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MedKoo Cat#: 530006 | Name: Sipatrigine
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Description:

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

Sipatrigine is a multiple channels blocker potentially for the treatment of stroke. It has been shown to blocks multiple cardiac ion channels, cause triangulation of the ventricular action potential,and could have therapeutic potential for major depression and bipolar depression through antagonism of the two-pore-domain K+ channel TREK-1.

Chemical Structure

Sipatrigine
Sipatrigine
CAS#130800-90-7

Theoretical Analysis

MedKoo Cat#: 530006

Name: Sipatrigine

CAS#: 130800-90-7

Chemical Formula: C15H16Cl3N5

Exact Mass: 371.0471

Molecular Weight: 372.68

Elemental Analysis: C, 48.34; H, 4.33; Cl, 28.54; N, 18.79

Price and Availability

Size Price Availability Quantity
10mg USD 600.00 2 weeks
50mg USD 1,650.00 2 weeks
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Related CAS #
No Data
Synonym
619C; 619C-89; BW-619C-89; BW-619C89; 619 C; 619C 89; BW 619C-89; BW 619C89; 619C; 619C89; BW619C89;
IUPAC/Chemical Name
2-(4-methylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine
InChi Key
PDOCBJADCWMDGL-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H16Cl3N5/c1-22-2-4-23(5-3-22)15-20-8-11(14(19)21-15)10-6-9(16)7-12(17)13(10)18/h6-8H,2-5H2,1H3,(H2,19,20,21)
SMILES Code
NC1=NC(N2CCN(C)CC2)=NC=C1C3=CC(Cl)=CC(Cl)=C3Cl
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 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:
Sipatrigine inhibits neuronal voltage-gated sodium and calcium channels in a voltage-dependent manner. Sipatrigine reduces the neuronal firing frequency and decreases the amplitude of excitatory post-synaptic potentials (EPSPs) in electrically stimulated rat corticostriatal slices (EC50s = 4.5 and 2 µM, respectively). It inhibits veratrine-induced glutamate and aspartate release in rat cerebral cortex slices (IC50s = ~5 µM for both).
In vitro activity:
Sipatrigine exhibited broad-spectrum blocking effects on cation channels in the heart. Sipatrigine modulates cardiac potassium, calcium, and sodium currents, influencing the repolarization of ventricular action potentials. In guinea-pig isolated ventricular myocytes, sipatrigine inhibits delayed rectifier currents (I(Kr) and I(Ks)), inward rectifier current (I(K1)), L-type Ca2+ current (I(Ca,L)), and fast Na+ current (I(Na)). Sipatrigine was a more potent inhibitor of I(Kr) and I(Ks) than I(K1), I(Ca,L), and I(Na). Reference: Clin Exp Pharmacol Physiol. 2005 Dec;32(12):1088-96. https://pubmed.ncbi.nlm.nih.gov/16445575/
In vivo activity:
In the rat subdural hematoma model, 619C89 was highly neuroprotective; its effects may, in part, be mediated by the inhibition of glutamate release from the ischemic cortex underneath the hematoma. Postinjury treatment with 619C89 (30 mg/kg) significantly reduced the volume of hemispheric ischemic damage produced by subdural hematoma. In the 619C89-treated animals, the release of glutamate from the cortex underneath the hematoma was significantly attenuated. Reference: J Neurosurg. 1996 Jul;85(1):104-11. https://pubmed.ncbi.nlm.nih.gov/8683258/
Solvent mg/mL mM comments
Solubility
DMSO 37.3 100.00
Ethanol 9.3 25.00
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 372.68 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.

