Fig. 12.

Inhibition of protein synthesis by rocaglamides. The Ras-Raf-MEK-ERK and the PI3K-AKT-mTOR pathways play a central role in regulation of cap-dependent translation by activation of the eukaryotic translation initiation factor 4E (eIF4E). eIF4E binds to the 5′ cap structure and assembles eIF4G and eIF4A to initiate translation. Rocaglamide congeners 23 and 35 directly bind to and inhibit eIF4A function. Rocaglamides 1, 4, 7 and 50 block the MEK-REK pathway and inhibit eIF4E cap binding activity