| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
CYP3A4 (cytochrome P450 3A4).
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|---|---|
| ln Vitro |
ML368 is a potent CYP3A4 inhibitor with IC50 values of 9 nM (midazolam → 1'-hydroxymidazolam), 4 nM (testosterone → 6β-hydroxytestosterone), and 38 nM (vincristine → vincristine M1). It displays >2,000-fold selectivity over CYP3A5. SR-9186 inhibits the development of hepatic stage Plasmodium falciparum and blocks ivermectin metabolism. The compound is a valuable tool for studying CYP3A4-mediated drug metabolism and drug-drug interactions.
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| ln Vivo |
In vivo efficacy data for ML368 is limited. The compound is primarily used as an in vitro tool for studying CYP3A4-mediated drug metabolism. SR-9186 inhibits the development of hepatic stage Plasmodium falciparum, suggesting potential antimalarial activity. It also blocks ivermectin metabolism, indicating potential applications in modulating drug exposure. Further in vivo studies would be needed to assess its therapeutic potential.
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| Enzyme Assay |
The in vitro enzyme assay for CYP3A4 inhibition uses recombinant human CYP3A4 enzyme and specific probe substrates (midazolam, testosterone, or vincristine). The enzyme is incubated with the probe substrate, NADPH, and varying concentrations of ML368 (typically 0.01 nM to 100 µM) at 37°C for 10-30 minutes. The reaction is stopped by cooling and addition of acetonitrile. Metabolite formation (1'-hydroxymidazolam, 6β-hydroxytestosterone, or vincristine M1) is quantified by LC-MS/MS. The IC50 is calculated from dose-response curves. Selectivity is assessed by profiling against CYP3A5 and other CYP450 isoforms.
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| Cell Assay |
In vitro cellular assays are performed using human hepatocytes or CYP3A4-expressing cell lines. Cells are treated with ML368 at concentrations ranging from 0.01 to 100 µM for 1-24 hours. CYP3A4 activity is measured by incubating cells with probe substrates (e.g., midazolam) and quantifying metabolite formation by LC-MS/MS. Cytotoxicity is assessed using MTT or LDH release assays. For antimalarial activity, Plasmodium falciparum hepatic stage development is assessed in the presence of ML368.
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| Animal Protocol |
In vivo animal model data for ML368 is not extensively reported in the literature. As a research tool for studying CYP3A4-mediated drug metabolism, the compound would typically be evaluated in pharmacokinetic interaction studies in rodents or non-human primates. Standard studies would involve administration of a CYP3A4 probe substrate (e.g., midazolam) with and without ML368, followed by measurement of substrate and metabolite levels in plasma. Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and tissue distribution would be assessed.
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| ADME/Pharmacokinetics |
ML368 has a molecular weight of 430.5 g/mol and molecular formula C26H18N6O. It is soluble in DMSO (10 mM) and should be stored as a powder at -20°C. Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and tissue distribution are not extensively characterized in publicly available literature. As a research compound, it is typically used in in vitro assays at concentrations ranging from nanomolar to low micromolar.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for ML368. As a research compound, it is not intended for human use and has not undergone formal toxicological evaluation. Standard preclinical safety assessments for CYP450 inhibitors would typically include selectivity profiling against a panel of CYP450 isoforms to assess off-target effects, hERG channel inhibition for cardiac safety, and assessment of potential for mechanism-based inactivation of CYP3A4. The compound is supplied as a solid and should be stored desiccated at -20°C.
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| References | |
| Additional Infomation |
ML368 is a research-grade CYP3A4 inhibitor with >2,000-fold selectivity over CYP3A5. It is not approved for clinical use. The compound is also known as SR9186. It inhibits the development of hepatic stage Plasmodium falciparum and blocks ivermectin metabolism. ML368 is used as a chemical tool to study CYP3A4-mediated drug metabolism and drug-drug interactions. It is supplied as a solid with high purity and should be stored desiccated at -20°C.
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| Molecular Formula |
C28H19F3N6O3
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|---|---|
| Molecular Weight |
544.49
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| Exact Mass |
430.154
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| CAS # |
1361414-26-7
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| PubChem CID |
57391832
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| Appearance |
Yellow to brown solid powder
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| LogP |
5.953
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
697
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FEDMEJWMCJAMHE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H18N6O/c27-15-17-1-3-18(4-2-17)19-5-9-21(10-6-19)31-26(33)32-22-11-7-20(8-12-22)23-13-14-28-25-24(23)29-16-30-25/h1-14,16H,(H,28,29,30)(H2,31,32,33)
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| Chemical Name |
1-[4-(4-cyanophenyl)phenyl]-3-[4-(1H-imidazo[4,5-b]pyridin-7-yl)phenyl]urea
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| Synonyms |
ML 368; ML-368; ML368
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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 |
| 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) |
DMSO : ~31.25 mg/mL (~72.60 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8366 mL | 9.1829 mL | 18.3658 mL | |
| 5 mM | 0.3673 mL | 1.8366 mL | 3.6732 mL | |
| 10 mM | 0.1837 mL | 0.9183 mL | 1.8366 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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