eFT508
Potent MNK1/2 inhibitor / eFT508 is a potent (IC50s = 2.4 nM MNK1; 1.0 nM MNK2) and highly selective inhibitor of the mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2), key regulators of mRNA translation protein eukaryotic initiation factor eIF4E.1 It potently inhibits phosphorylation of eIF4E in multiple solid and hematological tumor lines leading to blockade of pro-inflammatory and pro-tumorigenic cytokine production. eFT508 reversed the aggressive and metastatic characteristics of mouse liver cancer via inhibition of PD-L1 upregulation.2 Displays inhibitory effects in various cancers models including acute myeloid leukemia3, gastric4, and breast5. eFT-508 has also shown efficacy in treating neuropathic pain via the MNK-eIF4E pathway.6,7,8
Biochemicals & reagents
1849590-01-7
Tomivosertib
1) Reich et al. (2018), Structure-based design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition; J.Med.Chem. 61 3516 2) Xu et al. (2019), Translation control of the immune checkpoint in cancer and its therapeutic targeting; Nat. Med. 25 301 3) Suarez et al. (2021), Inhibitory effects of Tomivosertib in acute myeloid leukemia; Oncotarget 12 955 4) Yang et al. (2022), Inhibition MNL-eIF4E-ß-catenin preferentially sensitizes gastric cancer to chemotherapy; Fundam. Clin. Pharmacol. 36 712 5) Yang et al. (2022), Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment; J. Transl. Med. 20 276 6) Megat et al. (2019), Nociceptor Translational Profiling Reveals the Ragulator-Rag GTPase Complex as a Critical Generator of Neuropathic Pain; J. Neurosci. 39 393 7) Shiers et al. (2020), Reversal of peripheral nerve injury-induced neuropathic pain and cognitive dysfunction via genetic and tomivosertib targeting of MNK; Neuropsychopharmacology 45 524 8) Jeevakumar et al. (2020), IL-6 induced upregulation of T-type Ca2+ currents and sensitization of DRG nociceptors is attenuated by MNK inhibition; J. Neurophysiol. 124 274
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TARGET: Kinase -- PATHWAY: MAPK; Protein synthesis -- RESEARCH AREA: Neuroscience -- DISEASE AREA: Cancer; Pain