi: 10.1038/s44318-023-00013-0. Epub 2023 Dec 15. PMID: 38177313; PMCID: PMC10897212. 7: Kawakami S, Takada K, Aimoto M, Nagasawa Y, Kusakabe T, Kato K, Takahara A. The Antiarrhythmic Action of the Na+/Ca2+ Exchanger Inhibitor SEA0400 on Drug-Induced Long QT Syndrome Depends on the Severity of Proarrhythmic Conditions in Anesthetized Atrioventricular Block Rabbits. Biol Pharm Bull. 2023;46(8):1120-1127. doi: 10.1248/bpb.b23-00202. PMID: 37532563. 8: Takei GL, Ogura Y, Ujihara Y, Toyama F, Hayashi K, Fujita T. Hamster Sperm Possess Functional Na+/Ca2+-Exchanger 1: Its Implication in Hyperactivation. Int J Mol Sci. 2023 May 17;24(10):8905. doi: 10.3390/ijms24108905. PMID: 37240252; PMCID: PMC10219178. 9: Ono N, Horikoshi J, Izawa T, Nishiyama K, Tanaka M, Kuwamura M, Azuma YT. L-arginine-induced pancreatitis aggravated by inhibiting Na+/Ca2+ exchanger 1. J Vet Med Sci. 2023 Jun 13;85(6):657-666. doi: 10.1292/jvms.22-0569. Epub 2023 May 23. PMID: 37100607; PMCID: PMC10315542. 10: Sun HW, Chu XP, Simon RP, Xiong ZG, Leng TD. Inhibition of Acid-Sensing Ion Channels by KB-R7943, a Reverse Na+/Ca2+ Exchanger Inhibitor. Biomolecules. 2023 Mar 10;13(3):507. doi: 10.3390/biom13030507. PMID: 36979442; PMCID: PMC10046550. 11: Hamaguchi S, Morinou I, Shiseki Y, Mikami A, Seki M, Namekata I, Tanaka H. Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation. Int J Mol Sci. 2023 Feb 15;24(4):3926. doi: 10.3390/ijms24043926. PMID: 36835338; PMCID: PMC9964142. 12: Wang HT, Miyairi S, Kitamura M, Iizuka K, Asano Y, Yoshimura T, Kon N. Real time monitoring of cold Ca2+ dependent transcription and its modulation by NCX inhibitors. Sci Rep. 2022 Oct 15;12(1):17325. doi: 10.1038/s41598-022-22166-4. PMID: 36243739; PMCID: PMC9569354. 13: Ballarini E, Malacrida A, Rodriguez-Menendez V, Pozzi E, Canta A, Chiorazzi A, Monza L, Semperboni S, Meregalli C, Carozzi VA, Hashemi M, Nicolini G, Scuteri A, Housley SN, Cavaletti G, Alberti P. Sodium-Calcium Exchanger 2: A Pivotal Role in Oxaliplatin Induced Peripheral Neurotoxicity and Axonal Damage? Int J Mol Sci. 2022 Sep 2;23(17):10063. doi: 10.3390/ijms231710063. PMID: 36077454; PMCID: PMC9456447. 14: Ismaili D, Gurr K, Horváth A, Yuan L, Lemoine MD, Schulz C, Sani J, Petersen J, Reichenspurner H, Kirchhof P, Jespersen T, Eschenhagen T, Hansen A, Koivumäki JT, Christ T. Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue. Cells. 2022 Aug 5;11(15):2424. doi: 10.3390/cells11152424. PMID: 35954268; PMCID: PMC9368200. 15: Namekata I, Jitsukata K, Fukuda A, Odaka R, Hamaguchi S, Tanaka H. Intracellular Ca2+-Mediated Mechanisms for the Pacemaker Depolarization of the Mouse and Guinea Pig Sinus Node Tissue. Biomolecules. 2022 Feb 28;12(3):377. doi: 10.3390/biom12030377. PMID: 35327569; PMCID: PMC8945042. 16: Hamaguchi S, Abe K, Komatsu M, Kainuma J, Namekata I, Tanaka H. Positive Lusitropic Effect of Quercetin on Isolated Ventricular Myocardia from Normal and Streptozotocin-Induced Diabetic Mice. Biol Pharm Bull. 2021;44(12):1894-1897. doi: 10.1248/bpb.b21-00580. PMID: 34853274. 17: Santos-Miranda A, Joviano-Santos JV, Sarmento JO, Costa AD, Soares ATC, Machado FS, Cruz JS, Roman-Campos D. A novel substrate for arrhythmias in Chagas disease. PLoS Negl Trop Dis. 2021 Jun 2;15(6):e0009421. doi: 10.1371/journal.pntd.0009421. PMID: 34077437; PMCID: PMC8172059. 18: Luo HY, Hu XW, Zhang LP, Zeng Y, Guan XW. Functional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage. Sheng Li Xue Bao. 2020 Dec 25;72(6):757-764. PMID: 33349834. 19: Namekata I, Odaka R, Hamazaki S, Nisaka H, Hamaguchi S, Tanaka H. Fluorescence Discrimination of Pharmacological Effects on the Na+-Ca2+ Exchanger and Sarco-Endoplasmic Reticulum Ca2+-ATPase in Mouse Ventricular Cardiomyocytes. Biol Pharm Bull. 2021 Jan 1;44(1):154-157. doi: 10.1248/bpb.b20-00701. Epub 2020 Oct 30. PMID: 33132367. 20: Wolfes J, Ellermann C, Broer N, Rath B, Willy K, Leitz PR, Lange PS, Eckardt L, Frommeyer G. Antiarrhythmic Effect of Ranolazine in Combination with Selective NCX-Inhibition in an Experimental Model of Atrial Fibrillation. Pharmaceuticals (Basel). 2020 Oct 20;13(10):321. doi: 10.3390/ph13100321. PMID: 33092020; PMCID: PMC7589655.