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

Ligand: 6-Hydroxy-5,7-dimethoxyflavone (Natural product)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.119999885559082 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: 7.849999904632568 pIC50
Reference (Journal): Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity.
Published in: Cell Signal

Ligand: CDP840 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.010000228881836 pKi
Reference (Journal): CDP840: a novel inhibitor of PDE-4.
Published in: Cell Biochem Biophys

Ligand: ensifentrine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.829999923706055 pIC50
Reference (Journal): The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one].
Published in: J Pharmacol Exp Ther

Ligand: ibudilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Primary target: yes
Median affinity: 7.269999980926514 pIC50
Reference (Journal): Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
Published in: J Med Chem

Ligand: lenrispodun (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.800000190734863 pIC50
Reference (Journal): Discovery of Potent and Selective Inhibitors of Phosphodiesterase 1 for the Treatment of Cognitive Impairment Associated with Neurodegenerative and Neuropsychiatric Diseases.
Published in: J Med Chem

Ligand: MK-0359 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.800000190734863 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: MK-0873 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.220000267028809 pIC50
Reference (Journal): Optimization and structure-activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: identification of MK-0873, a potent and effective PDE4 inhibitor.
Published in: Bioorg Med Chem Lett

Ligand: nerandomilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.610000133514404 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: piclamilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.819999694824219 pKi
Reference (Journal): Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues.
Published in: J Med Chem

Ligand: revamilast (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.569999694824219 pIC50
Reference (Patent): Novel heterocyclic compounds useful for the treatment of inflammatory and allergic disorders.

Ligand: Ro20-1724 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.5 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: 9 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: 7.2 pIC50
Reference (Journal): Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors.
Published in: Cell Signal

Ligand: YM976 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Median affinity: 8.3 pIC50
Reference (Journal): A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity.
Published in: J Pharmacol Exp Ther