ADORA2A

Adenosine A2A receptor

Score: 0.685 Price: $0.69 Medium Druggability Status: active Wiki: adora2a

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

31

KG EDGES

54

DEBATES

0

3D Protein Structure

🧬 ADORA2A — PDB 3EML Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.57

Clinical Stage

Approved

Target Class

Gpcr

Safety

0.70

Druggability Analysis

Drug Development1.00

Structural Tractability0.95

Target Class0.85

Safety Profile0.70

Key Metrics

PDB Structures:

90

Known Drugs:

12

Approved:

2

In Clinical Trials:

9

Drug Pipeline (12 compounds)

2 Approved · 6 Phase II · 3 Phase I · 1 Discontinued

Therapeutic Areas:

CNS/Neuroscience Cardiovascular Pain Neurodegeneration

Druggability Rationale: ADORA2A demonstrates high druggability for neurodegeneration, with multiple small molecule antagonists already showing clinical validation, particularly in Parkinson's disease contexts. The extensive structural data (90 PDB entries, best resolution 1.7Å) and AlphaFold predictions suggest excellent structural characterization, which facilitates rational drug design. Istradefylline's approval and ongoing clinical trials exploring antagonists like PBF-509 underscore the target's promising potential for modulating neuroinflammatory and neurodegenerative processes.

Mechanism: Small molecule antagonists blocking adenosine A2A receptor signaling

Drug Pipeline (12 compounds)

2 Approved · 6 Phase II · 3 Phase I · 1 Discontinued

Known Drugs:

Istradefylline (approved) — Parkinson's disease

Preladenant (discontinued) — Parkinson's disease

CHEMBL3989695 (approved)

CHEMBL3694769 (phase_1)

CHEMBL3942498 (phase_1)

CHEMBL197669 (phase_1)

CHEMBL1950651 (phase_2)

CHEMBL447664 (phase_2)

Structural Data:

PDB (90) ✓AlphaFold ✓Cryo-EM ✓

3PWH 3QAK 3REY 3RFM 3UZA+85 more

UniProt: C9JFS2

Binding Pocket Analysis:

7TM binding cavity, extracellular loops

🧬 3D Protein Structure

🧬 ADORA2A — PDB 3EML Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

GPCR selectivity should be assessed against related receptor subtypes. Off-target GPCR activity (especially at hERG, muscarinic, and adrenergic receptors) is a common source of clinical adverse effects.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

8

Total Enrollment

3,477

By Phase

PHASE2: 2 · PHASE3: 5 · PHASE4: 1

Istradefylline Effect Protocol on Parkinson's Disease Tremor Completed

PHASE4 NCT05885360 n=27

Parkinson Disease, Tremor

Interventions: Istradefylline Pill

Sponsor: Georgetown University | Started: 2023-01-20

Long Term Study of Istradefylline in Subjects With Moderate to Severe Parkinson's Disease Completed

PHASE3 NCT02610231 n=239

Idiopathic Parkinson's Disease

Interventions: Istradefylline 20 mg or 40 mg

Sponsor: Kyowa Kirin Co., Ltd. | Started: 2015-12

A 12-week Randomized Study to Evaluate Oral Istradefylline in Subjects With Moderate to Severe Parkinson's Disease Completed

PHASE3 NCT01968031 n=613

Idiopathic Parkinson's Disease

Interventions: Istradefylline 40 mg, Istradefylline 20 mg, Placebo

Sponsor: Kyowa Kirin Co., Ltd. | Started: 2013-10

An Extension of Istradefylline in Parkinson's Disease Patients Who Have Completed Studies 6002-EU-007, 6002-US-013 or 60 Completed

PHASE3 NCT00199368 n=1100

Parkinson's Disease

Interventions: Istradefylline ( KW-6002)

Sponsor: Kyowa Kirin, Inc. | Started: 2004-10

A Placebo- and Active Controlled Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease (P04938) Completed

PHASE3 NCT01155466 n=778

Parkinson Disease

Interventions: Preladenant 2 mg tablet, Preladenant 5 mg tablet, Preladenant 10 mg tablet

Sponsor: Merck Sharp & Dohme LLC | Started: 2010-07-14

Placebo Controlled Study of Preladenant in Participants With Moderate to Severe Parkinson's Disease (P07037) Completed

PHASE3 NCT01227265 n=476

Parkinson Disease, Idiopathic Parkinson Disease, Idiopathic Parkinson's Disease

Interventions: Preladenant, Placebo

Sponsor: Merck Sharp & Dohme LLC | Started: 2010-11-19

A Study of Istradefylline (KW-6002) for the Treatment of Parkinson's Disease Completed

PHASE2 NCT00250393 n=64

Parkinson's Disease

Interventions: Istradefylline (KW-6002)

Sponsor: Kyowa Kirin Co., Ltd. | Started: 2005-11

12-Week, Double-Blind, Placebo-Controlled, Randomized Study of the Efficacy of 40 mg/Day KW-6002 in Parkinson's Disease Completed

PHASE2 NCT00456586 n=180

Parkinson's Disease

Interventions: KW-6002 (istradefylline)

Sponsor: Kyowa Kirin, Inc. | Started: 2002-04

Linked Hypotheses (1)

Adenosine-Astrocyte Metabolic Reset0.557

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (2)

ADORA2A → C1Q

ADORA2A → phagocytosis

associated with (1)

ADORA2A → neurodegeneration

co discussed (8)

ADORA2A → ADRA2A

ADORA2A → MTNR1A

ADORA2A → HCRT

ADORA2A → CX3CR1

ADORA2A → BMAL1

...and 3 more

implicated in (1)

ADORA2A → neurodegeneration

interacts with (5)

ADORA2A → BNIP3L

ADORA2A → BCL2

ADORA2A → DRP1

ADORA2A → DNM1L

ADORA2A → BNIP3

participates in (1)

ADORA2A → Astrocyte reactivity signaling

regulates (2)

ADORA2A → BCL2

ADORA2A → OVERVIEW

Debate History (0)

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