5.33978

ACC Inhibitor IV, CP-640186

• Synonym(s): ACC Inhibitor IV, CP-640186, 9-Anthryl((3 R)-3-(4-morpholinylcarbonyl)-1,4ʹ-bipiperidin-1ʹ-yl)methanone, HCl, Acetyl-CoA Carboxylase Inhibitor IV, CP-640186, HCl
• Empirical Formula (Hill Notation): C₃₀H₃₅N₃O₃
• Molecular Weight: 485.62

Properties

• Assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated (hygroscopic); protect from light
• color: light orange
• solubility: DMSO: 50 mg/mL; H₂O: 50 mg/mL
• storage temp.: 2-8°C

Description

General description

A cell-permeable, orally active, non-toxic bipiperidylcarboxamide derived compound that binds to the active site of acetyl-CoA carboxylase (ACC) at the interface between the two monomers of the CT dimer and acts as a potent, allosteric, and reversible, inhibitor of ACC (IC₅₀ = 53 nM and 61 nM for rat liver ACC1 and ACC2). The inhibition is uncompetitive with respect to ATP and non-competitive with respect to acetyl-CoA, citrate, and bicarbonate. Shown to inhibit fatty acid synthesis in Sprague-Dawley rats, and in CD1 and ob/ob mice (ED₅₀ = 13, 11, and 4 mg/kg). Stimulates fatty acid oxidation in CC12 cells in rat epitrochelearis muscle (ED₅₀ = 57 nM) and reduces muscle malonyl-CoA levels. Improves insulin sensitivity in diet-induced obese animal models. Displays good metabolic stability and moderate pharmacokinetic properties (plasma half-life =1.5 h; C_max = 345 ng/ml; and AUC = 960 ng/h/ml at 5 mg/kg i.v. or 10 mg/kg p.o.).

A cell-permeable, orally active, non-toxic bipiperidylcarboxamide derived compound that binds to the active site of acetyl-CoA carboxylase (ACC) at the interface between the two monomers of the CT dimer and acts as a potent, allosteric, and reversible, inhibitor of ACC (IC₅₀ = 53 nM and 61 nM for rat liver ACC1 and ACC2). The inhibition is uncompetitive with respect to ATP and non-competitive with respect to acetyl-CoA, citrate, and bicarbonate. Shown to inhibit fatty acid synthesis in Sprague-Dawley rats, and in CD1 and ob/ob mice (ED₅₀ = 13, 11, and 4 mg/kg). Stimulates fatty acid oxidation in CC12 cells in rat epitrochelearis muscle (ED₅₀ = 57 nM) and reduces muscle malonyl-CoA levels. Improves insulin sensitivity in diet-induced obese animal models. Displays good metabolic stability and moderate pharmacokinetic properties (plasma half-life =1.5 h; C_max = 345 ng/ml; and AUC = 960 ng/h/ml at 5 mg/kg i.v. or 10 mg/kg p.o.).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

ACC Inhibitor IV, CP-640186, is a cell-permeable, potent, allosteric, eversible inhibitor of ACC (IC₅₀ = 53 and 61 nM for rat liver ACC1 & ACC2). The inhibition is uncompetitive with respect to ATP.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Acetyl-CoA carboxylase (ACC)

Target IC₅₀: 53 nM and 61 nM for rat liver ACC1 and ACC2

Warning

Toxicity: Standard Handling (A)

Physical form

Supplied as a hydrochloride salt.

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Tong, L., and Harwood, H.J., 2006. J. Cell. Biol.99, 1476.
Gu, Y.G., et al. 2006. J. Med. Chem.49, 3770.

Zhang, H., et al. 2004. Structure12, 1683.

Harwood, H.J., et al. 2003. J. Biol. Chem.278, 37099.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3