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Chemical Structure| 223104-29-8 Chemical Structure| 223104-29-8

Structure of SEA0400
CAS No.: 223104-29-8

Chemical Structure| 223104-29-8

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SEA0400 is a novel and selective inhibitor of the Na+-Ca2+ exchanger (NCX), inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia with IC50s ranging from 5 to 33 nM.

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Product Details of SEA0400

CAS No. :223104-29-8
Formula : C21H19F2NO3
M.W : 371.38
SMILES Code : NC1=CC(OCC)=CC=C1OC2=CC=C(OCC3=CC(F)=CC=C3F)C=C2
MDL No. :MFCD07772188
InChI Key :YSUBLPUJDOWYDP-UHFFFAOYSA-N
Pubchem ID :644100

Safety of SEA0400

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P264-P270-P301+P312-P330

Isoform Comparison

Biological Activity

Target
  • Calcium Channel

    NCX, IC50:33 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
rat microglia 0.3–1.0 µM 12 hours SEA0400 attenuated SNP-induced apoptosis via suppression of the ER stress in cultured microglia. PMC1576047
cardiomyocytes 1 μM 15 minutes SEA0400 prevented the lengthening of action potential induced by artemether PMC7484510
platelets 2 μM 3 minutes SEA0400 reduced the collagen-induced increase in [Ca2+]i PMC3312489
HEK293T cells 10 μM 30 minutes To evaluate the inhibitory effect of SEA0400 on NCX1.3 activity, results showed that SEA0400 significantly blocked the reverse mode activity of NCX1.3. PMC10897212
guinea-pig ventricular myocytes 1 µM SEA0400 significantly inhibited the NCX current and had no significant effect on Na+, Ca2+, and K+ channels PMC1573238
Canine ventricular myocytes 1 μM SEA0400 significantly inhibited both reverse and forward mode activities of NCX, but did not influence APD, CaT, or cell shortening. PMC4290709
Pak1−/− atrial myocytes 1 µM Inhibited NCX activity, reduced spontaneous Ca2+ transients PMC7017889
rat ventricular cardiomyocytes 0.1, 0.3, 1.0 µM SEA0400 inhibited INa/Ca and exerted a positive inotropic effect in rat cardiomyocytes PMC2438973
rabbit ventricular cardiomyocytes 0.1, 0.3, 1.0 µM SEA0400 inhibited INa/Ca but did not significantly affect contractility in rabbit cardiomyocytes PMC2438973

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
rats and rabbits isolated Langendorff-perfused hearts perfusion 0.1, 0.3, 1.0 µM single administration SEA0400 exerted a concentration-dependent positive inotropic effect in rat hearts but had no significant effect in rabbit hearts PMC2438973
Mouse Neonatal mouse ventricular myocardium 10 µM Not specified SEA0400 had no effect on the α-adrenoceptor-mediated positive inotropy PMC9964142

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.46mL

2.69mL

1.35mL

26.93mL

5.39mL

2.69mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Nashida T, Takuma K, et al. 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.

[2]Matsuda T, Arakawa N, 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. J Pharmacol Exp Ther. 2001 Jul;298(1):249-56.

[3]Matsuda T, Arakawa N, Takuma K, Kishida Y, Kawasaki Y, Sakaue M, Takahashi K, Takahashi T, Suzuki T, Ota T, Hamano-Takahashi A, Onishi M, Tanaka Y, Kameo K, Baba A. SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. J Pharmacol Exp Ther. 2001 Jul;298(1):249-56

[4]Nagano T, Osakada M, Ago Y, Koyama Y, Baba A, Maeda S, Takemura M, Matsuda T. SEA0400, a specific inhibitor of the Na+-Ca2+ exchanger, attenuates sodium nitroprusside-induced apoptosis in cultured rat microglia. Br J Pharmacol. 2005 Mar;144(5):669-79

[5]Ago Y, Kawasaki T, Nashida T, Ota Y, Cong Y, Kitamoto M, Takahashi T, Takuma K, Matsuda T. SEA0400, a specific Na+/Ca2+ exchange inhibitor, prevents dopaminergic neurotoxicity in an MPTP mouse model of Parkinson's disease. Neuropharmacology. 2011 Dec;61(8):1441-51

[6]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

 

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