|A-769662AMPK activator,potent and reversible|
Sample solution is provided at 25 µL, 10mM.
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|Description||A-769662 is a small-molecule activator of AMPK with EC50 value of 116 nM.|
|IC50||116 nM (EC50)|
|Cas No.||844499-71-4||SDF||Download SDF|
|Solubility||Soluble in DMSO > 10 mM||Storage||Store at -20°C|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Shipping Condition||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
A-769662 is a potent activator of AMPK with EC50 value of 0.8 μM in vitro.
AMPK(AMP-activated protein kinase) is a serine/threonine protein kinase which is formed by three proteins: α,β and γ subunits. They play important roles in both the activity and stabilities of AMPK. AMPK functions as sensors of cellular energy by detecting and reacting to the change of AMP: ATP ratio. AMPK plays an important role in regulating intracellular energy metabolism. AMPK inhibits ATP-consuming pathways containing cholesterol synthesis, fatty acid synthesisand gluconeogenesis. AMPK stimulates fatty acid oxidation and glycolysis which are ATP-generating processes. AMPK inhibits gluconeogenesis by suppressing the expression of glucose-6-phosphatase and PEPCK wich are two key gluconeogenic enzymes.
A-769662 belongs to the thienopyridone family. It activates the activity of purified AMPK from diffrent tissues with a dose-dependent manner. A-769662 activated the activity of AMPK extracted from human embryonic kidney cells (HEKs), rat muscle, or rat heart with EC50 values of 1.1 mM, 1.9 mM, or 2.2mM, respectively. A-769662 inhibited the synthesis of fatty acid with IC50 value of 3.2mM in primary rat hepatocytes. A769662 also has inhibition effect on the 26S proteasome with an AMPK-independent mechanism. A769662 does not inhibit the proteolytic activities of the 20S core subunit which is a novel mechanism. A769662 can cause the arrest of cell cycle by inhibiting the 26S proteasome. A-769662 activates AMPK in an allosterically manner. It also inhibits Thr-172 dephosphorylation of AMPK.
In mice treated with dose of 30mg/kg, A-769662 decreased the expression of FAS, G6Pase, and PEPCK in liver of. It also lowered plasma glucose by 40% and reduced body weight gain.
. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R et al: Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 2006, 3(6):403-416.
. Moreno D, Knecht E, Viollet B, Sanz P: A769662, a novel activator of AMP-activated protein kinase, inhibits non-proteolytic components of the 26S proteasome by an AMPK-independent mechanism. FEBS Lett 2008, 582(17):2650-2654.
. Sanders MJ, Ali ZS, Hegarty BD, Heath R, Snowden MA, Carling D: Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem 2007, 282(45):32539-32548.