AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that functions as a metabolic sensor, regulating lipid and glucose metabolism to maintain cellular energy homeostasis and to protect against metabolic stress. 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.