Protein / target

Adenosine receptor A2a

ADORA2AP29274Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
10
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Type 5 metabotropic glutamate receptor binding

Primary system

Nervous system

Strongest disease association

Parkinson disease

Clinical evidence · score 0.61

Therapeutic maturity

Clinically validated target

10 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

10 approved · 17 in clinical development

30 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

Receptor for adenosine (By similarity). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (62)

Gene Ontology

  • Casymmetric synapse
  • Caxolemma
  • Cdendrite
  • Cglutamatergic synapse
  • Cintermediate filament
  • Cmembrane
  • Cneuronal cell body
  • Cplasma membrane
  • Cpostsynaptic membrane
  • Cpresynaptic active zone
  • Cpresynaptic membrane
  • Falpha-actinin binding

412 aa · 45 kDa

Biological roles

Reactome v97

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

Excitatory neurotransmissionGOSynaptic signallingGOG protein-coupled signallingGOApoptosis & cell deathGOImmune signallingGOTranscriptional regulationGO
View supporting evidence

Excitatory neurotransmission

  • ·glutamatergic synapse
  • ·excitatory postsynaptic potential
  • ·positive regulation of synaptic transmission, glutamatergic
  • ·synaptic transmission, glutamatergic

Synaptic signalling

  • ·asymmetric synapse
  • ·glutamatergic synapse
  • ·postsynaptic membrane
  • ·presynaptic active zone

G protein-coupled signalling

  • ·G protein-coupled adenosine receptor activity
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  • ·G protein-coupled adenosine receptor signaling pathway

Apoptosis & cell death

  • ·apoptotic process
  • ·negative regulation of neuron apoptotic process

Immune signalling

  • ·inflammatory response

Transcriptional regulation

  • ·regulation of DNA-templated transcription
View underlying pathways (4)

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.

DRD2GNASGRM5GNAQCNR1GNALNTRK2ADORA2BGNB1POMCADORA2A

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.

Adenosine
ApprovedAgonist

Adenosine receptor agonist

Appears in clinical studies involving paroxysmal tachycardia, Wolff-Parkinson-White syndrome, cardiovascular disorder, Paroxysmal supraventricular tachycardia

Acts on a complex — shared with ADORA1, ADORA2B, ADORA3 · 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.

Highest-confidence therapeutic associations

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

migraine disorder0.99

Clinical · overall 0.61

asthma0.99

Clinical · overall 0.61

paroxysmal tachycardia0.97

Clinical · overall 0.59

Parkinson disease0.96

Clinical · overall 0.61

Apnea0.94

Clinical · overall 0.58

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Wolff-Parkinson-White syndrome0.56

Clinical

Pain0.56

Clinical

Airway obstruction0.55

Clinical

Headache0.54

Clinical

neurodegenerative disease0.53

Pathway

Show all associations
Parkinson disease0.61
migraine disorder0.61
asthma0.61
paroxysmal tachycardia0.59
Apnea0.58
Wolff-Parkinson-White syndrome0.56
Pain0.56
Airway obstruction0.55
Headache0.54
neurodegenerative disease0.53

Open Targets ranks 957 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 · 27 total

REGADENOSONApproval

cardiovascular disorder · COVID-19 · sickle cell disease

UK432097Phase 2

chronic obstructive pulmonary disease

SONEDENOSONPhase 2

diabetic foot

THEOPHYLLINEApproval

asthma · chronic bronchitis · chronic obstructive pulmonary disease

REGADENOSON ANHYDROUSPhase 2

acute chest syndrome · sickle cell disease

PENTOXIFYLLINEApproval

cardiovascular disorder · intermittent vascular claudication · liver failure

PBF-509Phase 1 2

non-small cell lung carcinoma

VIPADENANTPhase 2

Parkinson disease · Parkinson disease

ISTRADEFYLLINEApproval

Parkinson disease · Parkinson disease · Parkinson disease

APADENOSONPhase 3

coronary artery disorder

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Small Molecule Binder

Safety liabilities

decreased blood pressureantiinflammationadverse eventsdecreased platelet aggregationarousaldecreased platelet aggregationneuroprotective effectstremorsinsomniaadverse events or adverse eventsincreased plasma renin activitynervousness (tremors, agitation)

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.

Show remaining trials (24)

COMPLETED · via Adenosine · NCT00944970

COMPLETED · via Adenosine · NCT00944294

COMPLETED · via Adenosine · NCT03557385

COMPLETED · via Adenosine · NCT03032965

COMPLETED · via Adenosine · NCT01234870

RECRUITING · via Adenosine · NCT06578234

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.

Parkinson diseaseWell supported
0.76
agreement 0.600.91
Clinical84%Literature16%

Open Targets aggregate 0.61 · 2 independent evidence families

asthmaWell supported
0.75
agreement 0.620.89
Clinical94%Literature5%RNA expression1%

Open Targets aggregate 0.61 · 3 independent evidence families

migraine disorderWell supported
0.75
agreement 0.600.91
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

paroxysmal tachycardiaModerately supported
0.72
agreement 0.560.89
Clinical100%

Open Targets aggregate 0.59 · 1 independent evidence family

ApneaModerately supported
0.71
agreement 0.560.87
Clinical98%Literature2%

Open Targets aggregate 0.58 · 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

30

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 publication2025-10-11
    Adenosine Receptors in Neuroinflammation and Neurodegeneration.

    Cells · 2025 · 2 citations · Europe PMC · via Adenosine

  2. New publication2025-01-01
    REDIportal: toward an integrated view of the A-to-I editing.

    Nucleic acids research · 2025 · 16 citations · Europe PMC · via Adenosine

  3. New publication2024-12-27
    Advances in A-to-I RNA editing in cancer.

    Molecular cancer · 2024 · 17 citations · Europe PMC · via Adenosine

  4. New publication2024-11-28
    Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling.

    Nature communications · 2024 · 16 citations · Europe PMC · via Adenosine

  5. New publication2024-10-05
    Astrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice.

    Nature communications · 2024 · 15 citations · Europe PMC · via Adenosine

  6. New publication2024-09-01
    WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury.

    International journal of surgery (London, England) · 2024 · 41 citations · Europe PMC · via Adenosine

  7. New publication2024-06-18
    Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024 · 17 citations · Europe PMC · via Adenosine

  8. New publication2024-05-21
    Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

    Nature communications · 2024 · 50 citations · Europe PMC · via Adenosine

  9. New publication2024-03-18
    Adenosine and Cortical Plasticity.

    The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025 · 1 citation · Europe PMC · via Adenosine

  10. New publication2024-02-16
    Programmable RNA N<sup>6</sup>-methyladenosine editing with CRISPR/dCas13a in plants.

    Plant biotechnology journal · 2024 · 19 citations · Europe PMC · via Adenosine

  11. New publication2023-11-08
    m<sup>1</sup>A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration.

    Nature · 2023 · 60 citations · Europe PMC · via Adenosine

  12. New publication2023-10-23
    Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice.

    Genome biology · 2023 · 21 citations · Europe PMC · via Adenosine

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.