TOMIVOSERTIB

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Synonyms
Status
Molecule Category UNKNOWN
UNII U2H19X4WBV

Structure

InChI Key HKTBYUWLRDZAJK-UHFFFAOYSA-N
Smiles Cc1cc(Nc2cc(N)ncn2)c(=O)n2c1C(=O)NC21CCCCC1
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)

Physicochemical Descriptors

Property Name Value
Molecular Formula C17H20N6O2
Molecular Weight 340.39
AlogP 1.63
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 3.0
Number of Rotational Bond 2.0
Polar Surface Area 114.93
Molecular species NEUTRAL
Aromatic Rings 2.0
Heavy Atoms 25.0

Bioactivity

Mechanism of Action Action Reference
MAP kinase-interacting serine/threonine-protein kinase 1/2 inhibitor INHIBITOR Other ClinicalTrials Other Other
Protein: MAP kinase-interacting serine/threonine-protein kinase 1/2
Description: MAP kinase-interacting serine/threonine-protein kinase 1
Organism : Homo sapiens
Q9BUB5 ENSG00000079277
Protein: MAP kinase-interacting serine/threonine-protein kinase 1/2
Description: MAP kinase-interacting serine/threonine-protein kinase 2
Organism : Homo sapiens
Q9HBH9 ENSG00000099875
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase CAMK protein kinase group CAMK protein kinase DAPK family
- 131 - - -
Enzyme Kinase Protein Kinase CAMK protein kinase group CAMK protein kinase MAPKAPK family CAMK protein kinase MNK subfamily
- 1-2 - 3 88
Enzyme Kinase Protein Kinase CMGC protein kinase group CMGC protein kinase CLK family
- 787 - - -
Assay Description Organism Bioactivity Reference
Inhibition of full length GST-tagged recombinant human MNK1 expressed in insect cells using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay Homo sapiens 2.4 nM
Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay Homo sapiens 1.0 nM
Inhibition of MNK1/2 in human HCT116 cells assessed as decrease in eIF4E phosphorylation at Ser209 after 2 hrs by HTRF assay Homo sapiens 6.0 nM
Inhibition of DRAK1 (unknown origin) Homo sapiens 131.0 nM
Inhibition of CLK4 (unknown origin) Homo sapiens 787.0 nM
In vivo inhibition of MNK1/2 in human TMD8 cells xenografted in NOD SCID mouse assessed as reduction in eIF4E phosphorylation at Ser209 at 1 mg/kg, po qd administered for 14 days measured over 8 hrs post last dose by Western blot method relative to control Mus musculus 80.0 %
In vivo inhibition of MNK1/2 in human TMD8 cells xenografted in NOD SCID mouse assessed as reduction in eIF4E phosphorylation at Ser209 administered as po qd for 14 days measured over 24 hrs post last dose by Western blot method Mus musculus 15.8 nM
IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells). Chlorocebus sabaeus 346.74 nM
Inhibition of recombinant His-tagged MNK2 (unknown origin) using eIF4E-derived peptide as substrate in presence of ATP at Km concentration by ADP-Glo assay Homo sapiens 3.0 nM
Inhibition of recombinant GST-tagged MNK1 (unknown origin) using eIF4E-derived peptide as substrate in presence of ATP at km concentration by ADP-Glo assay Homo sapiens 5.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 2.67 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.01 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.01 %
Antiproliferative activity against human CT26 cells assessed as reduction in cell viability at 20 uM incubated for 72 hrs by MTT assay relative to control Homo sapiens 43.1 %
Antiproliferative activity against human MDA-MB-435 cells assessed as reduction in cell viability at 20 uM incubated for 72 hrs by MTT assay relative to control Homo sapiens 49.2 %
Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability at 20 uM incubated for 72 hrs by MTT assay relative to control Homo sapiens 52.7 %
Antiproliferative activity against human A549 cells assessed as reduction in cell viability incubated at 20 uM for 72 hrs by MTT assay relative to control Homo sapiens 40.6 %
Inhibition of MNK2 (unknown origin) at 100 nM incubated for 60 mins by HTRF assay Homo sapiens 98.8 %
Inhibition of MNK1 (unknown origin) at 100 nM incubated for 60 mins by HTRF assay Homo sapiens 87.8 %
Inhibition of recombinant human N-terminal GST-tagged MNK2 (1 to 465 residues) expressed in baculovirus expression system using TATKSGSTTKNR as substrate preincubated for 10 mins followed by ATP addition and measured after 40 mins by luminescence based assay Homo sapiens 2.1 nM
Inhibition of recombinant human N-terminal DYKDDDDK-tagged MNK1(1 to 424 residues) expressed in baculovirus expression system using TATKSGSTTKNR as substrate preincubated for 10 mins followed by ATP addition and measured after 40 mins by luminescence based assay Homo sapiens 3.3 nM

Cross References

Resources Reference
ChEMBL CHEMBL4073443
DrugBank DB15219
FDA SRS U2H19X4WBV
Guide to Pharmacology 10167
PDB N45
PubChem 118598754
SureChEMBL SCHEMBL17362622
ZINC ZINC000575623807
CONTENTS