ETC-206 是选择性MNK1和MNK2抑制剂，IC50分别为 64 和 86 nM。

ETC-206 is a selective inhibitor of MNK1 and MNK2 (IC50s: 64 nM and 86 nM).

The anti-proliferative effects of ETC-206 are assessed in vitro, using CellTiter-Glo viability assay against 25 hematological cancer cell lines including the K562 cell line that overexpresses eIF4E (K562 o/e eIF4E). ETC-206 inhibits eIF4E phosphorylation in HeLa cell line (IC50: 321 nM). The IC50s are 1.71 μM, 3.36 μM, 3.70 μM, 4.81 μM, 5.13 μM, 5.05 μM, 6.70 μM, 9.76 μM, and 48.8 μM for SU-DHL-6, GK-5, MC 116, P3HR-1, DOHH2, MPC-11, Ramos.2G6.4C10, AHH-1, and K562 o/e eIF4E cells, respectively.

The antitumor effect of ETC-206 is then assessed in a K562 e/o eIF4E mouse xenograft model after oral administration at 25, 50, or 100 mg/kg alone or in combination with a 2.5 mg/kg fixed-dose of Dasatinib throughout the study. ETC-206 with 2.5 mg/kg of Dasatinib not only increases tumor growth inhibition in a dose-dependent manner but, more importantly, leads to 2, 5, and 8 out of 8 tumor-free animals at 25, 50, and 100 mg/kg, respectively. The combination of ETC-206 and Dasatinib inhibits tumor growth at all tested doses, and no weight loss is recorded. Both the combination of ETC-206 and Dasatinib and, on the other hand, the dual MNK1/2 and BCR-ABL1 inhibitors prevent tumor growth in the same mouse xenograft model. ETC-206 alone only yields a maximum TGI of 23% at the highest administered dose of 100 mg/kg, which does not impede tumor growth, and is similar to the nontreated animals. ETC-206 has moderate terminal elimination half-life (t1/2=1.7 h, and 1.77 h for mouse (1 mg/kg, i.v.), mouse (5 mg/kg, p.o.)).

1464151-33-4

C25H20N4O2

408.45

DMSO:50 mg/mL (122.41 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years