Stemcell, 72922, A769662

A769662 is a cell-permeable, direct activator of AMP-activated protein kinase (AMPK) with an EC₅₀ of 116 nM (Goransson et al.). A 4.1-fold stimulation of AMPK is observed, via an allosteric mechanism, which potentially inhibits dephosphorylation on Thr172 (Goransson et al.; Sanders et al.). A769662 specifically activates β1 subunit–containing AMPK heterotrimers, and its effects are independent of kinases upstream of AMPK. Activation of AMPK can inhibit the mTORC1 signaling pathway (Huang et al.). A769662 is also an inhibitor of Na(+)-K(+)-ATPase (Benziane et al.).

REPROGRAMMING

· Inhibits reprogramming of mouse fibroblasts to induced pluripotent stem cells (Vazquez-Martin et al.).

MAINTENANCE

· Inhibits proliferation of mesenchymal stem cells (de Meester et al.).

CANCER RESEARCH

· Delays tumor onset in PTEN-deficient mice (Huang et al.).

METABOLISM

· Inhibits fatty acid synthesis in primary rat hepatocytes and lowers blood glucose in Sprague Dawley rats (Cool et al.).