Compounds of Plant Origin as AMP-Activated Protein Kinase Activators

ATP Mimetic Attack on the Nucleotide-Binding Domain to Overcome ABC Transporter Mediated Chemoresistance

“…In the cell, AICAR is metabolized to ZMP phosphorylated at the ribose fragment, which interacts with the γ-regulatory subunit of AMP-activated protein kinase (AMPK), which leads to the structural rearrangement of the γ-subunit and AMPK activation. − To make sure that the observed effect is not associated with the activation of AMPK, we used an AMPK activator of another chemical class, C24 (Figure S7), which interacts not with the AMP-binding cavity of the γ-subunit, but with the autoinhibitory domain of AMPK and activates the kinase by a different mechanism . Accordingly, C24 should not affect ATP-dependent efflux.…”