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CMLD012612 is an amidino-rocaglate containing a hydroxamate group and is a potent eukaryotic initiation factor 4A (eIF4A) inhibitor. CMLD012612 inhibits cell translation and is cytotoxic to NIH/3T3 cells with an IC₅₀ value of 2 nM. CMLD012612 inhibits eukaryotic translation initiation by modifying the behavior of the RNA helicase (eIF4A) and possesses potent anti-neoplastic activity.

The IC₅₀ of CMLD012612 toward NIH/3T3 cells is 2 nM. The primary mechanism of action of CMLD012612 is dependent on eIF4A1, since eIF4A1em1jp cells are at least 10-fold more resistant than parental NIH/3T3 cells. The sensitivity of eIF4A1em1jp cells to CMLD012612 observed at higher concentrations may be due to the presence of wild-type eIF4A2 in the cells.

CMLD012612 (0.5 mg/kg; intraperitoneal injection; for 3 hours; female C57BL/6 mice) treatment effectively suppresses liver polysomes 3 hours after injection, indicating inhibitory activity toward protein synthesis.
When administered to mice bearing myr-Akt/Em-Myc lymphomas, CMLD012612 (0.2 mg/kg; intraperitoneal injection; daily; for 5 days; female C57BL/6 mice) treatment effectively synergizes with Doxorubicin, leading to complete tumor loss.

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