Biochem/physiol Actions

Primary Targetpyruvate dehydrogenase kinases

Cell permeable: yes

Target IC₅₀: 36.8 & 6.4 nM for PDhK1 & PDhK2, respectively

General description

A cell-permeable, bioavailable trifluomethylpropanamide compound that acts as a potent, selective, reversible, non-ATP-competitive inhibitor of pyruvate dehydrogenase kinases (IC₅₀ = 36.8 & 6.4 nM for PDhK1 & PDhK2, respectively). Inhibits PDhK3 at much higher concentrations (IC₅₀ = 600 nM) and robustly stimulates PDhK4 activity (>10 nM). Also shown to increase pyruvate dehydrogenase (PDh) activity in liver and muscle, and potentiates pyruvate oxidation (EC₅₀ = 105 nM in rat hepatocytes). Occupies lipoyl domain-binding site of PDhK2 (K_d = 19.2 nM) and disrupts the association of PDhK2 and inner lipoyl-bearing domain 2 of dihydrolipoyl acetyltransferase. Improves 24-h glucose profile and eliminates postparandial elevation in blood glucose in Zucker (fa/Fa) rats (10 mg/kg, b.i.d, p.o.,7 days). 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.

Pyruvate Dehydrogenase Kinase Inhibitor, AZD7545, CAS 252017-04-2, is a potent, selective, reversible inhibitor of PDHK2 (IC₅₀ = 6.4 nM). Inhibits PDHK1 at higher levels (IC₅₀ = 36.8 nM).

A cell-permeable, bioavailable trifluomethylpropanamide compound that acts as a potent, selective, reversible, non-ATP-competitive inhibitor of pyruvate dehydrogenase kinases (IC₅₀ = 36.8 & 6.4 nM for PDhK1 & PDhK2, respectively). Inhibits PDhK3 at much higher concentrations (IC₅₀ = 600 nM) and robustly stimulates PDhK4 activity (>10 nM). Also shown to increase pyruvate dehydrogenase (PDh) activity in liver and muscle, and potentiates pyruvate oxidation (EC₅₀ = 105 nM in rat hepatocytes). Occupies lipoyl domain-binding site of PDhK2 (K_d = 19.2 nM) and disrupts the association of PDhK2 and inner lipoyl-bearing domain 2 of dihydrolipoyl acetyltransferase. Improves 24-h glucose profile and eliminates postparandial elevation in blood glucose in Zucker (fa/Fa) rats (10 mg/kg, b.i.d, p.o.,7 days).

Legal Information

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

Other Notes

Li, J., et al. 2009. J. Biol. Chem.284, 34458.Tuganova, A., et al. 2007. Biochemistry46, 8592.Morrell, J.A., et al. 2003. Biochem. Soc. Trans.31, 1168.Mayers, R.M., et al. 2003. Biochem. Soc. Trans.31, 1165.

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)