RPR107393 (10 min) is a potent inhibitor of rat liver microsomal squalene synthase with an IC50 value of 0.6 to 0.9 nM and no activity against HMG-CoA reductase in rat liver microsomes (inhibition rate of 3% at 1 mM)[1]. RPR107393 (6 h) inhibited cholesterol biosynthesis (IC50 = 880 nM) and triglyceride biosynthesis (IC50 = 410 nM) in rat hepatocytes in a concentration-dependent manner[2]. RPR107393 (10 μM, 2–24 h) decreased in a time-dependent manner with respect to the degree of [1–14C]acetic acid incorporation into lipids in rat hepatocytes, with the maximum inhibitory effect on cholesterol and triglyceride biosynthesis occurring at 2 h and 24 h, respectively[2]. RPR107393 (1 μM, 4 hours) inhibited the biosynthesis of cholesterol and triglycerides in rat hepatocytes by 82.4% and 70.0%, respectively. The latter effect could be enhanced by MVL supplementation, suggesting that its mechanism of action may be related to the increase of FPP derivatives [2]. RPR107393 (1-10 μM, 4 hours) enhanced carnitine-dependent mitochondrial β-oxidation (increased by 26.5% at 1 μM and 39.5% at 10 μM) and reduced overall triglyceride biosynthesis through a β-oxidation-independent pathway [2]. RPR107393 (10 μM, 4 hours) inhibited triglyceride biosynthesis by reducing fatty acid and triglyceride synthesis in rat hepatocytes by 67.7% and 68.5%, respectively, by inhibiting fatty acid synthesis (rather than subsequent metabolic stages) [2].

RPR107393 (10, 25 and 30 mg/kg, orally, as a single dose, or twice daily for 2–4 days, or once daily for 7 days) exhibited potent lipid-lowering effects in statistical models [1]. RPR107393 (20 mg/kg, once daily, twice daily or once daily for 7 days) selectively lowered low-density lipoprotein cholesterol while maintaining beneficial high-density lipoprotein levels in a marmoset model [1].

Animal/Disease Models: Sprague-Dawley rats (130-150 g)[1]
Doses: 10 and 25 mg/kg
Route of Administration: p.o., sigle dose
Experimental Results: 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/Disease Models: Sprague-Dawley rats (130-150 g)[1]
Doses: 30 mg/kg
Route of Administration: p.o., b.i.d. for 2-4 days
Experimental Results: 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/Disease Models: Sprague-Dawley rats (130-150 g) given a chow diet or the same diet supplemented with 2 % cholestyramine[1]
Doses: 30 mg/kg
Route of Administration: p.o., q.d. for 7 days
Experimental Results: 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/Disease Models: Male common marmosets (Callithrix jacchus)[1]
Doses: 20 mg/kg
Route of Administration: p.o., b.i.d. for 7 days
Experimental Results: 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 or Pravastatin (which produced ≤31% reduction at 50 mg/kg, b.i.d.).

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Animal/Disease Models: Male common marmosets (Callithrix jacchus)[1]
Doses: 20 mg/kg
Route of Administration: p.o., q.d. for 7 days
Experimental Results: 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.

[1]. https://pubmed.ncbi.nlm.nih.gov/9152381/

[2]. https://pubmed.ncbi.nlm.nih.gov/12518031/

C22H24CL2N2O

403.34

190841-57-7

RPR107393 free base; 197576-78-6

Typically exists as solids at room temperature

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)