CR-1-31-B, a synthetic rocaglate, acts as a highly potent inhibitor of eIF4A. By disrupting the interaction between eIF4A and RNA, it effectively obstructs the initiation phase of protein synthesis. Specifically, CR-1-31-B interferes with the association between Plasmodium falciparum eIF4A (PfeIF4A) and RNA. Additionally, CR-1-31-B induces apoptosis in neuroblastoma and gallbladder cancer cells [4].

CR-1-31-B (100 nM; 24 hours) inhibits MUC1-C translation in EGF-stimulated MCF-10A cells and decreases MUC1-C abundance in MDA-MB-468 breast cancer cells. It sensitizes gallbladder cancer cells to TRAIL-mediated apoptosis by downregulating c-FLIP at the translational level. Neuroblastoma (NB) cell lines show decreased viability, increased apoptosis, and altered cell cycle distribution when treated with CR-1-31-B (24-72 hours), clamping eIF4A and eIF4F onto mRNA to block translation. Additionally, CR-1-31-B (100 nM; 5 hours) enhances reverse glutamine metabolism in pancreatic cancer cells. In viability assays, SH-SY5Y cells and Kelly cells treated with concentrations of 0.1-100 nM for 24-72 hours exhibit significant decreases in viability, with IC50 values of 20 nM for SH-SY5Y and 4 nM for Kelly cells at 48 hours. Apoptosis analysis reveals that CR-1-31-B induces apoptosis in SH-SY5Y cells (10, 20, 50 nM) and Kelly cells (1, 5, 10 nM) over 24-72 hours.

CR-1-31-B, administered intraperitoneally (IP) at a dosage of 2 mg/kg in 60 μL of olive oil once every two days over 28 days, effectively reduces growth and induces TRAIL-mediated apoptosis in gallbladder cancer cells (GBC) within a BALB/c nude mouse model[2]. Additionally, at a lower dosage of 0.2 mg/kg IP daily for 7 days in a murine orthotopic transplant model of pancreatic ductal adenocarcinoma, CR-1-31-B significantly inhibits protein synthesis and tumor growth in pancreatic cancers[5].