A-769662 CAS NO.844499-71-4

         A-769662 is equally potent in activating the baculovirus expressed α1,β1,γ1 recombinant isoform of AMPK (EC₅₀=0.7 μM). A-769662 and A-592107 activate AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC₅₀s. EC₅₀s determined for A-769662 using partially purified AMPK extracts from rat heart, rat muscle, or human embryonic kidney cells (HEKs) are 2.2 μM, 1.9 μM, or 1.1 μM, respectively^[1]. A-769662 activates endogenous AMPK in LKB1-expressing (HEK293) and LKB1-deficient (CCL13) cells. A-769662 allosterically activates AMPK complexes containing γ1 harboring a substitution of arginine residue 298 to glycine (R298G). A-769662 inhibits dephosphorylation of Thr-172 in the mutant γ1-containing complexes to a similar degree as seen in the wild-type complexes^[2]. A769662 (300 μM) has toxic effects on MEF cells. A769662 reversibly inhibits the proteasomal activity^[3].