tomivosertib-eft-508

Description: Tomivosertib (also known as eFT508) is a potent, highly selective, reversible, ATP-competitive and orally bioavailable inhibitor of MNK1 and MNK2 (Mitogen-Activated Protein Kinase Interacting Kinase) with IC50 values of 1-2 nM against both isoforms in enzyme assays. eFT508 inhibits the kinase through a reversible, ATP-competitive mechanism of action. Treatment of tumor cell lines with eFT508 led to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50 = 2-16 nM), consistent with previous findings that phosphorylation of this site is solely dependent upon MNK1/MNK2. In a panel of ca.50 hematological cancers, eFT508 showed anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to eFT508 in TMD8, OCI-Ly3 and HBL1 DLBCL cell lines was associated with dose-dependent decreases in production of pro-inflammatory cytokines including TNFalpha, IL-6, IL-10 and CXCL10.

References: Blood 2015 126:1554

Related CAS #: 1849590-01-7 (free base); 1849590-02-8 (HCl);