GSK-256066

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Synonyms
Status
Molecule Category UNKNOWN
UNII 2D6GK059SR
EPA CompTox DTXSID30230090

Structure

InChI Key JFHROPTYMMSOLG-UHFFFAOYSA-N
Smiles COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)N(C)C)c4)cc23)c1
InChI
InChI=1S/C27H26N4O5S/c1-16-11-21(37(34,35)20-10-5-7-17(12-20)27(33)31(2)3)14-22-24(16)29-15-23(26(28)32)25(22)30-18-8-6-9-19(13-18)36-4/h5-15H,1-4H3,(H2,28,32)(H,29,30)

Physicochemical Descriptors

Property Name Value
Molecular Formula C27H26N4O5S
Molecular Weight 518.6
AlogP 3.93
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 7.0
Polar Surface Area 131.69
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 37.0

Bioactivity

Mechanism of Action Action Reference
Phosphodiesterase 4 inhibitor INHIBITOR PubMed PubMed PubMed
Protein: Phosphodiesterase 4
Description: cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Organism : Homo sapiens
P27815 ENSG00000065989
Protein: Phosphodiesterase 4
Description: cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Organism : Homo sapiens
Q07343 ENSG00000184588
Protein: Phosphodiesterase 4
Description: cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Organism : Homo sapiens
Q08493 ENSG00000105650
Protein: Phosphodiesterase 4
Description: cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Organism : Homo sapiens
Q08499 ENSG00000113448
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4A
- 0 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4B
- 0 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4C
- 0 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4D
- 0 - - -
Assay Description Organism Bioactivity Reference
Inhibition of human recombinant PDE4B by scintillation proximity assay Homo sapiens 0.007943 nM
Antiinflammatory activity in human PBMC assessed as inhibition of LPS-induced TNFalpha production Homo sapiens 0.01 nM
Antiinflammatory activity in human whole blood assessed as inhibition of LPS-induced TNFalpha production Homo sapiens 39.81 nM
Inhibition of His-tagged catalytic domain Trypanosoma brucei brucei PDEB1 expressed in baculovirus infected insect Sf21 cells at 10 uM Trypanosoma brucei 50.0 %
Inhibition of human recombinant PDE4B using [3H]cAMP by packard topcount scintillation counting analysis Homo sapiens 0.01 nM
Antiinflammatory activity in human PBMC assessed as inhibition of LPS-induced TNFalpha production after 20 hrs by fluorescence linked immunosorbant assay Homo sapiens 0.003162 nM
Antiinflammatory activity in human whole blood assessed as inhibition of LPS-induced TNFalpha production after 20 hrs by ELISA Homo sapiens 0.3162 nM
Antiinflammatory activity in rat whole blood assessed as inhibition of LPS-induced TNFalpha production after 20 hrs by ELISA Rattus norvegicus 0.2512 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 1.45 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -2.54 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 4.946 %
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 0.16 % 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 0.31 % 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 0.16 % 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 0.31 %
Inhibition of human PDE4 expressed in Saccharomyces cerevisiae preincubated for 30 mins followed by cAMP substrate addition Homo sapiens 0.0032 nM
Inhibition of late allergic response in atopic asthmatic patient assessed as reduction in minimum FEV1 level at 87.5 ug administered once daily via inhalation for 7 days followed by allergen challenge relative to placebo Homo sapiens 26.2 %
Inhibition of late allergic response in atopic asthmatic patient assessed as reduction in weighted mean FEV1 level at 87.5 ug administered once daily via inhalation for 7 days followed by allergen challenge relative to placebo Homo sapiens 34.3 %
Inhibition of early allergic response in atopic asthmatic patient assessed as reduction in minimum FEV1 level at 87.5 ug administered once daily via inhalation for 7 days followed by allergen challenge relative to placebo Homo sapiens 40.9 %
Inhibition of early allergic response in atopic asthmatic patient assessed as reduction in weighted mean FEV1 level at 87.5 ug administered once daily via inhalation for 7 days followed by allergen challenge relative to placebo Homo sapiens 57.2 %

Cross References

Resources Reference
ChEMBL CHEMBL570015
DrugBank DB12137
FDA SRS 2D6GK059SR
PDB 066
PubChem 9827968
SureChEMBL SCHEMBL1148649
ZINC ZINC000006717510
CONTENTS