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| Cas No.: | 1464151-33-4 |
| Chemical Name: | 4-(6-(4-(morpholine-4-carbonyl)phenyl)imidazo[1,2-a]pyridin-3-yl)benzonitrile |
| Synonyms: | ETC206;ETC 206;ETC-1907206 |
| SMILES: | N#CC1C=CC(C2N3C(C=CC(=C3)C3C=CC(C(=O)N4CCOCC4)=CC=3)=NC=2)=CC=1 |
| Formula: | C25H20N4O2 |
| M.Wt: | 408.452 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Publication: | [1]. Yang H, et al. Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia. J Med Chem. 2018 May 24;61(10):4348-4369. |
| Description: | ETC-206 is a selective MNK1 and MNK2 inhibitor with IC50s of 64 nM and 86 nM, respectively. |
| Target: | MNK1:64 nM (IC50) MNK2:86 nM (IC50) |
| In Vivo: | 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 (t1/2=1.7 h, and 1.77 h for mouse (1 mg/kg, i.v.), mouse (5 mg/kg, p.o.))[1]. |
| In Vitro: | ETC-206 inhibits eIF4E phosphorylation in HeLa cell line with an IC50 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 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[1]. |
| Cell Assay: | 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 IC50s are in general in the micromolar range[1]. |
| Animal Administration: | Mice[1] CD-1 female mice (6-8 weeks old) are weighed, and those selected for dosing are 24±2 g. Three mice are randomly grouped per time point. Mice are administered a single dose of 1 mg/kg of ETC-206 via tail vein injection or a single dose of 5 mg/kg of ETC-206 via oral gavage. The volume of injection for intravenous (i.v.) and oral (p.o.) administration is 4 mL/kg and 8 mL/kg, respectively[1]. |
| References: | [1]. Yang H, et al. Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia. J Med Chem. 2018 May 24;61(10):4348-4369. |
MSDS
COA
| LOT NO. | DOWNLOAD |
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| 2018-0101 |
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| 2018-0101 |
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| 2018-0101 |
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