| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
AhR (aryl hydrocarbon receptor). CYP2E1 (transcription inhibition).
|
|---|---|
| ln Vitro |
Mivotilate is a strong, non-toxic aryl hydrocarbon receptor agonist. Histidine 285 mutation to tyrosine is tolerated by the new activation method of movitilate (YH439) [1]. Mivotilate activates the aryl hydrocarbon (Ah) receptor to promote cytochrome P4501A1/2 (CYP1A1/2) [3].
Mivotilate is a non-toxic and potent activator of the aryl hydrocarbon receptor (AhR). It has a novel activation mode that tolerates mutation of histidine 285 to tyrosine. Mivotilate causes induction of cytochromes P4501A1/2 (CYP1A1/2) through the Ah receptor. It functions as a hepatoprotective agent. In vitro studies have characterized its ability to activate AhR and induce CYP1A1/2 expression. |
| ln Vivo |
In rats, CYP2E1-mediated NDMA demethylase activity can be decreased by mivotilate (YH439, 150 mg/kg, oral), although NADPH-dependent P450 oxidoreductase activity is unaffected. Immunoreactive CYP2E1 protein is quickly reduced by migratetilate (75–300 mg/kg). In rats, imivotilate (150 mg/kg, po) suppresses CYP2E1 transcription [2].
Mivotilate (150 mg/kg, p.o.) inhibits the transcription of CYP2E1 in rats. At doses of 75-300 mg/kg, it rapidly decreases immunoreactive CYP2E1 protein. Mivotilate (150 mg/kg, p.o.) reduces CYP2E1-mediated NDMA demethylase activity in rats without significantly affecting NADPH-dependent P450 oxidoreductase activity. These effects suggest a role for Mivotilate in modulating drug metabolism and protecting the liver from CYP2E1-mediated toxicity. |
| Enzyme Assay |
The in vitro enzyme assay for AhR activation uses a cell-based reporter system where AhR activation drives expression of a reporter gene (e.g., luciferase). Cells (e.g., HepG2 or HEK293) are transfected with an AhR-responsive luciferase reporter plasmid and treated with varying concentrations of Mivotilate (typically 0.1 to 100 µM) for 24 hours. Luciferase activity is measured and compared to vehicle control. CYP1A1/2 enzyme activity is measured using the ethoxyresorufin-O-deethylase (EROD) assay, where CYP1A1/2 converts ethoxyresorufin to resorufin, a fluorescent product.
|
| Cell Assay |
In vitro cellular assays are performed using hepatocytes or hepatoma cell lines (e.g., HepG2). Cells are treated with Mivotilate at concentrations ranging from 0.1 to 100 µM for 24-48 hours. CYP1A1 and CYP1A2 mRNA levels are measured by qRT-PCR. CYP1A1/2 enzyme activity is measured using the EROD assay. AhR activation is confirmed by measuring nuclear translocation of AhR using immunofluorescence or by measuring expression of AhR target genes (e.g., CYP1A1, CYP1A2). Cytotoxicity is assessed using MTT or LDH release assays to confirm the non-toxic nature of the compound.
|
| Animal Protocol |
In vivo animal studies are performed using rats. Mivotilate is administered orally at doses of 75-300 mg/kg. Liver tissue is collected at various time points (e.g., 4-24 hours post-dose) for analysis. CYP2E1 protein levels are measured by Western blot or immunohistochemistry. CYP2E1 enzyme activity is measured using NDMA demethylase assays. NADPH-dependent P450 oxidoreductase activity is measured as a control to assess selectivity. Blood samples are collected for pharmacokinetic analysis.
|
| ADME/Pharmacokinetics |
Mivotilate has a molecular weight of 330.45 g/mol and molecular formula C12H14N2O3S3. It is soluble in DMSO (12.5 mg/mL) and corn oil (5 mg/mL). The compound should be stored as a powder at -20°C. Oral bioavailability and detailed pharmacokinetic parameters have been characterized in rats. Mivotilate is administered orally at doses of 75-300 mg/kg in preclinical studies. It is stable under inert atmosphere at 2-8°C for long-term storage.
|
| Toxicity/Toxicokinetics |
Mivotilate is reported to be non-toxic. As a research compound, it has been evaluated in preclinical studies for hepatoprotective activity. Standard toxicology assessments would include acute and repeated-dose toxicity studies in rodents. The compound's non-toxic profile makes it a valuable tool for studying AhR biology and CYP2E1 regulation without the confounding effects of toxicity. It is for research use only and not for human therapeutic use.
|
| References |
|
| Additional Infomation |
Mivotilate is an aromatic amide, isopropyl ester, and secondary carboxylamide.
Mivotilate is a research-grade AhR activator and hepatoprotective agent. It is not approved for clinical use. The compound is also known as YH439. It inhibits CYP2E1 transcription and reduces CYP2E1-mediated enzyme activity in rats. Mivotilate is supplied as a solid with high purity and should be stored desiccated at -20°C. It is a valuable tool for studying AhR signaling, CYP2E1 regulation, and hepatoprotection. |
| Molecular Formula |
C12H14N2O3S3
|
|---|---|
| Molecular Weight |
330.435
|
| Exact Mass |
330.017
|
| CAS # |
130112-42-4
|
| PubChem CID |
148185
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.467g/cm3
|
| Index of Refraction |
1.68
|
| LogP |
3.063
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
20
|
| Complexity |
434
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WOUUWUGULFOVHG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C12H14N2O3S3/c1-6(2)17-10(16)8(11-19-5-20-11)9(15)14-12-13-7(3)4-18-12/h4,6H,5H2,1-3H3,(H,13,14,15)
|
| Chemical Name |
propan-2-yl 2-(1,3-dithietan-2-ylidene)-3-[(4-methyl-1,3-thiazol-2-yl)amino]-3-oxopropanoate
|
| Synonyms |
YH-439; YH 439; Mivotilate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~12.5 mg/mL (~37.83 mM)
|
|---|---|
| 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 | 3.0263 mL | 15.1313 mL | 30.2627 mL | |
| 5 mM | 0.6053 mL | 3.0263 mL | 6.0525 mL | |
| 10 mM | 0.3026 mL | 1.5131 mL | 3.0263 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
