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Purity: ≥98%
CP-640186 HCl is a novel and potent inhibitor of mammalian ACCs (isozyme-nonselective acetyl-CoA carboxylase) with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively; It hash improved metabolic stability in comparison to CP-610431, an analog of CP-640186. Inhibition of ACC, with its resultant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favorably affect the multitude of cardiovascular risk factors associated with the metabolic syndrome. CP-640186 can reduce body weight and improve insulin sensitivity in test animals. CP-640186, also inhibited both isozymes with IC50s of ~55 nM but was 2–3 times more potent than CP-610431 in inhibiting HepG2 cell fatty acid and TG synthesis. CP-640186 also stimulated fatty acid oxidation in C2C12 cells (ACC2) and in rat epitrochlearis muscle strips with EC50s of 57 nM and 1.3 uM.
| ln Vitro |
Treatment with CP-640186 (20 µM; 48 h) can stop H460 cell growth[3]. In C2C12 cells and muscle strips, CP-640186 (0.1 nM-100 µM; 2 h) treatment boosts fatty acid metabolism in a concentration-dependent manner [1]. In HepG2 cells, CP-640186 (0.62-1.8 µM; 2 h) treatment suppresses the synthesis of TG and fatty acids[1].
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| ln Vivo |
The acute effectiveness of CP-640186 (oral gavage; 4.6–21 mg/kg; once) has been demonstrated[1]. When administered at equal doses, CP-640186 (intravenous injection and oral gavage; intravenous dose: 5 mg/kg; oral dose: 10 mg/kg; once) causes less drug exposure in rats than in ob/ob mice[1]. At high exposure levels, CP-640186 (oral gavage; 100 mg/kg; once) treatment completely switches the body's energy source from using carbohydrates to using fatty acids[1].
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| Cell Assay |
Cell Proliferation Assay[3]
Cell Types: Human fibroblasts and H460 cells Tested Concentrations: 20 µM Incubation Duration: 48 hrs (hours) Experimental Results: Led to a ∼30% decrease in cell number compared to vehicle-treated controls. Cell Viability Assay[1] Cell Types: C2C12 cells and muscle strips Tested Concentrations: 0.1 nM-100 µM Incubation Duration: 2 hrs (hours) Experimental Results: Stimulated palmitate acid oxidation with an EC50 of 57 nM and a maximal stimulation of 280% in C2C12 cells. Stimulated palmitate acid oxidation with an EC50 of 1.3 μM and a maximal stimulation of 240% in isolated rat epitrochlearis muscle. Cell Viability Assay[1] Cell Types: HepG2 cells Tested Concentrations: 0.62-1.8 µM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibited fatty acid synthesis and TG synthesis in HepG2 cells with EC50s of 0.62 μM and 1.8 μM, respectfully. |
| Animal Protocol |
Animal/Disease Models: Male ob/ob mice[1]
Doses: 4.6-21 mg/kg Route of Administration: po (oral gavage); 4.6-21 mg/kg; once Experimental Results: Demonstrated acute efficacy for up to 8 h after oral administration, exhibiting ED50 values of 4.6, 9.7, and 21 mg/kg, at 1, 4, and 8 h, respectively, after treatment. Animal/Disease Models: Male SD (Sprague-Dawley) rats[1] Doses: intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg Route of Administration: intravenous (iv) injection and po (oral gavage); intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg; once Experimental Results: demonstrated a plasma half-life of 1.5 h, a bioavailability of 39%, a Clp of 65 ml/min/kg, a Vdss of 5 liters/kg, an oral Tmax of 1.0 h, an oral Cmax of 345 ng/mL, and an oral AUC0-∞ of 960 ng·h /mL. Animal/Disease Models: Male ob/ob mice[1] Doses: intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg Route of Administration: intravenous (iv) injection and po (oral gavage); intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg; once Experimental Results: demonstrated a plasma half-life of 1.1 h, a bioavailability of 50%, a Clp of 54 ml/min/kg, an oral Tmax of 0.25 h, an |
| References |
[1]. Harwood HJ Jr, et al. Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experiment
[2]. Yamashita T, et al. Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6314-8. [3]. Daniel Hess, et al. Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells. PLoS One. 2010 Jun 30;5(6):e11394. |
| Molecular Formula |
C30H36CLN3O3
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| Molecular Weight |
522.08
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| CAS # |
591778-70-0
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| Related CAS # |
CP-640186;591778-68-6
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| SMILES |
O=C(C1=C2C=CC=CC2=CC3=CC=CC=C13)N4CCC(N5C[ C@H](C(N6CCOCC6)=O)CCC5)CC4.[H]Cl
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (191.54 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9154 mL | 9.5771 mL | 19.1542 mL | |
| 5 mM | 0.3831 mL | 1.9154 mL | 3.8308 mL | |
| 10 mM | 0.1915 mL | 0.9577 mL | 1.9154 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Stimulation of rat fatty acid oxidation (respiratory quotient lowering) by CP-640186.J Biol Chem. 2003 Sep 26;278(39):37099-111. |
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Stimulation of fatty acid oxidation in cultured skeletal muscle C2C12 cells and in epitrochlaris muscle slices by CP-640186.J Biol Chem. 2003 Sep 26;278(39):37099-111. |
 Kinetics of ACC1 inhibition by CP-610431.J Biol Chem. 2003 Sep 26;278(39):37099-111. |
 Inhibition of ACC1 and ACC2 activity by CP-610431.J Biol Chem. 2003 Sep 26;278(39):37099-111. |
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 Inhibition of HepG2 cell fatty acid synthesis, TG synthesis, TG secretion, and apoB secretion by CP-610431.J Biol Chem. 2003 Sep 26;278(39):37099-111. |
 Tissue malonyl-CoA lowering by CP-640186.J Biol Chem. 2003 Sep 26;278(39):37099-111. |
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