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Protein / target

cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A

Encoded byPDE3AQ14432Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
17
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

3',5'-cyclic-nucleotide phosphodiesterase

Strongest disease association

Coronary Artery Disease

Via encoding gene PDE3A · Genetic evidence · score 0.77

Therapeutic position

Established drug target

Small molecules

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 overview

Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

View complete UniProt function annotation

Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099)

Subcellular location

MembraneCytoplasm, cytosol
Domains and Gene Ontology detail (22)

Domains & features

PDEase

Gene Ontology

  • Ccytosol
  • Cmembrane
  • F3',5'-cGMP-inhibited cyclic-nucleotide phosphodiesterase activity
  • F3',5'-cyclic-AMP phosphodiesterase activity
  • F3',5'-cyclic-GMP phosphodiesterase activity
  • F3',5'-cyclic-nucleotide phosphodiesterase activity
  • Festrogen binding
  • Fmetal ion binding
  • Fnuclear estrogen receptor activity
  • Papoptotic signaling pathway
  • Pcellular response to cGMP
  • Pcellular response to transforming growth factor beta stimulus

1141 aa · 125 kDa

Biological roles

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

Lipid & lipoprotein metabolismGOG protein-coupled signallingGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·lipid metabolic process

G protein-coupled signalling

  • ·G protein-coupled receptor signaling pathway
  • ·negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling…

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

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Thrombosis1 medicine

17 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

cilostazol
Narrow target profileApprovedInhibitor

Phosphodiesterase 3A inhibitor

Indicated for Thrombosis

Direct interaction with this protein · Only this protein recorded as a target

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PDE3A

Gene-level evidence surfaced through the gene PDE3A that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Coronary Artery Disease
0.93Well supported

Genetic evidence dominant · Open Targets 0.67

Cardiovascular Diseases
0.90Well supported

Clinical evidence dominant · Open Targets 0.66

Stroke
0.88Well supported

Clinical evidence dominant · Open Targets 0.63

Heart Failure
0.80Well supported

Clinical evidence dominant · Open Targets 0.58

Asthma
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
Coronary Artery DiseaseWell supported
0.93
agreement 0.821.00
Genetic53%Clinical47%Literature1%

Open Targets aggregate 0.67 · 3 independent evidence families

Cardiovascular DiseasesWell supported
0.90
agreement 0.791.00
Clinical50%Genetic49%Literature1%

Open Targets aggregate 0.66 · 3 independent evidence families

StrokeWell supported
0.88
agreement 0.770.98
Clinical50%Genetic48%Literature2%

Open Targets aggregate 0.63 · 3 independent evidence families

Heart FailureWell supported
0.80
agreement 0.690.91
Clinical58%Genetic40%Literature2%

Open Targets aggregate 0.58 · 3 independent evidence families

AsthmaModerately supported
0.74
agreement 0.590.90
Clinical99%Literature1%

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 per-type scores above show the calculation.

Show all associations
Coronary Artery Disease0.67
Cardiovascular Diseases0.66
Stroke0.63
Asthma0.60
Heart Failure0.58
Pulmonary Disease, Chronic Obstructive0.54

Drug development

18 compounds recorded · 17 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
INAMRINONEApproval
MILRINONEApproval
K-134Phase 2
ANAGRELIDE HYDROCHLORIDEApproval
ENOXIMONEApproval
LEVOSIMENDANApproval
PENTOXIFYLLINEApproval
ENSIFENTRINEApproval
OXTRIPHYLLINEApproval
THEOPHYLLINEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot sigp or tmhmm and human protein atlas loc) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

thrombocytopaeniaBowes et al. (2012)thrombocytopeniaUrban et al. (2012)increased heart rateLynch et al. (2017)ventricular arrhythmiaLynch et al. (2017)hypotensionUrban et al. (2012)tachycardiaUrban et al. (2012)decreased platelet aggregationLynch et al. (2017)ventricular arrhythmiasUrban et al. (2012)decreased blood pressureLynch et al. (2017)ventricular arrhythmiaBowes et al. (2012)increased heart rateBowes et al. (2012)decreased female fertilityLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

NOT_YET_RECRUITING · via cilostazol · NCT07174414

RECRUITING · via cilostazol · NCT06202755

RECRUITING · via cilostazol · NCT06196047

RECRUITING · via cilostazol · NCT04753970

TERMINATED · via cilostazol · NCT02374957

COMPLETED · via cilostazol · NCT01995370

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Safety communication2014-12-11

    Drug Safety Update: Cilostazol (Pletal): risks of cardiovascular and bleeding events

    mhra · safety · mhra · via cilostazol

  2. New publication2011-01-01
    Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial.

    Journal of the American College of Cardiology · 2011 · 150 citations · Europe PMC · via cilostazol

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.