MI-883
Based on 1 Customer Validation
MI-883 is orally active constitutive androstane receptor (CAR) (EC50 of 73 nM) agonist and pregnane X Receptor (PXR) (IC50 of 100 nM) antagonist. MI-883 binds to CAR and PXR ligand-binding domains, promotes CAR LBD assembly, activates CAR3 variant, stimulates CAR cytoplasmic-nuclear translocation, upregulates CAR target genes, recruits coactivators NCOA1, NCOA2, NCOA3, inhibits basal and agonist-induced PXR activation, downregulates PXR target genes, disrupts PXR-NCOR2 interaction, blocks agonist-mediated PXR-NCOA1 recruitment. MI-883 reduces plasma total cholesterol, LDL cholesterol, and hepatic free cholesterol levels, increases fecal bile acid excretion, regulates genes involved in xenobiotic metabolism, cholesterol homeostasis, and bile acid homeostasis. MI-883 exhibits metabolic stability, liver-predominant distribution, a safety profile with no observed toxicity, and does not stimulate human hepatocyte hypertrophy or hyperplasia. MI-883 can be used for the research of diet-induced hypercholesterolemia.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.57%
- No. CAS: 2530027-71-3
- Fòrmula: C23H15Cl2FN6O
- Peso molecular:481.31
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
MI-883 (10 pM-30 μM) potently activates recombinant human CAR LBD with an EC50 of 73 nM in a TR-FRET coactivator binding assay[1].
MI-883 (10 pM-30 μM; 24 h) activates human CAR LBD assembly in HepG2 cells with an EC50 of 0.38 μM[1].
MI-883 (10 pM-30 μM; 24 h) activates the human CAR3 variant in HepG2 cells with an EC50 of 0.38 μM[1].
MI-883 (10 pM-30 μM; 24 h) suppresses basal and Rifampicin (HY-B0272)-induced human PXR activation in HepG2 cells with IC50 values of 2.03 μM and 3.60 μM, respectively[1].
MI-883 (5 μM) stimulates translocation of the EGFP-CAR+A fusion protein to the nucleus in COS-1 cells, with ~90% nuclear localization observed[1].
MI-883 (1 μM, 5 μM, 10 μM; 24 h, 48 h) significantly upregulates CYP2B6 mRNA in HepaRG cells and primary human hepatocytes in a CAR-dependent manner, with no effect in CAR-ablated HepaRG KO CAR cells[1].
MI-883 (10 pM-30 μM) competes for binding to recombinant human PXR LBD with an IC50 of 0.10 μM in a TR-FRET competitive binding assay[1].
MI-883 (10 μM, 30 μM; 24 h) stimulates human PXR LBD assembly in HepG2 cells, confirming direct binding to the PXR ligand binding pocket[1].
MI-883 (10 μM, 30 μM; 24 h) acts as a PXR antagonist/inverse agonist in HepG2 cells, blocking rifampicin-induced coactivator recruitment and disrupting PXR-corepressor interactions[1].
MI-883 (1 μM, 5 μM, 10 μM, 20 μM; 24 h, 48 h) significantly downregulates basal and Rifampicin-induced CYP3A4 mRNA in LS174T cells, HepaRG cells, and primary human hepatocytes in a PXR-dependent manner, with no effect in PXR-ablated HepaRG KO PXR cells[1].
MI-883 (100 μM) recruits coactivators NCOA1, NCOA2, and NCOA3 to recombinant human CAR LBD, consistent with CAR agonist activity[1].
MI-883 (1 μM, 5 μM, 10 μM, 20 μM; 48 h) modulates expression of cholesterol and bile acid homeostasis genes in HepaRG cells and primary human hepatocytes, with CAR-dependent downregulation of SREBF1, PXR-dependent upregulation of LDLR, and complex regulation of CYP7A1 dependent on CAR presence[1].
MI-883 (5 μM; 8 h, 12 h, 24 h, 48 h, 72 h, 120 h) upregulates CYP2B6 mRNA and downregulates CYP3A4 mRNA in 3D primary human hepatocyte spheroids over a 120-hour treatment period[1].
MI-883 (5 μM; 72 h) does not reduce ATP production in 3D primary human hepatocyte spheroids after 72 hours of treatment, indicating no cytotoxicity[1].
MI-883 (5 μM; 72 h) does not upregulate proliferative biomarkers in 3D primary human hepatocyte spheroids after 72 hours of treatment, indicating no induction of hepatocyte proliferation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepaRG cells and primary human hepatocytes
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Concentration:1 μM, 5 μM, 10 μM
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Incubation Time:24 h, 48 h
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Result:Significantly upregulated CYP2B6 mRNA.
