ETC-206 is an inhibitor of MAPK-interacting serine/threonine kinase 1 (MKNK1) and MKNK2 (IC50s = 0.064 and 0.086 ?M, respectively).1 It is selective for MKNK1 and MKNK2 over a panel of 104 kinases at 1 ?M. ETC-206 inhibits phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) in HeLa cells (IC50 = 0.321 ?M). In vivo, ETC-206 enhances tumor growth inhibition induced by dasatinib in a K562 mouse xenograft model. It also prevents weight gain in a mouse model of high-fat diet-induced obesity when administered at a dose of 100 mg/kg.2
1.Yang, H., Chennamaneni, L.R., Ho, M.W.T., et al.Optimization of selective mitogen-activated protein kinase interacting kinases 1 and 2 inhibitors for the treatment of blast crisis leukemiaJ. Med. Chem.61(10)4348-4369(2018) 2.Sandeman, L.Y., Kang, W.X., Wang, X., et al.Disabling MNK protein kinases promotes oxidative metabolism and protects against diet-induced obesityMol. Metab.42101054(2020)