Target family: Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs) (type: enzyme)
Target: phosphodiesterase 4D

Ligand: 6-Hydroxy-5,7-dimethoxyflavone (Natural product)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.449999809265137 pIC50
Reference (Journal): 6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury.
Published in: Free Radic Biol Med

Ligand: apremilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2014), EMA (2015)
Primary target: yes
Median affinity: 7.480000019073486 pIC50
Reference (Journal): Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity.
Published in: Cell Signal

Ligand: BPN14770 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 6.900000095367432 pIC50
Reference (Journal): Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
Published in: J Med Chem

Ligand: BPN14770 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: yes
Median affinity: 8.130000114440918 pIC50
Reference (Journal): Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
Published in: J Med Chem

Ligand: BPN14770 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: no
Median affinity: 5.989999771118164 pIC50
Reference (Journal): Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
Published in: J Med Chem

Ligand: BPN14770 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Negative
Ligand approved: no
Primary target: yes
Median affinity: 8.109999656677246 pIC50
Reference (Journal): Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
Published in: J Med Chem

Ligand: CBS-3595 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.099999904632568 pIC50
Reference (Journal): Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases.
Published in: J Med Chem

Ligand: CDP840 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.149999618530273 pKi
Reference (Journal): CDP840: a novel inhibitor of PDE-4.
Published in: Cell Biochem Biophys

Ligand: compound 29 [Moslin et al., 2017] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.369999885559082 pIC50
Reference (Journal): Identification of imidazo[1,2-<i>b</i>]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling.
Published in: Medchemcomm

Ligand: compound 3m [PMID: 32603117] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.159999847412109 pIC50
Reference (Journal): Discovery of Novel Selective and Orally Bioavailable Phosphodiesterase-1 Inhibitors for the Efficient Treatment of Idiopathic Pulmonary Fibrosis.
Published in: J Med Chem

Ligand: difamilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: Japan (2021)
Primary target: no
Median affinity: 7.300000190734863 pIC50
Reference (Patent): Oxazole compound and pharmaceutical composition

Ligand: LEO 239652 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.420000076293945 pIC50
Reference (Journal): Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3<i>H</i>-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-<i>a</i>]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel "Dual-Soft" PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis.
Published in: J Med Chem

Ligand: LEO 29102 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.300000190734863 pIC50
Reference (Journal): Discovery and early clinical development of 2-{6-[2-(3,5-dichloro-4-pyridyl)acetyl]-2,3-dimethoxyphenoxy}-N-propylacetamide (LEO 29102), a soft-drug inhibitor of phosphodiesterase 4 for topical treatment of atopic dermatitis.
Published in: J Med Chem

Ligand: MK-0359 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.920000076293945 pIC50
Reference (Journal): L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition.
Published in: Biochem Pharmacol

Ligand: nerandomilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.039999961853027 pIC50
Reference (Journal): BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis.
Published in: Front Pharmacol

Ligand: PDE4 inhibitor 16 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.619999885559082 pIC50
Reference (Journal): Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent.
Published in: J Med Chem

Ligand: Ro20-1724 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.199999809265137 pIC50
Reference (Journal): Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D.
Published in: Biochem Biophys Res Commun

Ligand: rolipram (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.199999809265137 pIC50
Reference (Journal): Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D.
Published in: Biochem Biophys Res Commun

Ligand: RS-25344 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Median affinity: 8.4 pIC50
Reference (Journal): Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors.
Published in: Cell Signal