didesmethylrocaglamide

Didesmethylrocaglamide is a naturally occurring derivative of rocaglamide, classified as a cyclopenta[b]benzofuran lignan and part of the rocaglamide family of anti-cancer phytochemicals. It is isolated from plants in the Aglaia genus. Didesmethylrocaglamide exhibits potent antitumor activity, primarily through inhibition of protein synthesis in tumor cells. Its mechanism involves inhibition of prohibitin 1 (PHB1) and prohibitin 2 (PHB2), which are essential for cancer cell proliferation and are implicated in the Ras-mediated CRaf-MEK-ERK signaling pathway that phosphorylates eIF4E, a key factor for initiating protein synthesis. Additionally, it acts as an inhibitor of eukaryotic initiation factor 4A (eIF4A), another critical component for translation initiation. These actions result in downregulation of short-lived proteins involved in cell cycle regulation (such as Cdc25A), promotion of apoptosis via activation of pro-apoptotic proteins p38 and JNK, inhibition of anti-apoptotic Mcl-1 protein, and impairment of glucose uptake by increasing TXNIP expression[1][3][6]. Didesmethylrocaglamide has demonstrated strong growth-inhibitory effects against various cancer cell lines but is not currently approved or marketed for any indication.

Other names

DDR