Art. -Nr.: HY-105191C

Azalanstat mesylate

Name: Azalanstat mesylate
Brand: MedChemExpress
SKU: HY-105191C
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(Synonyms: RS-21607 mesylate)

Azalanstat (RS-21607) mesylate is an orally active lanosterol 14α-demethylase inhibitor. Azalanstat mesylate 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 mesylate is used in the study of hypercholesterolemia.

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CAS. Nr.: 143484-80-4
Formel: C₂₃H₂₈ClN₃O₅S₂
Molecular Weight:526.07

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Azalanstat mesylate Chemical Structure

CAS. Nr.: 143484-80-4

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Biologische Aktivität
- Beschreibung
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Cellular Effect

Cell Line	Type	Value	Description	References
Fibroblast	IC50	0.2 nM	Inhibition of cholesterol synthesis (measured via [¹⁴C]-acetate incorporation into demethyl-sterol/cholesterol fraction) in human fibroblasts, with 1 hr pre-incubation followed by 2 hr pulse with [¹⁴C] sodium acetate. Inhibition of cholesterol synthesis (measured via [¹⁴C]-acetate incorporation into demethyl-sterol/cholesterol fraction) in human fibroblasts, with 1 hr pre-incubation followed by 2 hr pulse with [¹⁴C] sodium acetate.	7646560
HepG2	IC50	6.5 nM	Inhibition of cholesterol synthesis (measured via [¹⁴C]-acetate incorporation into demethyl-sterol/cholesterol fraction) in HepG2 cells, with 1 hr pre-incubation followed by 2 hr pulse with [¹⁴C] sodium acetate. Inhibition of cholesterol synthesis (measured via [¹⁴C]-acetate incorporation into demethyl-sterol/cholesterol fraction) in HepG2 cells, with 1 hr pre-incubation followed by 2 hr pulse with [¹⁴C] sodium acetate.	7646560

In Vitro

Azalanstat (RS-21607) (0.1 nM-10 μM; 1 h pre-incubation, 2 h pulse) mesylate potently inhibits cholesterol synthesis in human fibroblasts (IC₅₀ = 0.2 nM), HepG2 cells (IC₅₀ = 6.5 nM), and hamster hepatocytes (IC₅₀ = 10 nM) by inhibiting lanosterol 14α-demethylase, which leads to the accumulation of methyl sterols without the accumulation of oxidosqualene^[1].
Azalanstat (0.01-100 μM; 20 h) mesylate 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) mesylate 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) mesylate increases specific ¹²⁵I-LDL uptake by approximately 25% in HepG2 cells^[1].
Azalanstat (0.1-100 μM; 10 min pre-incubation, 15 min total incubation at 37 °C) mesylate moderately inhibits rat spleen HO-1 (IC₅₀ = 5.3 μM) and rat brain HO-2 (IC₅₀ = 24.5 μM), with a 4.6-fold selectivity for HO-1 over HO-2^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[1]

Cell Line:

human fibroblasts, HepG2 cells, hamster hepatocytes
Concentration:

0.1, 1.0, 10, 100, 1000, 10000 nM
Incubation Time:

1 hr pre-incubation, 2 hr pulse
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 (RS-21607) (25-100 mg/kg; oral; once daily; for 14 consecutive days) mesylate reduces serum cholesterol in hamsters fed a normal diet in a dose-dependent manner, with an ED₅₀ of 62 mg/kg^[1].
Azalanstat (50 mg/kg; oral; once daily; for 28 days) mesylate 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) mesylate 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) mesylate 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) mesylate 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) mesylate 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) mesylate 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.

Animal Model:

Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001 containing 0.027% cholesterol)^[1]
Dosage:

25 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg
Administration:

p.o.; daily; 14 days
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.

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]
Dosage:

50 mg/kg
Administration:

p.o.; daily; 28 days
Result:

Reduced plasma cholesterol by 37% within 2 weeks.
Maintained plasma cholesterol levels significantly lower than controls for 2 weeks after treatment termination.

Animal Model:

Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)^[1]
Dosage:

50 mg/kg
Administration:

p.o.; daily; 14 days
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.

Animal Model:

Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)^[1]
Dosage:

25 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg
Administration:

p.o.; daily; 14 days
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.

Animal Model:

Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)^[1]
Dosage:

50 mg/kg; 75 mg/kg
Administration:

p.o.; daily; 7-14 days
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.

Animal Model:

Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)^[1]
Dosage:

30 mg/kg; 30 mg/kg plus cholestyramine 500 mg/kg
Administration:

p.o.; daily; 7 days; p.o.; twice daily; 7 days (cholestyramine)
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.

Animal Model:

Golden Syrian hamsters (male, 90-110 g, fed regular Purina Rodent Chow 5001)^[1]
Dosage:

50 mg/kg
Administration:

p.o.; daily; 7-10 days
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

CAS. Nr. 143484-80-4
Molecular Weight 526.07
Formel C₂₃H₂₈ClN₃O₅S₂
SMILES

CS(=O)(O)=O.ClC(C=C1)=CC=C1CC[C@]2(O[C@@H](CO2)CSC3=CC=C(C=C3)N)CN4C=CN=C4
Synonyms

RS-21607 mesylate
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[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.

[2]. Alfredson et al. Enantioselectivity of Azalanstat and Its Ketal Tosylate Intermediate in Chiral High Performance Liquid Chromatography Separations. Journal of Liquid Chromatography & Related Technologies, 19(10), 1653–1668.

[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.

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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Azalanstat mesylate