2-Hydroxy-benzoic acid 2-[[4-(diethylamino)-2-hydroxyphenyl]methylene]hydrazide

General Description

A cell permeable hydrozide that activates AMPK indirectly via a CaMKKβ-dependent pathway similar to resveratrol (Cat. No. 554325), which results in the phosphorylation of Thr-172 on the AMPKα2 subunit. This activator promotes lysosomal amyloid-β degradation in 3 cell lines nearly 40 times more potently than resveratrol with an IC₅₀ of 1-2 μM. Treatment with RSVA314 at 1-3 μM results in a dose-dependent inhibition of the phosphorylation of 3 proteins downstream from mTOR activation including p70S6K, eukaryotic elongation factor 2 kinase (eEF2K), and S6 ribosomal protein, and promotes a robust increase in the phosphorylation of the protein raptor at Ser-792 in western blots. At the same concentrations, it elicits a strong, dose-dependent conversion of the light chain 3 (LC3) protein, a marker involved with autophagy induction, from LC3-I and LC3-II, also in western blots.

Biochem/physiol Actions

RSVA314 is a resveratrol analog that is a potent indirect activator of AMPK (AMP-activated protein kinase). RSVA314 is a potent inhibitor of adipogenesis in vitro in cultured cells and in vivo in mice. Apparently RSVA314 activates AMPK via a mechanism implicating CaMKKβ and LKB1. Also RSVA314 increases intracellular clearance of the amyloidogenic peptide Aβ, the core component of the amyloid plaques.