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Details

Stereochemistry ACHIRAL
Molecular Formula C17H20N6O2
Molecular Weight 340.3797
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOMIVOSERTIB

SMILES

CC1=C2N(C(=O)C(NC3=CC(N)=NC=N3)=C1)C4(CCCCC4)NC2=O

InChI

InChIKey=HKTBYUWLRDZAJK-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C17H20N6O2
Molecular Weight 340.3797
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Tomivosertib (eFT-508) is a dual inhibitor of MAP kinase-interacting kinases (MNK1 and MNK2) thereby controlling translation. It has potent in vivo antitumor activity in models of diffuse large cell B-cell lymphoma and solid tumors. Tomivosertib acts on multiple points in the cancer immunity cycle simultaneously, underscoring its therapeutic potential as both a monotherapy and in combination with existing checkpoint inhibitor treatments. Preclinical studies suggest combining tomivosertib with a checkpoint inhibitor can overcome mechanisms of resistance to checkpoint inhibitors, resulting in enhanced sensitivity to checkpoint inhibitors and a higher response rate. In addition, preclinical data demonstrate that tomivosertib as a single agent promotes antitumor immunity that persists after stopping drug treatment. Tomivosertib is currently being evaluated in Phase 2 clinical trials in solid tumors and lymphoma. Additionally, tomivosertib may be a new therapeutic for neuropathic pain.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
2.4 nM [IC50]
2.4 nM [IC50]

Cmax

ValueDoseCo-administeredAnalytePopulation
0.11 μg/mL
50 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.24 μg/mL
100 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.3 μg/mL
200 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.37 μg/mL
300 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.54 μg/mL
450 mg single, oral
EFT-508 plasma
Homo sapiens
0.46 μg/mL
600 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.15 μg/mL
50 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.23 μg/mL
100 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.46 μg/mL
200 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.4 μg/mL
300 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.49 μg/mL
450 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
0.58 μg/mL
600 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1.5 μg × h/mL
50 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
3.3 μg × h/mL
100 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
3.6 μg × h/mL
200 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
4.7 μg × h/mL
300 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
7.8 μg × h/mL
450 mg single, oral
EFT-508 plasma
Homo sapiens
6.6 μg × h/mL
600 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
1.98 μg × h/mL
50 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
3.3 μg × h/mL
100 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
6 μg × h/mL
200 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
4.6 μg × h/mL
300 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
7.1 μg × h/mL
450 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens
7.5 μg × h/mL
600 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
9.7 h
300 mg 1 times / day multiple, oral
EFT-508 plasma
Homo sapiens

PubMed

Substance Class Chemical
Record UNII
U2H19X4WBV
Record Status Validated (UNII)
Record Version