Protein / target

3',5'-cyclic-AMP phosphodiesterase 4A

PDE4AP27815Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
15
Approved medicines
3
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

3',5'-cyclic-AMP phosphodiesterase activity

Strongest disease association

psoriasis

Genetic evidence · score 0.30

Therapeutic maturity

Clinically validated target

15 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

15 approved · 13 in clinical development

3 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes

Subcellular location

Cytoplasm, perinuclear regionCell projection, ruffle membraneCytoplasm, cytosolMembrane
Domains and Gene Ontology detail (15)

Domains & features

PDEase

Gene Ontology

  • Ccytosol
  • Cextrinsic component of membrane
  • Cmembrane
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Cruffle membrane
  • F3',5'-cyclic-AMP phosphodiesterase activity
  • F3',5'-cyclic-GMP phosphodiesterase activity
  • FcAMP binding
  • Fmetal ion binding
  • PcAMP catabolic process
  • PG protein-coupled receptor signaling pathway

886 aa · 98 kDa · 7 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor signaling pathway
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

DISC1AKAP1ALDH7A1PRKACAPRKACGPRKACBARRB1AKAP6ARRB2ADKPDE4A

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

amlexanox
ApprovedInhibitor

Phosphodiesterase 4 inhibitor

Appears in clinical studies involving Airway obstruction, oral mucositis, Obesity, metabolic dysfunction-associated steatotic liver disease

Acts on a complex — shared with PDE4B, PDE4C, PDE4D · 1 of 4 recorded protein targets

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

psoriasis0.30

Genetic · overall 0.64

psoriasis vulgaris0.12

Genetic · overall 0.61

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

asthma0.99

Clinical · overall 0.62

chronic obstructive pulmonary disease0.98

Clinical · overall 0.61

atopic eczema0.98

Clinical · overall 0.60

psoriatic arthritis0.95

Clinical · overall 0.58

Airway obstruction0.95

Clinical · overall 0.58

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

chronic bronchitis0.57

Clinical

coronary artery disorder0.54

Clinical

stroke disorder0.53

Clinical

Show all associations
psoriasis0.64
asthma0.62
chronic obstructive pulmonary disease0.61
psoriasis vulgaris0.61
atopic eczema0.60
psoriatic arthritis0.58
Airway obstruction0.58
chronic bronchitis0.57
coronary artery disorder0.54
stroke disorder0.53

Open Targets ranks 618 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 28 total

OGLEMILASTPhase 2

asthma · asthma · chronic obstructive pulmonary disease

MK-0873Phase 2

psoriasis vulgaris · chronic obstructive pulmonary disease · rheumatoid arthritis

APREMILASTApproval

Oral ulcer · psoriasis · psoriatic arthritis

LOTAMILASTPhase 2

atopic eczema

AMLEXANOXApproval

Airway obstruction · oral mucositis · Obesity

FLAVOXATEApproval

dysuria · Urinary incontinence · Polyuria

DYPHYLLINEApproval

Airway obstruction

DIFAMILASTPhase 3

atopic eczema · Eczematoid dermatitis · atopic eczema

GSK-256066Phase 2

asthma · seasonal allergic rhinitis · chronic obstructive pulmonary disease

IBUDILASTApproval

Castleman disease · Airway obstruction · amyotrophic lateral sclerosis

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · Human Protein Atlas locPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Safety liabilities

regulation of catalytic activity

Clinical trials

3

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

psoriasisWell supported
0.82
agreement 0.720.93
Clinical66%Genetic28%Literature6%RNA expression1%

Open Targets aggregate 0.64 · 4 independent evidence families

asthmaWell supported
0.77
agreement 0.610.92
Clinical88%Literature12%

Open Targets aggregate 0.62 · 2 independent evidence families

chronic obstructive pulmonary diseaseWell supported
0.76
agreement 0.600.92
Clinical89%Literature11%

Open Targets aggregate 0.61 · 2 independent evidence families

psoriasis vulgarisWell supported
0.76
agreement 0.650.87
Clinical84%Genetic14%Literature2%

Open Targets aggregate 0.61 · 3 independent evidence families

atopic eczemaModerately supported
0.74
agreement 0.580.90
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

1

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2024-04-16
    A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024 · 14 citations · Europe PMC · via amlexanox

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.