For research use only. Not for therapeutic Use.
Tomivosertib (eFT508) is a potent, highly selective, and orally active MNK1 and MNK2 inhibitor, with IC50s of 1-2 nM against both isoforms. Tomivosertib (eFT508) treatment leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50=2-16 nM) in tumor cell lines[1]. Tomivosertib (eFT508) also dramatically downregulates PD-L1 protein abundance[2].
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[1].
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[1].
| Catalog Number | I002390 |
| CAS Number | 1849590-01-7 |
| Synonyms | 6-[(6-aminopyrimidin-4-yl)amino]-8-methylspiro[2H-imidazo[1,5-a]pyridine-3,1′-cyclohexane]-1,5-dione |
| Molecular Formula | C17H20N6O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C17H20N6O2/c1-10-7-11(21-13-8-12(18)19-9-20-13)16(25)23-14(10)15(24)22-17(23)5-3-2-4-6-17/h7-9H,2-6H2,1H3,(H,22,24)(H3,18,19,20,21) |
| InChIKey | HKTBYUWLRDZAJK-UHFFFAOYSA-N |
| SMILES | CC1=C2C(=O)NC3(N2C(=O)C(=C1)NC4=NC=NC(=C4)N)CCCCC3 |
| Reference | [1]. Kevin R. Webster, et al. eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2015 126:1554. [2]. Xu Y, et al. Translation control of the immune checkpoint in cancer and its therapeutic targeting. Nat Med. 2019 Feb;25(2):301-311. |