MI-883 (5 mg/kg; p.o.; every other day; 5 doses total) significantly reduces plasma total, LDL, and HDL cholesterol levels in humanized PXR-CAR-CYP3A4/CYP3A7 mice with high-cholesterol diet-induced hypercholesterolemia[1].
MI-883 (10 mg/kg; i.p.; once every 24 hours; 3 days) significantly induces hepatic Cyp2b10 mRNA expression but does not induce CYP3A4 mRNA expression in chow diet-fed humanized PXR-CAR-CYP3A4/3A7 mice[1].
MI-883 (2.5 mg/kg; p.o.; once daily; 7 days) does not significantly alter plasma cholesterol levels or hepatotoxicity biomarkers but induces hepatic CYP2B6 mRNA expression in PXB-mouse humanized liver mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Humanized PXR-CAR-CYP3A4/3A7 mice (male and female, 10-15 weeks old, diet-induced metabolic syndrome model)[1]
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Dosage:5 mg/kg
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Administration:p.o.; 3x per week; 4 weeks
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Result:Significantly reduced plasma total cholesterol, LDL cholesterol, and HDL cholesterol levels in both male and female mice
Significantly decreased free cholesterol content in male livers; total cholesterol, cholesteryl esters, and lathosterol levels were unchanged.
Significantly increased total fecal bile acid content over 24 hours, with significant increases in β-muricholic acid (βMCA) and chenodeoxycholic acid (CDCA) vs. vehicle.
Significantly upregulated hepatic mRNA expression of xenobiotic metabolism genes (Cyp2b10, Ugt1a1, Ugt2c34, Sult2a1, Abcc4) and bile acid synthesis enzymes (Cyp7a1, Cyp8b1) at the protein level; downregulated hepatic mRNA expression of lipid metabolism genes (Scd1, Fabp2, Srebf1, Scarb1, Angptl3, Lipc) and ileal bile acid transporters (Slc10a2/Asbt, Slc51a).
No significant effects on body weight, food intake, plasma glucose, triglycerides, liver histology, or hepatotoxicity/nephrotoxicity biomarkers.
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Animal Model:Humanized PXR-CAR-CYP3A4/3A7 mice (male and female, 18-26 weeks old, high-cholesterol diet-induced model)[1]
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Dosage:5 mg/kg
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Administration:p.o.; every other day; 5 doses total
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Result:Significantly reduced plasma total cholesterol, LDL cholesterol, and HDL cholesterol levels vs. vehicle.
No significant effects on body weight, liver weight, liver-to-body weight ratio, plasma glucose, or triglycerides (except a minor statistically significant increase in female triglycerides).
Chemical Information
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No. CAS 2530027-71-3
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Appearance Solid
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Peso molecular 481.31
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Fòrmula C23H15Cl2FN6O
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Color White to off-white
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SMILES
O=C(C1=CC(CN2N=NC(C3=C(C4=CC=C(Cl)C=C4)N=C5C=C(C=CN53)F)=C2)=CC=C1Cl)N
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 25 mg/mL (51.94 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (283 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0777 mL | 10.3883 mL | 20.7766 mL | 51.9416 mL |
| 5 mM | 0.4155 mL | 2.0777 mL | 4.1553 mL | 10.3883 mL | |
| 10 mM | 0.2078 mL | 1.0388 mL | 2.0777 mL | 5.1942 mL | |
| 15 mM | 0.1385 mL | 0.6926 mL | 1.3851 mL | 3.4628 mL | |
| 20 mM | 0.1039 mL | 0.5194 mL | 1.0388 mL | 2.5971 mL | |
| 25 mM | 0.0831 mL | 0.4155 mL | 0.8311 mL | 2.0777 mL | |
| 30 mM | 0.0693 mL | 0.3463 mL | 0.6926 mL | 1.7314 mL | |
| 40 mM | 0.0519 mL | 0.2597 mL | 0.5194 mL | 1.2985 mL | |
| 50 mM | 0.0416 mL | 0.2078 mL | 0.4155 mL | 1.0388 mL |
MI-883 Related Classifications
HY-173033 Related Classifications
Powered by Bioz
- MI-883
- 2530027-71-3
- MI883
- MI 883
- Constitutive Androstane Receptor
- Pregnane X Receptor (PXR)
- Cytochrome P450
- primary human hepatocytes
- diet-induced hypercholesterolemia
- humanized PXR-CAR-CYP3A4/3A7 mice
- LS174T cells
- human constitutive androstane receptor
- HepG2 cells
- human pregnane X receptor
- COS-1 cells
- HepaRG cells
- NCOA1
- Inhibitor
- inhibitor
- inhibit