CP 640186

SKU: orb1224549

Description

CP-640186 is an isozyme-nonselective Acetyl-CoA carboxylase (ACCase) inhibitor with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively; with improved metabolic stability vs CP-610431.(In Vitro):CP-640186 (20 μM; 48 h) treatment can inhibit H460 cell growth.CP-640186 (0.1 nM-100 μM; 2 h) treatment increases fatty acid metabolism in a concentration-dependent manner in C2C12 cells and muscle strips.CP-640186 (0.62-1.8 μM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells.(In Vivo):CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy.CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses.CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level.

Key Properties

• CAS Number: 591778-68-6
• MW: 485.62
• Purity: >98% (HPLC)
• Formula: C₃₀H₃₅N₃O₃
• SMILES: C1C[C@H](CN(C1)C2CCN(CC2)C(=O)C3=C4C=CC=CC4=CC5=CC=CC=C53)C(=O)N6CCOCC6
• Target: ACC
• Solubility: DMSO: 10 mM

Bioactivity

• In Vivo:
  CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy. CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses. CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level. Animal model: Male ob/ob mice. Dosage: 4.6-21 mg/kg. Administration: Oral gavage; 4.6-21 mg/kg; once. Result: 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 model: Male Sprague-Dawley rats. Dosage: Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg. Administration: Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once. Result: Showed 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 model: Male ob/ob mice. Dosage: Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg. Administration: Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once. Result: Showed 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 oral Cmax of 2177 ng/mL, and an oral AUC0-∞ of 3068 ng h/mL. Animal model: Twenty male Sprague-Dawley rats (350-400 g) fasted and then refed a high sucrose diet for 2 days; additional eight rats fasted for 24 h. Dosage: 100 mg/kg. Administration: Oral gavage; 100 mg/kg; once. Result: Resulted in time-dependent reductions in RQ (a ratio of CO2 production to O2 consumption) of up to 64%.
• In Vitro:
  CP-640186 (20 μM; 48 h) treatment can inhibit H460 cell growth. CP-640186 (0.1 nM-100 μM; 2 h) treatment increases fatty acid metabolism in a concentration-dependent manner in C2C12 cells and muscle strips. CP-640186 (0.62-1.8 μM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells. Cell Proliferation Assay Cell line: Human fibroblasts and H460 cells. Concentration: 20 μM. Incubation time: 48 hours. Result: Led to a ~30% decrease in cell number compared to vehicle-treated controls. Cell Viability Assay Cell line: C2C12 cells and muscle strips. Concentration: 0.1 nM-100 μM Incubation time: 2 hours. Result: 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 Cell line: HepG2 cells. Concentration: 0.62-1.8 μM Incubation time: 6 hours. Result: Inhibited fatty acid synthesis and TG synthesis in HepG2 cells with EC50s of 0.62 μM and 1.8 μM, respecticely.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

ACC