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Compound Detail

CHEMBL4073443

TOMIVOSERTIB
🧪 Phase II
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🧪 Phase II
Cc1cc(Nc2cc(N)ncn2)c(=O)n2c1C(=O)NC21CCCCC1

Basic Information

ChEMBL ID CHEMBL4073443
Name TOMIVOSERTIB
Phase Phase II
Structure Type MOL
InChI Key HKTBYUWLRDZAJK-UHFFFAOYSA-N

Known Names

Eft 508 EFT-508 Eft508 Tomivosertib
15
Targets
25
Activities
2
Assay Types
8
PK Parameters
20
Publications
4
Known Names
8
Indications
1
Mechanisms

Molecular Properties

340.4
MW (Da)
1.63
ALogP
7
HBA
3
HBD
114.9
PSA (Ų)
0.77
QED
0
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Chemical Probe
USAN Stem -sertib
USAN Year 2018

Extended Properties

Molecular Formula C17H20N6O2
MW 340.39
Aromatic Rings 2
Heavy Atoms 25
NP-Likeness -0.36

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
MAP kinase-interacting serine/threonine-protein kinase 1/2 inhibitor INHIBITOR MAP kinase-interacting serine/threonine-protein kinase 1/2

Indications

Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Neoplasms Neoplasms Prostatic Neoplasms, Castration-Resistant Breast Neoplasms Leukemia, Myeloid, Acute Lymphoma

Activity Summary

IC50 23 meas. best 9.0
Ki 2 meas. best 8.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
MAP kinase-interacting serine/threonine-protein kinase 2
CHEMBL4204
IC50 9.0 8.91 1.0 4
Eukaryotic translation initiation factor 4E
CHEMBL4848
IC50 8.85 8.4467 1.4 3
MAP kinase-interacting serine/threonine-protein kinase 1
CHEMBL4718
IC50 8.72 8.61 1.9 4
MAP kinase-interacting serine/threonine-protein kinase 2
CHEMBL4204
Ki 8.52 8.52 3.0 1
MAP kinase-interacting serine/threonine-protein kinase 1
CHEMBL4718
Ki 8.3 8.3 5.0 1
MAP kinase-interacting serine/threonine-protein kinase 1/2
CHEMBL3883293
IC50 8.22 8.22 6.0 1
Mus musculus
CHEMBL375
IC50 7.8 7.8 15.8 1
Serine/threonine-protein kinase 17A
CHEMBL4525
IC50 6.88 6.88 131.0 1
SARS-CoV-2
CHEMBL4303835
IC50 6.46 6.46 346.7 1
Dual specificity protein kinase CLK4
CHEMBL4203
IC50 6.1 6.1 787.0 1
TMD8
CHEMBL4296503
IC50 5.6 5.6 2530.0 1
LN-18
CHEMBL4296458
IC50 5.2 5.2 6270.0 1
DOHH-2
CHEMBL2366181
IC50 5.2 5.2 6300.0 1
K562
CHEMBL385
IC50 4.87 4.87 13540.0 1
MV4-11
CHEMBL613835
IC50 4.84 4.84 14490.0 1
PC-3
CHEMBL390
IC50 4.53 4.53 29400.0 1
MDA-MB-231
CHEMBL400
IC50 4.35 4.35 45000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 231.0 - Chlorocebus sabaeus
F 79.0 % Mus musculus
F 85.0 % Rattus norvegicus
F 100.0 % Canis lupus familiaris
F 24.0 % Macaca fascicularis
T1/2 2.0 hr Homo sapiens
T1/2 2.0 hr Canis lupus familiaris
T1/2 2.0 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
MAP kinase-interacting serine/threonine-protein kinase 2 IC50 = 1.0 nM 9.0 Inhibition of Mnk2 (unknown origin) 34533957
MAP kinase-interacting serine/threonine-protein kinase 2 IC50 = 1.0 nM 9.0 Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed... 29526098
MAP kinase-interacting serine/threonine-protein kinase 2 IC50 = 1.1 nM 8.96 Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate ... 38564512
Eukaryotic translation initiation factor 4E IC50 = 1.4 nM 8.85 Inhibition of Ser 209 phosphorylation of eIF4E (unknown origin) 34533957
MAP kinase-interacting serine/threonine-protein kinase 1 IC50 = 1.9 nM 8.72 Inhibition of recombinant MNK1 (unknown origin) using TATKSGSTTKNR as substrate ... 38564512
MAP kinase-interacting serine/threonine-protein kinase 2 IC50 = 2.1 nM 8.68 Inhibition of recombinant human N-terminal GST-tagged MNK2 (1 to 465 residues) e... 30824167
MAP kinase-interacting serine/threonine-protein kinase 1 IC50 = 2.4 nM 8.62 Inhibition of full length GST-tagged recombinant human MNK1 expressed in insect ... 29526098
MAP kinase-interacting serine/threonine-protein kinase 1 IC50 = 2.4 nM 8.62 Inhibition of Mnk1 (unknown origin) 34533957
MAP kinase-interacting serine/threonine-protein kinase 2 Ki = 3.0 nM 8.52 Inhibition of recombinant His-tagged MNK2 (unknown origin) using eIF4E-derived p... 31362920
MAP kinase-interacting serine/threonine-protein kinase 1 IC50 = 3.3 nM 8.48 Inhibition of recombinant human N-terminal DYKDDDDK-tagged MNK1(1 to 424 residue... 30824167
MAP kinase-interacting serine/threonine-protein kinase 1 Ki = 5.0 nM 8.3 Inhibition of recombinant GST-tagged MNK1 (unknown origin) using eIF4E-derived p... 31362920
Eukaryotic translation initiation factor 4E IC50 = 5.4 nM 8.27 Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incuba... 38564512
Eukaryotic translation initiation factor 4E IC50 = 6.0 nM 8.22 Inhibition of phosphorylation of eIF4E (unknown origin) in HCT-116 cells 34533957
MAP kinase-interacting serine/threonine-protein kinase 1/2 IC50 = 6.0 nM 8.22 Inhibition of MNK1/2 in human HCT116 cells assessed as decrease in eIF4E phospho... 29526098
Mus musculus IC50 = 15.8 nM 7.8 In vivo inhibition of MNK1/2 in human TMD8 cells xenografted in NOD SCID mouse a... 29526098
Serine/threonine-protein kinase 17A IC50 = 131.0 nM 6.88 Inhibition of DRAK1 (unknown origin) 29526098
SARS-CoV-2 IC50 = 346.74 nM 6.46 IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h ... 32353859
Dual specificity protein kinase CLK4 IC50 = 787.0 nM 6.1 Inhibition of CLK4 (unknown origin) 29526098
TMD8 IC50 = 2530.0 nM 5.6 Antiproliferative activity against human TMD8 cells assessed as reduction in cel... 30824167
DOHH-2 IC50 = 6300.0 nM 5.2 Antiproliferative activity against human DOHH-2 cells assessed as inhibition of ... 38564512

