tomivosertib   Click here for help

GtoPdb Ligand ID: 10167

Synonyms: compound 23 [PMID: 29526098] | eFT-508 | eFT508
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Tomivosertib (eFT508) is an orally active and selective mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) inhibitor that is being developed by eFFECTOR Therapeutics for anti-neoplastic potential [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 114.93
Molecular weight 340.16
XLogP 2.41
No. Lipinski's rules broken 0
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Canonical SMILES Nc1ncnc(c1)Nc1cc(C)c2n(c1=O)C1(CCCCC1)NC2=O
Isomeric SMILES Nc1ncnc(c1)Nc1cc(C)c2n(c1=O)C1(CCCCC1)NC2=O
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)
Bioactivity Comments
Tomivosertib inhibits in vitro eIF4E phosphorylation (at Ser209) with IC50s in the 1.4-22 nM range, but it only shows antiproliferative effects in in vivo models [2]. From kinase selectivity screening data (at 1 μM compound) potential off targets to bear in mind are STK17A (DRAK1) and CLK4 which were the only two kinases in the screening set that were inhibited by ≥60%.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
MAPK interacting serine/threonine kinase 2 Primary target of this compound Hs Inhibitor Inhibition 9.0 pIC50 - 2
pIC50 9.0 (IC50 1x10-9 M) [2]
Description: Biochemical inhibition assay.
MAPK interacting serine/threonine kinase 1 Primary target of this compound Hs Inhibitor Inhibition 8.6 pIC50 - 2
pIC50 8.6 (IC50 2.4x10-9 M) [2]
Description: Biochemical inhibition assay.
serine/threonine kinase 17a Hs Inhibitor Inhibition 6.9 pIC50 - 2
pIC50 6.9 (IC50 1.3x10-7 M) [2]
Description: Biochemical inhibition assay.
CDC like kinase 4 Hs Inhibitor Inhibition 6.1 pIC50 - 2
pIC50 6.1 (IC50 7.9x10-7 M) [2]
Description: Biochemical inhibition assay.