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.
理化性质和储存条件
| Molecular Weight (MW) | 522.08 |
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| Formula | C30H36ClN3O3 |
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| CAS No. | 591778-70-0 (HCl); |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: ≥ 48 mg/mL |
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| Water: <1 mg/mL |
| Ethanol: N/A |
| SMILES Code | 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 | CP 640186 HCl; CP640,186 HCl; CP640186; CP-640186; CP-640,186; CP 640,186. |
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实验参考方法
| In Vitro | In vitro activity: CP-640186 HCl is a 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. 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. C
Kinase Assay: CP-640186 HCl is a 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.
Cell Assay: P-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 |
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| In Vivo | In rats, CP-640186 lowered hepatic, soleus muscle, quadriceps muscle, and cardiac muscle malonyl-CoA with ED50s of 55, 6, 15, and 8 mg/kg. Consequently, CP-640186 inhibited fatty acid synthesis in rats, CD1 mice, and ob/ob mice with ED50s of 13, 11, and 4 mg/kg, and stimulated rat whole body fatty acid oxidation with an ED50 of ~30 mg/kg |
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| Animal model | Rats and mice |
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| Formulation & Dosage | 6, 15, and 8 mg/kg (Rat); 13, 11, and 4 mg/kg (mice) |
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| References | J Biol Chem. 2003 Sep 26;278(39):37099-111. Epub 2003 Jul 3. |
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