eFT508

eFT508 (Tomivosertib) is a potent, highly selective, reversible, ATP-competitive, and orally bioavailable MNK1 and MNK2 inhibitor with IC50 of 1-2 nM in enzyme assays; dose-dependently reduces eIF4E phosphorylation at Serine 209 in tumor cell lines with IC50 of 2-16 nM; shows anti-proliferative activity against multiple DLBCL cell lines, decreases the production of pro-inflammatory cytokines including TNFα, IL-6, IL-10 and CXCL10; demonstrates significant anti-tumor activity in human lymphoma xenograft models which harbor activating MyD88 mutations.Blood Cancer Phase 2 Clinical(In Vitro):Tomivosertib (eFT508) reduces eIF4E phosphorylation dose-dependently at serine 209 (IC50=2-16 nM) in tumor cell lines. In a panel of appr 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. Further evaluation Tomivosertib mechanism of action demonstrates that decreased TNFα production correlates with a 2-fold decrease in TNFα mRNA half-life.\n(In Vivo):Tomivosertib (eFT508) shows significant anti-tumor activity in the TMD8 and HBL-1 ABC-DLBCL models, both of which harbor activating MyD88 mutations. Besides, Tomivosertib combines effectively with components of R-CHOP and with novel targeted agents, including PCI-32765 and Venetoclax, in human lymphoma models.