5.33639

Pyruvate Dehydrogenase Kinase Inhibitor, AZD7545

• Sinónimos: Pyruvate Dehydrogenase Kinase Inhibitor, AZD7545, PDK Inhibitor, ( R)-4-(3-Chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenylsulfonyl)-N,N-dimethylbenzamide, PDh Kinase Inhibitor, PDhK Inhibitor
• Fórmula empírica (notación de Hill): C₁₉H₁₈ClF₃N₂O₅S
• Número de CAS: 252017-04-2
• Peso molecular: 478.87
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• Análisis: ≥98% (HPLC)
• Nivel de calidad: 100
• formulario: solid
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: white
• solubilidad: DMSO: 50 mg/mL
• temp. de almacenamiento: 2-8°C
• InChI: 1S/C19H18ClF3N2O5S/c1-18(28,19(21,22)23)17(27)24-15-9-8-13(10-14(15)20)31(29,30)12-6-4-11(5-7-12)16(26)25(2)3/h4-10,28H,1-3H3,(H,24,27)/t18-/m1/s1
• Clave InChI: DTDZLJHKVNTQGZ-GOSISDBHSA-N

Descripción

Descripción general

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).

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).

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
pyruvate dehydrogenase kinases

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

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

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

Otras notas

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.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable