Azalanstat
Based on 1 Customer Validation
Azalanstat (RS-21607) is an orally active lanosterol 14α-demethylase inhibitor. Azalanstat exerts a cholesterol-lowering effect by inhibiting cholesterol synthesis and regulating HMG-CoA Reductase (HMGCR), and shows an additive effect when used in combination with Cholestyramine (HY-104081). Azalanstat is used in the study of hypercholesterolemia.
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- Pureza : 99.52%
- No. CAS: 143393-27-5
- Fòrmula: C22H24ClN3O2S
- Peso molecular:429.96
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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
Descripciòn
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CYP51 |
In Vitro
Azalanstat (0.01-100 μM; 20 h) exerts a biphasic regulatory effect on HMG-CoA reductase activity in HepG2 cells: it inhibits approximately 40% of the enzyme activity at concentrations of 0.01-1 μM, and stimulates enzyme activity up to 600% at concentrations of 30-100 μM[1].
Azalanstat (0.1-5 μM; 18 h) increases HMG-CoA reductase mRNA levels by 300% at 0.1 μM and by 100% at 5 μM in HepG2 cells, and elevates LDL receptor mRNA levels by 70% at both 0.1 μM and 5 μM, suggesting post-transcriptional regulation of HMG-CoA reductase activity[1].
Azalanstat (0.1-10 μM; 24 h pre-incubation, 3 h LDL uptake) increases specific 125I-LDL uptake by approximately 25% in HepG2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human fibroblasts, HepG2 cells, hamster hepatocytes
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Concentration:0.1, 1.0, 10, 100, 1000, 10000 nM
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Incubation Time:1 hr pre-incubation, 2 hr pulse
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Result:Inhibited cholesterol synthesis in human fibroblasts (IC50 = 0.2 nM), HepG2 cells (IC50 = 6.5 nM), and hamster hepatocytes (IC50 = 10 nM) by blocking lanosterol 14α-demethylase.
In Vivo
Azalanstat (50 mg/kg; oral; once daily; for 28 days) reduces plasma cholesterol by 37% in hamsters fed a high-fat/high-cholesterol diet, and its effect is transiently maintained after drug withdrawal[1].
Azalanstat (50 mg/kg; oral; once daily; for 14 consecutive days) inhibits cholesterol synthesis in hamster tissues by up to 98%. It exhibits no selectivity in tissue distribution and also elevates methyl sterol levels, particularly dihydrolanosterol levels in the liver[1].
Azalanstat (25-100 mg/kg; oral; daily; 14 days) inhibits hepatic microsomal HMG-CoA reductase activity in a dose-dependent manner in hamsters, with an ED50 of 31 mg/kg, and this activity is highly correlated with serum cholesterol reduction[1].
Azalanstat (50-75 mg/kg; oral; daily; for 1-2 weeks) increases hepatic cholesterol 7α-hydroxylase activity in hamsters by 1.5- to 5-fold, and this effect emerges after 1-2 weeks of oral administration at a dose of 50-75 mg/kg[1].
Azalanstat (30 mg/kg; p.o.; once daily; for 7 consecutive days) reduces serum cholesterol in hamsters by 44% and inhibits hepatic HMG-CoA reductase activity; its cholesterol-lowering effect exerts a synergistic effect with Cholestyramine (HY-104081), and it also attenuates Cholestyramine-induced activation of HMG-CoA reductase[1].
Azalanstat (50 mg/kg; oral; daily; 7-10 days) reduces liver-specific LDL binding capacity and LDL receptor protein expression levels in hamsters, while lowering serum cholesterol by up to 53%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001 containing 0.027% cholesterol)[1]
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Dosage:25 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Lowered serum cholesterol in a dose-dependent manner with an ED50 of 62 mg/kg.
Reduced total cholesterol to 91.2 mg/dL, LDL cholesterol to 13.2 mg/dL, apo B to 17.3 mg/dL, and increased the HDL/total cholesterol ratio to 63.4%, while increasing the apo A-1/apo B ratio to 6.5 at 25 mg/kg.
Reduced total cholesterol to 71.8 mg/dL, LDL cholesterol to 9.9 mg/dL, apo B to 15.4 mg/dL, triglycerides to 185.8 mg/dL, increased the HDL/total cholesterol ratio to 66.3%, and increased the apo A-1/apo B ratio to 6.8 at 50 mg/kg.
Reduced total cholesterol to 66.5 mg/dL, LDL cholesterol to 3.5 mg/dL, apo B to 9.1 mg/dL, increased the HDL/total cholesterol ratio to 71.4%, and increased the apo A-1/apo B ratio to 10.0 at 75 mg/kg.
Reduced total cholesterol to 60.7 mg/dL, LDL cholesterol to 6.1 mg/dL, apo B to 11.7 mg/dL, triglycerides to 177.4 mg/dL, increased the HDL/total cholesterol ratio to 68.2%, and increased the apo A-1/apo B ratio to 8.2 at 100 mg/kg.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed high fat diet containing 0.1% cholesterol, 5.9% butter fat, and 6% peanut oil for 4 weeks)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Reduced plasma cholesterol by 37% within 2 weeks.
