CMLD012612 

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^[1].

eIF4A^[1]

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^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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^[1].
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^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

559.61

C₃₁H₃₃N₃O₇

2368900-35-8

Solid

White to light yellow

CC1=N[C@@]2(O)[C@H](C(N(OC)C)=O)[C@@H](C3=CC=CC=C3)[C@]4(C5=CC=C(OC)C=C5)OC6=C(C(OC)=CC(OC)=C6)[C@@]42N1

Room temperature in continental US; may vary elsewhere.

• [1]. Chu J, et al. Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors. Cell Chem Biol. 2019 Nov 21;26(11):1586-1593.  [Content Brief]