A 769662

A-769662 is a small molecule thienopyridone that activates AMPK directly in cell-free assays (EC₅₀ = 116 nM) and intact cells by allosterically activating AMPK and inhibiting its dephosphorylation on Thr¹⁷². A-769662 specifically activates β1 subunit-containing AMPK heterotrimers, and its effects are independent of kinases upstream of AMPK. A-769662 has been used to stimulate CYP450-mediated fatty acid oxidation, inhibit adipocyte differentiation, explore glucose uptake in skeletal muscle, and promote endothelial cell survival during metabolic stress.

A 769662 is an AMP-activated protein kinase (AMPK) activiator. A 769662 selectively activates cardiac AMPK heterotrimeric complexes contg. α2/β1-subunits.

ChEBI: 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-6-oxo-7H-thieno[2,3-b]pyridine-5-carbonitrile is a member of biphenyls.

Potent, reversible AMP-activated protein kinase (AMPK) activator (EC 50 = 0.8 μ M) that displays selectivity towards β 1 subunit-containing heterotrimers. Inhibits fatty acid synthesis (IC 50 = 3.2 μ M) and decreases plasma glucose and triglyceride levels in vivo .

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A-769662 is a potent activator of AMP-activated protein kinase by allosterically binding to the β and γ subunits and by inhibiting dephosphorylation of AMPK on Thr172. This small molecule selectively targets AMPK heterotrimers containing the β1 subunit. A-769662 has been shown to stimulate purified rat liver AMPK and inhibit fatty acid synthesis in rat hepatocytes. Treatment of adipocytes with A-769662 inhibits cell differentiation, leads to over-activation of AMPK, and inactivation of acetyl-CoA carboxylase, making this an interesting compound when studying obesity.

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