rocaglamide a

Rocaglamide A is a natural **small-molecule rocaglate/flavagline** isolated from Aglaia species that exhibits potent antineoplastic, antimetastatic, and immunomodulatory activities, and is being investigated preclinically as an anticancer agent rather than used as an approved drug.[5][3][6] It acts primarily as a selective inhibitor of cap-dependent protein translation in tumor cells by binding prohibitin 1 and 2 and functionally targeting the eIF4A-dependent translation machinery, thereby suppressing synthesis of oncogenic and survival proteins; this leads to cell-cycle arrest through Cdc25A degradation via ATM/ATR–Chk1/Chk2 activation, inhibition of Ras–CRaf–MEK–ERK signaling, inactivation of HSF1 with upregulation of TXNIP and reduced glucose uptake, and downregulation of anti-apoptotic factors such as Mcl‑1, c‑FLIP, and XIAP.[5][1][2][3][6][13] Rocaglamide A additionally inhibits NF‑κB activation in T cells, modulates p38 and JNK MAPK pathways to promote apoptosis, suppresses RhoA/Rac1/Cdc42-driven migration and invasion of cancer cells, and can both protect normal hematopoietic cells from DNA-damage–induced apoptosis by limiting p53 translation and enhance certain antitumor immune functions such as NK cell–mediated killing depending on context.[3][6][7][9][10][11] It has demonstrated strong in vivo antitumor activity and oral bioavailability in multiple xenograft and patient-derived xenograft models, including pancreatic cancer, malignant peripheral nerve sheath tumor, and pediatric sarcomas, but remains at the experimental stage without established clinical developers or commercial manufacturers.[3][4][5]

Other names

rocaglamideRoc-A(-)-rocaglamideNSC326408NSC-326408NSC 326408flavagline