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SEL201 is a project focused on development of small molecule inhibitors of MNK1 and MNK2
(dual inhibitors). MNK1/2 are activated by various oncogenic signaling pathways and phosphorylate translation initiation factor eIF4E on a conserved serine 209. eIF4E is highly expressed in diverse types of cancer and contributes to the oncogenic transformation both in vitro and in vivo. Inhibition of MNK1/2 is sufficient to block phosphorylation of eIF4E by and its tumorigenic activity.
- Effective in various oncology disorders dependent on the activity of eIF4E
- Differential cytotoxicity under stress condition typical for tumor environment
- Effective in combinations PI3K/mTOR inhibitors to counteract feedback resistance mechanisms
- Secondary indication in autoimmune disorders
- Lack of apparent target mediated toxicities
Currently the project is at the stage of lead optimization. Selvita identified the most potent and selective inhibitors reported in the literature so far. Favorable ADME parameters and PK profile allow rapid target validation in in vivo models.