Tomivosertib (eFT-508) (C09-1074-427)

InformationTomivosertib (eFT-508) Tomivosertib (eFT-508) is a potent and selective MNK1/2 inhibitor with IC50s of 2.4 nM and 1 nM, respectively. It potentially results in decreased tumor cell proliferation and tumor growth. Tomivosertib (eFT-508) inhibits eIF4E phosphorylation and dramatically downregulates PD-L1 protein abundance.TargetsMNK2 (Cell-free assay); MNK1 (Cell-free assay) 1 nM; 2.4 nMIn vitroeFT508 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 eFT508 leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50 = 2-16 nM). In a panel of ~50 hematological cancers, eFT508 shows anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to eFT508 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.In vivoeFT508 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.Cell Research(from reference)Cell lines：TMD8 cells Concentrations：0.01, 0.1, 1, 3, 10 μM Incubation Time：24 h. Specifications and Purity: 97%. Molecular Formula: C17H20N6O2. Molecular Weight: 340.38. PubChem CID: 118598754. Isomeric SMILES: CC1=C2C(=O)NC3(N2C(=O)C(=C1)NC4=NC=NC(=C4)N)CCCCC3.