PH-797804

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Synonyms
Status
Molecule Category UNKNOWN
UNII GEL7GRJ3R6
EPA CompTox DTXSID70207342

Structure

InChI Key KCAJXIDMCNPGHZ-UHFFFAOYSA-N
Smiles CNC(=O)c1ccc(C)c(-n2c(C)cc(OCc3ccc(F)cc3F)c(Br)c2=O)c1
InChI
InChI=1S/C22H19BrF2N2O3/c1-12-4-5-14(21(28)26-3)9-18(12)27-13(2)8-19(20(23)22(27)29)30-11-15-6-7-16(24)10-17(15)25/h4-10H,11H2,1-3H3,(H,26,28)

Physicochemical Descriptors

Property Name Value
Molecular Formula C22H19BrF2N2O3
Molecular Weight 477.31
AlogP 4.43
Hydrogen Bond Acceptor 4.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 5.0
Polar Surface Area 60.33
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 30.0

Bioactivity

Mechanism of Action Action Reference
MAP kinase p38 alpha inhibitor INHIBITOR PubMed PubMed
Protein: MAP kinase p38 alpha
Description: Mitogen-activated protein kinase 14
Organism : Homo sapiens
Q16539 ENSG00000112062
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase CMGC protein kinase group CMGC protein kinase MAPK family CMGC protein kinase p38 subfamily
- 1-247 3 3-6 -
Assay Description Organism Bioactivity Reference
Binding affinity to p38alpha None 5.8 nM
Inhibition of p38alpha None 5.8 nM
Inhibition of p38alpha kinase None 2.9 nM
Inhibition of p38alpha kinase-dependent HSP-27 phosphorylation in human U937 cells Homo sapiens 1.05 nM
Antiinflammatory activity in human monocytes assessed as inhibition of LPS-induced TNFalpha production Homo sapiens 3.4 nM
Antiinflammatory activity in human monocytes assessed as inhibition of LPS-induced IL1-beta production Homo sapiens 3.4 nM
Inhibition of p38alpha kinase in human monocytes Homo sapiens 17.4 nM
Antiinflammatory activity in human whole blood assessed as inhibition of LPS-induced TNFalpha production Homo sapiens 85.0 nM
Inhibition of p38beta kinase None 40.0 nM
Antiinflammatory activity in human U937 cells assessed as inhibition of LPS-induced TNFalpha production Homo sapiens 5.9 nM
Inhibition of p38alpha assessed as phosphorylation FITC-labeled Hsp27 after 60 mins by fluorescence based cascade assay None 2.5 nM Inhibition of p38alpha assessed as phosphorylation FITC-labeled Hsp27 after 60 mins by fluorescence based cascade assay None 2.3 nM Inhibition of p38alpha assessed as phosphorylation FITC-labeled Hsp27 after 60 mins by fluorescence based cascade assay None 247.0 nM
Antiinflammatory activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release pretreated for 1 hr before LPS treatment measured after 18 hrs Homo sapiens 15.0 nM Antiinflammatory activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release pretreated for 1 hr before LPS treatment measured after 18 hrs Homo sapiens 3.4 nM
Antiinflammatory activity in fasted Lewis rat assessed as inhibition of LPS-induced TNFalpha production at 5 mg/kg, po administered 4 hrs prior LPS challenge measured after 90 mins by ELISA Rattus norvegicus 95.0 % Antiinflammatory activity in fasted Lewis rat assessed as inhibition of LPS-induced TNFalpha production at 5 mg/kg, po administered 4 hrs prior LPS challenge measured after 90 mins by ELISA Rattus norvegicus 38.0 %
Antiarthritic activity in Lewis rat assessed as inhibition of streptococcal cell wall-induced paw swelling at 2 mg/kg/day, po administered on day 10 of streptococcal cell wall challenge continued until day 21 by plethysmometer Rattus norvegicus 80.0 %
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 102.0 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 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 672.0 nM
Binding affinity to wild type human biotin labelled p38 alpha (9 to 352 residues) expressed in sf21 insect cells SPR analysis Homo sapiens 2.5 nM
Binding affinity to wild type human biotin labelled p38 alpha (9 to 352 residues) expressed in sf21 insect cells assessed as dissociation rate constant by SPR analysis Homo sapiens 2.75 10'-2/s
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 81.49 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 17.5 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -5.054 %
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 -0.22 % 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 -0.29 % 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 -0.22 % 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 -0.29 %

Cross References

Resources Reference
ChEBI 82715
ChEMBL CHEMBL1088751
DrugBank DB07941
FDA SRS GEL7GRJ3R6
Guide to Pharmacology 7818
PDB I45
SureChEMBL SCHEMBL2015676
ZINC ZINC000013980453
CONTENTS