APREMILAST

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Trade Names
Synonyms
Status
Molecule Category UNKNOWN
ATC L04AA32
UNII UP7QBP99PN

Structure

InChI Key IMOZEMNVLZVGJZ-QGZVFWFLSA-N
Smiles CCOc1cc([C@@H](CS(C)(=O)=O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC
InChI
InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C22H24N2O7S
Molecular Weight 460.51
AlogP 2.43
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 8.0
Polar Surface Area 119.08
Molecular species NEUTRAL
Aromatic Rings 2.0
Heavy Atoms 32.0

Bioactivity

Mechanism of Action Action Reference
Phosphodiesterase 4 inhibitor INHIBITOR DailyMed
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
- 74-110 - - 8-91
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4B
- 24-74 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4C
- 74-110 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4D
- 33-540 - - -
Assay Description Organism Bioactivity Reference
Inhibition of human PDE4 Homo sapiens 74.0 nM
Inhibition of TNFalpha production in LPS-stimulated human PBMC preincubated before LPS challenge measured after 4 hrs by enzyme immunoassay Homo sapiens 77.0 nM
Inhibition of TNFalpha production in LPS-stimulated human whole blood preincubated before LPS challenge measured after 4 hrs by enzyme immunoassay Homo sapiens 110.0 nM
Inhibition of recombinant human PDE4B2 expressed in African green monkey COS7 cells using cAMP as substrate Homo sapiens 30.0 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 5.54 %
Inhibition of PDE4D (unknown origin) Homo sapiens 33.0 nM
Inhibition of recombinant N-terminal GST-tagged full length human PDE4A1A expressed in Sf9 cells using cAMP as substrate at 0.1xIC50 incubated for 60 mins by fluorescence plate reader analysis Homo sapiens 13.0 %
Inhibition of recombinant N-terminal GST tagged human PDE4A4B (2-end aa) expressed in Sf9 cells using FAM-cAMP as substrate at 0.1xIC50 incubated for 60 mins by fluorescence plate reader analysis Homo sapiens 8.0 %
Inhibition of PDE4B (unknown origin) Homo sapiens 27.0 nM
Inhibition of recombinant N-terminal GST-tagged full length human PDE4A1A expressed in Sf9 cells using cAMP as substrate at 1xIC50 incubated for 60 mins by fluorescence plate reader analysis Homo sapiens 58.0 %
Inhibition of recombinant N-terminal GST tagged human PDE4A4B (2-end aa) expressed in Sf9 cells using FAM-cAMP as substrate at 1xIC50 incubated for 60 mins by fluorescence plate reader analysis Homo sapiens 57.0 %
Inhibition of recombinant N-terminal GST-tagged full length human PDE4A1A expressed in Sf9 cells using cAMP as substrate at 10xIC50 incubated for 60 mins by fluorescence plate reader analysis Homo sapiens 89.0 %
Inhibition of recombinant N-terminal GST tagged human PDE4A4B (2-end aa) expressed in Sf9 cells using FAM-cAMP as substrate at 10xIC50 incubated for 60 mins by fluorescence plate reader analysis Homo sapiens 91.0 %
Inhibition of recombinant human wild-type His6-tagged PDE4D7 UCR1 domain (S129 residues) expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay Homo sapiens 32.0 nM
Inhibition of recombinant human His6-tagged PDE4B1 UCR1 S133D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay Homo sapiens 24.0 nM
Inhibition of recombinant human His6-tagged PDE4D7 UCR1 S129D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay Homo sapiens 26.0 nM
Inhibition of recombinant human His6-tagged PDE4D3 UCR1 S54D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay Homo sapiens 23.0 nM
Inhibition of recombinant human His6-tagged PDE4D2 expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay Homo sapiens 35.0 nM
Inhibition of recombinant human His6-tagged PDE4D UCR2 deletion mutant catalytic domain expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay Homo sapiens 21.0 nM
Inhibition of PDE4D (unknown origin) using cAMP as substrate Homo sapiens 74.0 nM
Inhibition of PDE4 in human PBMC assessed as reduction in LPS-stimulated TNFalpha production Homo sapiens 110.0 nM
Inhibition of PDE4D2 (unknown origin) Homo sapiens 540.0 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 13.15 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -0.6639 %
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 0.02 % 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 0.06 % 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 0.02 % 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 0.06 %
Inhibition of human PDE4D catalytic domain (86 to 413 residues) expressed in Escherichia coli BL21 (DE3) cells using [3H]cAMP as substrate measured after 30 mins by scintillation proximity assay Homo sapiens 47.6 nM
Inhibition of human PDE4B using [3H]cAMP as substrate incubated for 5 mins followed by substrate addition and measured after 10 mins by scintillation proximity assay Homo sapiens 74.0 nM
Inhibition of PDE-4 in human PBMC assessed as LPS-induced TNFalpha production incubated for 15 mins followed by LPS stimulation and measured after 18 hrs by ELISA relative to control Homo sapiens 77.0 nM
Inhibition of PDE4 (unknown origin) Homo sapiens 74.0 nM

Cross References

Resources Reference
ChEBI 78540
ChEMBL CHEMBL514800
DrugBank DB05676
DrugCentral 4829
FDA SRS UP7QBP99PN
Guide to Pharmacology 7372
KEGG D08860
PDB A9L
PubChem 11561674
SureChEMBL SCHEMBL302992
ZINC ZINC000030691736
CONTENTS