Recalculate based on batch purity %
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. Walsh Y, Leach M, Veale EL, Mathie A. Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092. Biochem Biophys Rep. 2021 May 19;26:101021. doi: 10.1016/j.bbrep.2021.101021. PMID: 34041373; PMCID: PMC8144350. 2. Gao Z, Milnes JT, Choisy SC, Leach MJ, Hancox JC, James AF. The neuroprotective agent sipatrigine blocks multiple cardiac ion channels and causes triangulation of the ventricular action potential. Clin Exp Pharmacol Physiol. 2005 Dec;32(12):1088-96. doi: 10.1111/j.1440-1681.2005.04312.x. PMID: 16445575. 3. Tsuchida E, Harms JF, Woodward JJ, Bullock R. A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat. J Neurosurg. 1996 Jul;85(1):104-11. doi: 10.3171/jns.1996.85.1.0104. PMID: 8683258.
In vitro protocol:
1. Walsh Y, Leach M, Veale EL, Mathie A. Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092. Biochem Biophys Rep. 2021 May 19;26:101021. doi: 10.1016/j.bbrep.2021.101021. PMID: 34041373; PMCID: PMC8144350. 2. Gao Z, Milnes JT, Choisy SC, Leach MJ, Hancox JC, James AF. The neuroprotective agent sipatrigine blocks multiple cardiac ion channels and causes triangulation of the ventricular action potential. Clin Exp Pharmacol Physiol. 2005 Dec;32(12):1088-96. doi: 10.1111/j.1440-1681.2005.04312.x. PMID: 16445575.
In vivo protocol:
1. Tsuchida E, Harms JF, Woodward JJ, Bullock R. A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat. J Neurosurg. 1996 Jul;85(1):104-11. doi: 10.3171/jns.1996.85.1.0104. PMID: 8683258.
1: Gao Z, Milnes JT, Choisy SC, Leach MJ, Hancox JC, James AF. The neuroprotective agent sipatrigine blocks multiple cardiac ion channels and causes triangulation of the ventricular action potential. Clin Exp Pharmacol Physiol. 2005 Dec;32(12):1088-96. PubMed PMID: 16445575. 2: Tsai SJ. Sipatrigine could have therapeutic potential for major depression and bipolar depression through antagonism of the two-pore-domain K+ channel TREK-1. Med Hypotheses. 2008;70(3):548-50. PubMed PMID: 17703894. 3: McCracken E, Dewar D, McCulloch J. Sipatrigine and oligodendrocyte and axonal pathology following transient focal cerebral ischaemia in the rat. Neuroreport. 2003 Mar 3;14(3):517-20. PubMed PMID: 12634515. 4: Callaway JK, Castillo-Melendez M, Giardina SF, Krstew EK, Beart PM, Jarrott B. Sodium channel blocking activity of AM-36 and sipatrigine (BW619C89): in vitro and in vivo evidence. Neuropharmacology. 2004 Jul;47(1):146-55. PubMed PMID: 15165842. 5: Hainsworth AH, Spadoni F, Lavaroni F, Bernardi G, Stefani A. Effects of extracellular pH on the interaction of sipatrigine and lamotrigine with high-voltage-activated (HVA) calcium channels in dissociated neurones of rat cortex. Neuropharmacology. 2001 May;40(6):784-91. PubMed PMID: 11369032. 6: Muir KW, Holzapfel L, Lees KR. Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke. Cerebrovasc Dis. 2000 Nov-Dec;10(6):431-6. PubMed PMID: 11070372. 7: Calabresi P, Stefani A, Marfia GA, Hainsworth AH, Centonze D, Saulle E, Spadoni F, Leach MJ, Giacomini P, Bernardi G. Electrophysiology of sipatrigine: a lamotrigine derivative exhibiting neuroprotective effects. Exp Neurol. 2000 Mar;162(1):171-9. PubMed PMID: 10716897. 8: Hainsworth AH, McNaughton NC, Pereverzev A, Schneider T, Randall AD. Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca2+ channel currents. Eur J Pharmacol. 2003 Apr 25;467(1-3):77-80. PubMed PMID: 12706458. 9: Meadows HJ, Chapman CG, Duckworth DM, Kelsell RE, Murdock PR, Nasir S, Rennie G, Randall AD. The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K(+) channels TREK-1 and TRAAK. Brain Res. 2001 Feb 16;892(1):94-101. PubMed PMID: 11172753. 10: McNaughton NC, Hainsworth AH, Green PJ, Randall AD. Inhibition of recombinant low-voltage-activated Ca(2+) channels by the neuroprotective agent BW619C89 (Sipatrigine). Neuropharmacology. 2000 Apr 27;39(7):1247-53. PubMed PMID: 10760366. 11: Gersdorff Korsgaard MP, Christophersen P, Ahring PK, Olesen SP. Identification of a novel voltage-gated Na+ channel rNa(v)1.5a in the rat hippocampal progenitor stem cell line HiB5. Pflugers Arch. 2001 Oct;443(1):18-30. PubMed PMID: 11692262. 12: Clutterbuck LA, Posada CG, Visintin C, Riddall DR, Lancaster B, Gane PJ, Garthwaite J, Selwood DL. Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707. doi: 10.1021/jm801180p. PubMed PMID: 19341281. 13: Spadoni F, Hainsworth AH, Mercuri NB, Caputi L, Martella G, Lavaroni F, Bernardi G, Stefani A. Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons. Neuroreport. 2002 Jul 2;13(9):1167-70. PubMed PMID: 12151762. 14: Nelson RM, Lambert DG, Richard Green A, Hainsworth AH. Pharmacology of ischemia-induced glutamate efflux from rat cerebral cortex in vitro. Brain Res. 2003 Feb 21;964(1):1-8. PubMed PMID: 12573507. 15: Liu G, Yarov-Yarovoy V, Nobbs M, Clare JJ, Scheuer T, Catterall WA. Differential interactions of lamotrigine and related drugs with transmembrane segment IVS6 of voltage-gated sodium channels. Neuropharmacology. 2003 Mar;44(3):413-22. PubMed PMID: 12604088. 16: Calabresi P, Picconi B, Saulle E, Centonze D, Hainsworth AH, Bernardi G. Is pharmacological neuroprotection dependent on reduced glutamate release? Stroke. 2000 Mar;31(3):766-72; discussion 773. PubMed PMID: 10700517. 17: Yarov-Yarovoy V, Brown J, Sharp EM, Clare JJ, Scheuer T, Catterall WA. Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na(+) channel alpha subunit. J Biol Chem. 2001 Jan 5;276(1):20-7. PubMed PMID: 11024055. 18: Garthwaite G, Goodwin DA, Garthwaite J. Nitric oxide stimulates cGMP formation in rat optic nerve axons, providing a specific marker of axon viability. Eur J Neurosci. 1999 Dec;11(12):4367-72. PubMed PMID: 10594663. 19: Yarov-Yarovoy V, McPhee JC, Idsvoog D, Pate C, Scheuer T, Catterall WA. Role of amino acid residues in transmembrane segments IS6 and IIS6 of the Na+ channel alpha subunit in voltage-dependent gating and drug block. J Biol Chem. 2002 Sep 20;277(38):35393-401. PubMed PMID: 12130650. 20: Garthwaite G, Brown G, Batchelor AM, Goodwin DA, Garthwaite J. Mechanisms of ischaemic damage to central white matter axons: a quantitative histological analysis using rat optic nerve. Neuroscience. 1999;94(4):1219-30. PubMed PMID: 10625062.