A-769662

A-769662 is a AMP-activated protein kinase (AMPK) activator. A-769662 inhibits the function of the 26S proteasome by an AMPK-independent mechanism and leads to cell cycle arrest. A-769662 directly stimulates partially purified rat liver AMPK (EC₅₀ = 0.8 μM) and inhibits fatty acid synthesis in primary rat hepatocytes (IC₅₀ = 3.2 μM). A-769662 can alleviate the symptoms of metabolic diseases such as type 2 diabetes^[1][2][3][4]. IC50 & Target:EC50: 0.8 μM (AMPK) In Vitro:A-769662 (0.1-100 μM) increases AMPK activity in the presence of a saturating concentration of AMP (300 μM)^[1].
A-769662 (1 nM-1 mM, 4h) increases acetyl-CoA carboxylase (ACC) phosphorylation dose-dependently in primary rat hepatocytes^[1].
A-769662 (50-300 μM, 1 h) increases the GFP-dependent fluorescence dose-dependently in HEK-GFPu-1 cells^[3].
A-769662 (0-50 μM, 1 h) is able to reduce the activity of pre-existing proteasomal activity in MEF cells^[3]. In Vivo:A-769662 (30 mg/kg, i.p., single dose) significantly reduces the respiratory exchange ratio relative to vehicle, indicating increased fatty acid utilization despite the availability of carbohydrates in Sprague Dawley rats^[1].
A-769662 (3-30 mg/kg, i.p., b.i.d., for 5 d) reduces plasma glucose levels, lipids, and ACC activity in ob/ob and lean littermate mice^[1].
A-769662 (3-30 mg/kg, i.p., b.i.d., for 14 d) reduces plasma glucose in ob/ob and lean littermate mice^[1].
A-769662 (10-300 μM, 1 h) inhibits the proteasomal function in mouse embryonic fibroblast (MEF) cells with an IC₅₀ of 62 μM in wild-type and double α1 -/- α1 -/- KO mice ^[3].
A-769662 (300 μM) has toxic effects on MEF cells in wild-type and double α1 -/- α1 -/- KO mice^[3].
A-769662 (15-30 mg/kg, i.p., 2 w) induces AMPK activation that normalizes the nerve functional changes and reduces pain associated with diabetic neuropathy (DN) in diabetic mice^[4].