RPR107393
RPR107393 is an orally active potent selective squalene synthase (SQS) inhibitor. RPR107393 inhibits rat liver microsomal squalene synthase with an IC50 value of 0.8 nM. RPR107393 reduces triglyceride biosynthesis by suppressing fatty acid biosynthesis via an increase in intracellular farnesol and its derivatives. RPR107393 reduces plasma cholesterol in rats and marmosets. RPR107393 can be used for metabolic disease research, such as hypercholesterolemia, hypertriglyceridemia and atherosclerosis.
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- No. CAS: 190841-57-7
- Fòrmula: C22H24Cl2N2O
- Peso molecular:403.34
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
IC50 & Target
IC50: 0.8±0.2 nM (rat liver microsomal squalene synthase)[1]
In Vitro
RPR107393 (10 min) is a potent inhibitor of rat liver microsomal squalene synthase, with IC50 values of 0.6 to 0.9 nM, and is inactive (3% inhibition at 1 mM) against HMG-CoA reductase from rat liver microsomes[1].
RPR107393 (6 h) concentration-dependently inhibits cholesterol biosynthesis (IC50 = 880 nM) and triglyceride biosynthesis (IC50 = 410 nM) in rat hepatocytes[2].
RPR107393 (10 μM, 2-24 h) decreases the incorporation of [1-14C]acetic acid into lipids in rat hepatocytes in a time-dependent manner, with maximal inhibition of cholesterol and triglyceride biosynthesis occurring at 2 h and 24 h, respectively[2].
RPR107393 (1 μM, 4 h) inhibits cholesterol and triglyceride biosynthesis by 82.4% and 70.0% in rat hepatocytes, respectively, with the latter effect potentiated by MVL supplementation, suggesting a mechanism involving increased FPP derivatives[2].
RPR107393 (1-10 μM, 4 h) increases carnitine-dependent mitochondrial β-oxidation (by 26.5% at 1 μM and 39.5% at 10 μM), it reduces overall triglyceride biosynthesis through a β-oxidation-independent pathway[2].
RPR107393 (10 μM, 4 h) suppresses triglyceride biosynthesis in rat hepatocytes, reducing fatty acid and triglyceride synthesis by 67.7% and 68.5%, respectively, through inhibiting fatty acid synthesis rather than later metabolic stages[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
RPR107393 (20 mg/kg, p.o., b.i.d. or q.d. for 7 days) selectively lowers LDL cholesterol while maintaining a favorable HDL profile in marmosets[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley rats (130-150 g)[1]
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Dosage:10 and 25 mg/kg
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Administration:p.o., sigle dose
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Result:Reduced cholesterol biosynthesis by 92% at 10 mg/kg, with an approximate ED50 value of 5 mg/kg.
Reduced cholesterol biosynthesis by 74 % after 6 h, and the time for 50% inhibition was ~7 hr at 10 mg/kg.
Inhibited hepatic cholesterol biosynthesis with an inhibition of 82% at 25 mg/kg after 10 h, but the effect was no longer apparent at 21 h.
Inhibited cholesterol biosynthesis associated with an accumulation of radiolabeled diacid products in the liver.
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Animal Model:Sprague-Dawley rats (130-150 g)[1]
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Dosage:30 mg/kg
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Administration:p.o., b.i.d. for 2-4 days
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Result:Lowered serum cholesterol by 35% after 2 days and by nearly 50% after 3 days.
The reduction in cholesterol was greater in the very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) fractions (66-88%) than in the high-density lipoprotein (HDL) fraction (maximum, 35%).
Reduced serum triglycerides by up to 70%.
Induced hepatic microsomal HMG-CoA reductase activity by 12 to 34-fold.
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Animal Model:Sprague-Dawley rats (130-150 g) given a chow diet or the same diet supplemented with 2 % cholestyramine (HY-104081)[1]
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Dosage:30 mg/kg
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Administration:p.o., q.d. for 7 days
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Result:The R and S enantiomers reduced serum cholesterol by 9% and 24%, and triglycerides by 46% and 57%, respectively.
Coadministration with 2% cholestyramine in the diet reduced serum cholesterol by 49%.
The R enantiomer administered alone did not lower serum LDL cholesterol, whereas coadministration with cholestyramine resulted in a 30% reduction.
The reductions in LDL cholesterol with the S enantiomer in the absence and the presence of cholestyramine were 33% and 61%, respectively.
The reduction was greater in the VLDL and LDL fractions than in the HDL fraction.
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Animal Model:Male common marmosets (Callithrix jacchus)[1]
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Dosage:20 mg/kg
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Administration:p.o., b.i.d. for 7 days
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Result:Reduced plasma cholesterol by 50%.
The reduction in plasma cholesterol was selectively in the LDL fraction (≤50%), whereas cholesterol in the HDL fraction was unchanged.
Produced a greater reduction in plasma cholesterol than Lovastatin (HY-N0504) or Pravastatin (HY-B0165) (which produced ≤31% reduction at 50 mg/kg, b.i.d.).
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Animal Model:Male common marmosets (Callithrix jacchus)[1]
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Dosage:20 mg/kg
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Administration:p.o., q.d. for 7 days
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Result:Both enantiomers reduced total plasma cholesterol by approximately 27%.
The R and S enantiomers reduced LDL cholesterol by 50% and 43%, respectively.
Showed no significant changed in HDL cholesterol levels.
Chemical Information
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No. CAS 190841-57-7
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Peso molecular 403.34
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Fòrmula C22H24Cl2N2O
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SMILES
OC1(C2=CC=C(C3=CC=C4N=CC=CC4=C3)C=C2)CN5CCC1CC5.Cl.Cl
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Cardiovascular Diseases
Cardiovascular disease can be modeled as maladaptive cardiac remodeling, where ischemic injury or pressure overload activates inflammatory signaling, fibroblast activation, extracellular-matrix deposition, cardiomyocyte hypertrophy, vascular remodeling, and progressive ventricular dysfunction. The TGF-β/SMAD axis is a central profibrotic pathway after myocardial injury and pressure overload, while innate immune and cytokine pathways regulate leukocyte recruitment, scar formation, and adverse remodeling. Key unresolved questions include which inflammatory signals are reparative versus harmful, when fibrosis is protective versus maladaptive, and whether pathway inhibition improves function without weakening necessary infarct healing or compensatory remodeling.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Pureza y Documentación
Referencias
[1]. Amin D, et al. RPR107393, a potent squalene synthase inhibitor and orally effective Cholesterol-lowering agent: comparison with inhibitors of HMG-CoA reductase. J Pharmacol Exp Ther. 1997 May;281(2):746-52. [Content Brief]
[2]. Hiyoshi H, et al. Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes. J Lipid Res. 2003 Jan;44(1):128-35. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RPR107393 Related Classifications
HY-100299A Related Classifications
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