Literature References

PubMed DOI Target Context # Activities
29526098 10.1021/acs.jmedchem.7b01795 Unchecked 15
29526098 10.1021/acs.jmedchem.7b01795 MAP kinase-interacting serine/threonine-protein kinase 1/2 8
- 10.6019/CHEMBL5303304 U2OS 8
29526098 10.1021/acs.jmedchem.7b01795 Mus musculus 7
29526098 10.1021/acs.jmedchem.7b01795 ADMET 5
29526098 10.1021/acs.jmedchem.7b01795 Plasma 5
- 10.6019/CHEMBL5303304 Fibroblast 4
29526098 10.1021/acs.jmedchem.7b01795 TMD8 3
35417652 10.1021/acs.jmedchem.1c01941 MAP kinase-interacting serine/threonine-protein kinase 1 3
29526098 10.1021/acs.jmedchem.7b01795 Liver 3
38564512 10.1021/acs.jmedchem.3c02008 ADMET 3
32353859 10.1038/s41586-020-2286-9 SARS-CoV-2 3
31362920 10.1016/j.bmcl.2019.07.043 MAP kinase-interacting serine/threonine-protein kinase 1 2
32353859 10.1038/s41586-020-2286-9 Vero C1008 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
30824167 10.1016/j.bmc.2019.02.007 MAP kinase-interacting serine/threonine-protein kinase 1 2
35417652 10.1021/acs.jmedchem.1c01941 Unchecked 2
34533957 10.1021/acs.jmedchem.1c00368 Eukaryotic translation initiation factor 4E 2
- 10.6019/CHEMBL5303304 HEK-293T 2
30824167 10.1016/j.bmc.2019.02.007 MAP kinase-interacting serine/threonine-protein kinase 2 2

Data from ChEMBL 36 via Core Engine