Maintained plasma cholesterol levels significantly lower than controls for 2 weeks after treatment termination.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Inhibited cholesterol (demethyl-sterol) synthesis by 98% in liver, 95% in kidney, 87% in spleen, 38% in adrenals, 93% in testes, and 95% in small intestine.
Increased methyl-sterol synthesis in all tested tissues.
Elevated hepatic dihydrolanosterol levels ~100-fold.
Raised serum dihydrolanosterol to 0.78 mg/dL.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)[1]
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Dosage:25 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Suppressed hepatic microsomal HMG-CoA reductase activity in a dose-dependent manner with an ED50 of 31 mg/kg.
Showed a strong correlation between serum cholesterol levels and hepatic HMG-CoA reductase activity.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)[1]
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Dosage:50 mg/kg; 75 mg/kg
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Administration:p.o.; daily; 7-14 days
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Result:Induced hepatic cholesterol 7α-hydroxylase activity by 149% at 50 mg/kg for 1 week.
Induced hepatic cholesterol 7α-hydroxylase activity by 235% at 50 mg/kg for 2 weeks.
Induced hepatic cholesterol 7α-hydroxylase activity by 501% at 75 mg/kg for 2 weeks.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)[1]
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Dosage:30 mg/kg; 30 mg/kg plus cholestyramine 500 mg/kg
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Administration:p.o.; daily; 7 days; p.o.; twice daily; 7 days (cholestyramine)
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Result:Reduced serum cholesterol by 44% and suppressed hepatic HMG-CoA reductase activity to 44% of control levels when administered alone.
Reduced serum cholesterol by 58% and attenuated cholestyramine-induced increase in HMG-CoA reductase activity to 171% of control levels when coadministered with cholestyramine.
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Animal Model:Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 7-10 days
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Result:Reduced specific 125I-LDL binding to hepatic membranes to 38% of control levels and reduced serum cholesterol by 41% after 7 days.
Reduced LDL receptor protein expression to 51% of control levels and reduced serum cholesterol by 53% after 10 days.
Chemical Information
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No. CAS 143393-27-5
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Appearance Solid
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Peso molecular 429.96
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Fòrmula C22H24ClN3O2S
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Color White to off-white
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SMILES
ClC(C=C1)=CC=C1CC[C@]2(O[C@@H](CO2)CSC3=CC=C(C=C3)N)CN4C=CN=C4
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Synonyms
RS-21607
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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
In Vitro:
DMSO : 100 mg/mL (232.58 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)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (295 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Burton PM, et al. Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity. Biochemical pharmacology. 1995 Aug 08;50(4):529-44. [Content Brief]
[3]. Roman G, et al. Heme oxygenase inhibition by 2-oxy-substituted 1-(1H-imidazol-1-yl)-4-phenylbutanes: effect of halogen substitution in the phenyl ring. Bioorg Med Chem. 2007 May 1;15(9):3225-34. [Content Brief]
[4]. Vlahakis JZ, et al. Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors. Bioorganic & medicinal chemistry letters. 2005 Mar 01;15(5):1457-61. [Content Brief]
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 | 2.3258 mL | 11.6290 mL | 23.2580 mL | 58.1449 mL |
| 5 mM | 0.4652 mL | 2.3258 mL | 4.6516 mL | 11.6290 mL | |
| 10 mM | 0.2326 mL | 1.1629 mL | 2.3258 mL | 5.8145 mL | |
| 15 mM | 0.1551 mL | 0.7753 mL | 1.5505 mL | 3.8763 mL | |
| 20 mM | 0.1163 mL | 0.5814 mL | 1.1629 mL | 2.9072 mL | |
| 25 mM | 0.0930 mL | 0.4652 mL | 0.9303 mL | 2.3258 mL | |
| 30 mM | 0.0775 mL | 0.3876 mL | 0.7753 mL | 1.9382 mL | |
| 40 mM | 0.0581 mL | 0.2907 mL | 0.5814 mL | 1.4536 mL | |
| 50 mM | 0.0465 mL | 0.2326 mL | 0.4652 mL | 1.1629 mL | |
| 60 mM | 0.0388 mL | 0.1938 mL | 0.3876 mL | 0.9691 mL | |
| 80 mM | 0.0291 mL | 0.1454 mL | 0.2907 mL | 0.7268 mL | |
| 100 mM | 0.0233 mL | 0.1163 mL | 0.2326 mL | 0.5814 mL |
Azalanstat Related Classifications
HY-105191 Related Classifications
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Keywords
- Azalanstat
- 143393-27-5
- RS-21607
- RS21607
- RS 21607
- HMG-CoA Reductase (HMGCR)
- Cytochrome P450
- CYPs
- mouse blastocyst
- heme oxygenase-2
- heme oxygenase-1
- hamster hepatocytes
- hepatic microsomal cholesterol 7α-hydroxylase
- lanosterol 14α-demethylase
- hypercholesterolemia
- human fibroblasts
- hepatic microsomal HMG-CoA reductase
- HepG2 cells
- Inhibitor
- inhibitor
- inhibit