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| 100mg |
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| 250mg |
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| 500mg |
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| 2g |
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Purity: ≥98%
Stiripentol (formerly known as BCX-2600; BCX2600; STP; trade name: Diacomit) is an FDA-approved anticonvulsant drug that inhibits the activity of several cytochromes P450 (P450s). Stiripentol inhibits N-demethylation of CLB to NCLB mediatated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with Ki of 1.59±0.07 and 0.516±0.065 μM and IC50 of 1.58 and 3.29 μM, respectively. In August 2018, FDA approved Stiripentol to treat seizures associated with Dravet syndrome in patients 2 years of age and older taking clobazam.
| ln Vitro |
Stiripentol (STP) is an anticonvulsant drug that can block CYP3A4's (noncompetitively) and CYP2C19's (competitively) N-demethylation of CLB to N-desmethylclobazam (NCLB). The best models to explain the inhibition of CLB demethylation by Stiripentol (STP) are the competitive inhibition model with Ki=0.52 μM for the cDNA-expressing CYP2C19 and the noncompetitive inhibition model with apparent Ki=1.6 μM for the cDNA-expressing CYP3A4. Stiripentol (STP) has a Ki=0.14 μM and competitively inhibits the formation of OH-NCLB from NCLB by cDNA-expressing CYP2C19[1].
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| ln Vivo |
The difference in temperature between BT1 (39.67±1.09°C) and BT2 (41.32±1.05°C) in mice receiving Stiripentol (STP) monotherapy reaches statistical significance (t=3.097, p<0.05). Between Stiripentol (STP) monotherapy and CLB monotherapy, there is a statistically significant difference in BT2 (t=2.615, p<0.05). The difference between BT1 (40.18±0.58°C) and BT2 (43.03±0.49°C) in mice receiving Stiripentol (STP)+CLB combination therapy reaches statistical significance (t=10.44, p<0.01)[2].
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
After oral administration, stiripentol is quickly and readily absorbed with a median Tmax of two to three hours. The systemic exposure increases dose-proportionally. Stiripentol has a low bioavailability due to water insolubility and extensive metabolism. Stiripentol is mainly eliminated via metabolism. Its metabolites are excreted mainly via the kidney. Urinary metabolites of stiripentol accounted collectively for the majority (73%) of an oral acute dose whereas a further 13-24% was recovered in feces as unchanged drug. The average volume of distribution is 1.03 L/kg but does not display a dose-dependent relationship. Following administration, stiripentol enters the brain and accumulates in the cerebellum and medulla. Plasma clearance decreases markedly at high doses; it falls from approximately 40 L/kg/day at the dose of 600 mg/day to about 8 L/kg/day at the dose of 2,400 mg. Clearance is decreased after repeated administration of stiripentol, probably due to inhibition of the cytochrome P450 isoenzymes responsible for its metabolism. Metabolism / Metabolites Stiripentol is extensively metabolized. About 13 different metabolites have been found in urine. The main metabolic processes are demethylenation (oxidative cleavage of the methylenedioxy ring system) and glucuronidation, although precise identification of the enzymes involved has not yet been achieved. Other metabolic pathways include O-methylation of catechol metabolites, hydroxylation of the t-butyl group, and conversion of the allylic alcohol side-chain to the isomeric 3-pentanone structure. _In vitro_ studies suggested that the phase I metabolism of stiripentol is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Biological Half-Life The elimination half life is approximately ranges from 4.5 to 13 hours, in a dose-dependent manner. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
Limited data are available on the safety of stiripentol, based mainly on open-label and small, placebo controlled clinical trials in children with Dravet syndrome. In these studies, addition of stiripentol to chronic clobazam therapy was not associated with an increased frequency of serum aminotransferase elevations, and there were no instances of clinically apparent liver injury. Long term therapy with stiripentol has been linked to low rates of ALT and alkaline phosphatase elevations but with increases in gamma glutamyl transpeptidase (GGT) in up to 38% of cases. Since its general availability, there have been no published case reports of stiripentol hepatotoxicity. Thus, clinically apparent liver injury due to stiripentol must be rare, if it occurs at all. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because no information is available on the use of stiripentol during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Protein binding of stiripentol is 99%. |
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| Additional Infomation |
Pharmacodynamics
Stiripentol is an antiepileptic agent that works to reduce seizure frequency. It demonstrates anticonvulsant properties when administered alone and may potentiate GABAergic inhibition via several proposed mechanisms. It provides a therapeutic advantage in improving the efficacy of other antiepileptic drugs by inhibiting cytochrome P450 enzymes that normally metabolize those drugs. The anticonvulsant activity of stiripentol is age-dependent, with increased efficacy in younger patients. |
| Molecular Formula |
C₁₄H₁₈O₃
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| Molecular Weight |
234.29
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| Exact Mass |
234.125
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| CAS # |
49763-96-4
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| Related CAS # |
Stiripentol-d9;1185239-64-8
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| PubChem CID |
5311454
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
365.4±11.0 °C at 760 mmHg
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| Melting Point |
73-74ºC
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| Flash Point |
174.8±19.3 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.579
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| LogP |
3.39
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
280
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C(/C=C/C1=CC2=C(C=C1)OCO2)O
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| InChi Key |
IBLNKMRFIPWSOY-FNORWQNLSA-N
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| InChi Code |
InChI=1S/C14H18O3/c1-14(2,3)13(15)7-5-10-4-6-11-12(8-10)17-9-16-11/h4-8,13,15H,9H2,1-3H3/b7-5+
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| Chemical Name |
(E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ol
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2682 mL | 21.3411 mL | 42.6821 mL | |
| 5 mM | 0.8536 mL | 4.2682 mL | 8.5364 mL | |
| 10 mM | 0.4268 mL | 2.1341 mL | 4.2682 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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