MDL | MFCD31692387 |
---|---|
Molecular Weight | 408.45 |
Molecular Formula | C25H20N4O2 |
SMILES | N#CC1=CC=C(C2=CN=C3C=CC(C4=CC=C(C(N5CCOCC5)=O)C=C4)=CN32)C=C1 |
MNK1 64 nM (IC 50 ) |
MNK2 86 nM (IC 50 ) |
Tinodasertib (ETC-206) inhibits eIF4E phosphorylation in HeLa cell line with an IC 50 of 321 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). The IC 50 s 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 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. Dasatinib at 2.5 mg/kg elicits a tumor growth inhibition (TGI) of 88% with one tumor-free animal. In contrast, 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 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 has moderate terminal elimination half-life (t 1/2 =1.7 h, and 1.77 h for mouse (1 mg/kg, i.v.), mouse (5 mg/kg, p.o.)) [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Solid
Room temperature in continental US; may vary elsewhere.
Powder | -20°C | 3 years |
---|---|---|
4°C | 2 years | |
In solvent | -80°C | 6 months |
-20°C | 1 month |
DMSO : ≥ 50 mg/mL ( 122.41 mM )
* "≥" means soluble, but saturation unknown.
Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
---|
1 mM | 2.4483 mL | 12.2414 mL | 24.4828 mL |
5 mM | 0.4897 mL | 2.4483 mL | 4.8966 mL |
10 mM | 0.2448 mL | 1.2241 mL | 2.4483 mL |