TAK-733

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Synonyms
Status
Molecule Category UNKNOWN
UNII 5J61HSP0QJ
EPA CompTox DTXSID20648089

Structure

InChI Key RCLQNICOARASSR-SECBINFHSA-N
Smiles Cn1c(=O)c(F)c(Nc2ccc(I)cc2F)c2c(=O)n(C[C@@H](O)CO)cnc21
InChI
InChI=1S/C17H15F2IN4O4/c1-23-15-12(16(27)24(7-21-15)5-9(26)6-25)14(13(19)17(23)28)22-11-3-2-8(20)4-10(11)18/h2-4,7,9,22,25-26H,5-6H2,1H3/t9-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C17H15F2IN4O4
Molecular Weight 504.23
AlogP 1.07
Hydrogen Bond Acceptor 8.0
Hydrogen Bond Donor 3.0
Number of Rotational Bond 5.0
Polar Surface Area 109.38
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 28.0

Bioactivity

Mechanism of Action Action Reference
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor INHIBITOR PubMed PubMed
Protein: Dual specificity mitogen-activated protein kinase kinase 2
Description: Dual specificity mitogen-activated protein kinase kinase 2
Organism : Homo sapiens
P36507 ENSG00000126934
Protein: Dual specificity mitogen-activated protein kinase kinase 1
Description: Dual specificity mitogen-activated protein kinase kinase 1
Organism : Homo sapiens
Q02750 ENSG00000169032
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE7 family
- 2-7 - - -
Assay Description Organism Bioactivity Reference
Inhibition of MEK1 by IMAP assay None 3.2 nM
Cytotoxicity against human A375 cells after 72 hrs by MTS assay Homo sapiens 3.1 nM
Cytotoxicity against human COLO205 cells after 72 hrs by MTS assay Homo sapiens 2.1 nM
Inhibition of MEK1 (unknown origin) Homo sapiens 1.79 nM
Inhibition of MEK1 in human COLO205 cells Homo sapiens 6.92 nM
Enzyme Assay: The inhibitory properties of compounds relative to MEK1 or MEK2 may be determined using a black 384-well-plate format under the following reaction conditions: 50 mM HEPES pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 1 nM MEK1 or 4 nM MEK2, 25 nM ERK1, 400 μM ATP, 500 nM IPTTPITTYFFFK-5FAM-COOH (FI-Erktide), and 1% DMSO. Reaction product is determined quantitatively by fluorescent polarization using progressive IMAP beads from Molecular Devices. The assay reaction may be initiated as follows: 2 μl of the mixture of 1.5 μM FI-Erktide and 75 nM ERK with 2 μl of inhibitor (2 fold serial dilutions for 11 data points for each inhibitor) containing 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of the mixture of 3 nM MEK1 or 12 nM MEK2 and 1200 μM ATP to initiate the reaction (final enzyme concentration was 1 nM for MEK1 or 4 nM for MEK2). The reaction mixture may then be incubated at room temperature for 22 min, and quenched and developed by addition of 20 μl of 1:200 dilution of progressive IMAP beads (Molecular Devices) in 80% buffer A, 20% bufferB and 0.003% Tween 20. Fluorescence polarization of the resulting reaction mixtures may be measured after a 1 hour incubation at room temperature. Homo sapiens 5.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 21.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. Homo sapiens 20.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -3.57 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 2.82 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -1.707 %
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 -0.24 % 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 -0.27 % 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 -0.27 % 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 -0.24 %

Cross References

Resources Reference
ChEMBL CHEMBL1615025
DrugBank DB12241
FDA SRS 5J61HSP0QJ
Guide to Pharmacology 9911
PDB IZG
PubChem 24963252
SureChEMBL SCHEMBL1528606
ZINC ZINC000043196550
CONTENTS