Inhibiteur ACC IV ; CP - 640186 1 pc x 5 mg

Non disponible en dehors du Royaume-Uni et de l'Irlande

Biochem/physiol Actions

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

Cell permeable: yes

Primary TargetAcetyl-CoA carboxylase (ACC)

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.

Legal Information

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

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.r>Zhang, H., et al. 2004. Structure12, 1683.r>Harwood, H.J., et al. 2003. J. Biol. Chem.278, 37099.

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.

Warning

Toxicity: Standard Handling (A)