Description
A-
769662 is a small molecule thienopyridone that activates AMPK directly in cell-
free assays (EC
50 = 116 nM) and intact cells by allosterically activating AMPK and inhibiting its dephosphorylation on Thr
172. 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.
Uses
A 769662 is an AMP-activated protein kinase (AMPK) activiator. A 769662 selectively activates cardiac AMPK heterotrimeric complexes contg. α2/β1-subunits.
Definition
ChEBI: 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-6-oxo-7H-thieno[2,3-b]pyridine-5-carbonitrile is a member of biphenyls.
Biological Activity
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 .
References
1) Scott et al. (2008), Thienopyridone drugs are selective activators of AMP-activated protein kinase beta1-containing complexes; Cell Biol., 15 1220
2) Cool et al. (2006), Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome; Cell Metab., 3 403
3) Zhou et al. (2009), Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase on 3T3-L1 adipogenesis; Biol. Pharm. Bull., 32?993
4) Vazquez-Martin et al. (2012) Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells; Cell Cycle, 11 974
5) Ducommun et al. (2014) Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662; Am. J. Physiol. Endocrinol. Metab., 306 E688
