Tomivosertib (eFT508) is a potent and highly selective MNK1 and MNK2 inhibitor with an IC50 value of 1-2 nM.

MNK1:1-2 nM, MNK2:1-2 nM

Tomivosertib has a half-maximal inhibitory concentration (IC50) of 1-2 nM against both MNK isoforms in enzyme assays and inhibits the kinase through a reversible, ATP-competitive mechanism of action. Treatment of tumor cell lines with Tomivosertib leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50 = 2-16 nM). In a panel of ~50 hematological cancers, Tomivosertib shows anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to Tomivosertib in TMD8, OCI-Ly3 and HBL1 DLBCL cell lines is associated with dose-dependent decreases in production of pro-inflammatory cytokines including TNFα, IL-6, IL-10 and CXCL10[1].

eFT508 is well-tolerated and shows efficacy against MyD88-mutant DLBCL models in vivo. Significant anti-tumor activity of eFT508 is observed in the TMD8 and HBL-1 ABC-DLBCL models(subcutaneous human lymphoma xenograft models), both of which harbor activating MyD88 mutations[1].

TMD8 cells are treated with the indicated concentrations of eFT508 for 24 h. Cell lysates are subjected to m7-GTP Sepharose pull-down and bound proteins are analyzed by immunoblotting with the indicated antibodies. (Only for Reference)

H2O: <1 mg/mL

DMSO: 11 mg/mL (32.32 mM), Sonication is recommended.

Ethanol: <1 mg/mL