A2A receptor

Target id: 19

Nomenclature: A2A receptor

Family: Adenosine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for A2A receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 412 22q11.23 ADORA2A adenosine A2a receptor 39,66,100
Mouse 7 410 10 Adora2a adenosine A2a receptor 79
Rat 7 410 20p12 Adora2a adenosine A2a receptor 18
Previous and Unofficial Names
RDC8 | A2-AR | adenosine receptor A2a
Database Links
Specialist databases
GPCRDB aa2ar_human (Hs), aa2ar_mouse (Mm), aa2ar_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Human A2A adenosine receptor bound to an antagonist
PDB Id:  4EIY
Ligand:  ZM-241385
Resolution:  1.8Å
Species:  Human
References:  74
Image of receptor 3D structure from RCSB PDB
Description:  A2A receptor (thermostabilised) bound to its natural ligand adenosine
PDB Id:  2YDO
Ligand:  adenosine   This ligand is endogenous
Resolution:  3.0Å
Species:  Human
References:  68
Image of receptor 3D structure from RCSB PDB
Description:  Thermostabilised human A2A receptor with NECA bound
PDB Id:  2YDV
Ligand:  NECA
Resolution:  2.6Å
Species:  Human
References:  67
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of stabilized A2A adenosine receptor A2AR-StaR2-bRIL in complex with PSB36
PDB Id:  5N2R
Ligand:  PSB36
Resolution:  2.8Å
Species:  Human
References:  16
Natural/Endogenous Ligands
adenosine

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]CGS 21680 Hs Full agonist 7.7 – 7.8 pKd 50,133
pKd 7.7 – 7.8 (Kd 2.2x10-8 – 1.6x10-8 M) [50,133]
[3H]NECA Hs Full agonist 7.7 pKd 60
pKd 7.7 [60]
apadenoson Hs Agonist 9.3 pKi 99
pKi 9.3 (Ki 5x10-10 M) [99]
(R,S)-PHPNECA Hs Full agonist 8.5 pKi 132
pKi 8.5 [132]
UK-432,097 Hs Agonist 8.3 pKi 136
pKi 8.3 [136]
2-hexynyl-NECA Hs Full agonist 8.2 – 8.3 pKi 28,62,132
pKi 8.2 – 8.3 [28,62,132]
compound 4g [PMID: 22220592] Hs Agonist 8.1 pKi 20
pKi 8.1 (Ki 7.76x10-9 M) [20]
NECA Rn Agonist 8.0 pKi 76
pKi 8.0 (Ki 9.7x10-9 M) [76]
NECA Hs Full agonist 6.9 – 8.7 pKi 10,28,43,57,62,137
pKi 6.9 – 8.7 [10,28,43,57,62,137]
CGS 21680 Rn Agonist 7.7 pKi 73
pKi 7.7 (Ki 1.9x10-8 M) [73]
CGS 21680 Hs Full agonist 6.7 – 8.1 pKi 10,28,43,49,57,60,62,93
pKi 6.7 – 8.1 (Ki 1.99x10-7 – 7.94x10-9 M) [10,28,43,49,57,60,62,93]
2-chloroadenosine Rn Agonist 7.1 pKi 24
pKi 7.1 (Ki 7.6x10-8 M) [24]
CV-1808 Hs Full agonist 7.1 pKi 28,62
pKi 7.1 [28,62]
adenosine Rn Agonist 6.8 pKi 137
pKi 6.8 (Ki 1.5x10-7 M) [137]
2-chloroadenosine Hs Full agonist 6.7 – 6.8 pKi 57,62
pKi 6.7 – 6.8 [57,62]
TCPA Hs Agonist 6.7 pKi 7
pKi 6.7 (Ki 2.1x10-7 M) [7]
(R)-PIA Rn Agonist 6.7 pKi 24
pKi 6.7 (Ki 2.2x10-7 M) [24]
binodenoson Hs Agonist 6.6 pKi 49
pKi 6.6 (Ki 2.7x10-7 M) [49]
regadenoson Hs Agonist 6.5 pKi 49
pKi 6.5 (Ki 2.9x10-7 M) [49]
adenosine Hs Agonist 6.5 pKi 35-36,137
pKi 6.5 (Ki 3.1x10-7 M) [35-36,137]
CGS 24012 Hs Full agonist 6.4 pKi 57
pKi 6.4 [57]
N(6)-cyclohexyladenosine Rn Agonist 6.3 pKi 24
pKi 6.3 (Ki 4.6x10-7 M) [24]
Cl-IB-MECA Rn Agonist 6.3 pKi 73
pKi 6.3 (Ki 4.7x10-7 M) [73]
PENECA Hs Full agonist 6.2 pKi 132
pKi 6.2 [132]
cyclopentyladenosine Hs Full agonist 6.1 pKi 43,49,60
pKi 6.1 [43,49,60]
(R)-PIA Hs Full agonist 6.0 – 6.2 pKi 28,43,57,60,62
pKi 6.0 – 6.2 [28,43,57,60,62]
CCPA Rn Agonist 6.0 pKi 73
pKi 6.0 (Ki 9.5x10-7 M) [73]
cyclopentyladenosine Rn Agonist 6.0 pKi 73
pKi 6.0 (Ki 9.5x10-7 M) [73]
MRS3558 Rn Agonist 6.0 pKi 73
pKi 6.0 (Ki 1.08x10-6 M) [73]
piclidenoson Hs Full agonist 5.6 – 6.3 pKi 49,57,60
pKi 5.6 – 6.3 [49,57,60]
HEMADO Hs Agonist 5.9 pKi 61,132
pKi 5.9 (Ki 1.2x10-6 M) [61,132]
N(6)-cyclohexyladenosine Hs Full agonist 5.9 pKi 28,62
pKi 5.9 [28,62]
GR79236 Hs Agonist 5.9 pKi 49
pKi 5.9 (Ki 1.3x10-6 M) [49]
CV-1674 Hs Full agonist 5.8 pKi 62
pKi 5.8 [62]
tecadenoson Pig Agonist 5.6 pKi 49,86
pKi 5.6 (Ki 2.315x10-6 M) [49,86]
MRS3558 Hs Agonist 5.6 pKi 49
pKi 5.6 (Ki 2.33x10-6 M) [49]
CCPA Hs Full agonist 5.6 pKi 49,60
pKi 5.6 [49,60]
metrifudil Hs Full agonist 5.5 pKi 62
pKi 5.5 [62]
AB-MECA Hs Full agonist 5.4 pKi 60
pKi 5.4 [60]
APNEA Hs Full agonist 5.3 pKi 62
pKi 5.3 [62]
Cl-IB-MECA Hs Agonist 5.3 pKi 49
pKi 5.3 (Ki 5.36x10-6 M) [49]
(S)-PIA Hs Full agonist 5.0 – 5.1 pKi 28,60
pKi 5.0 – 5.1 [28,60]
Cl-IB-MECA Mm Agonist ~5.0 pKi 73
pKi ~5.0 (Ki ~1x10-5 M) [73]
BAY 60-6583 Hs Agonist <5.0 pKi 64
pKi <5.0 (Ki >1x10-5 M) [64]
GS9667 Hs Agonist <5.0 pKi 33
pKi <5.0 (Ki >1x10-5 M) [33]
MRS5151 Hs Agonist <5.0 pKi 81
pKi <5.0 (Ki >1x10-5 M) [81]
MRS5151 Mm Agonist <5.0 pKi 81
pKi <5.0 (Ki >1x10-5 M) [81]
MRS3558 Mm Agonist 5.0 pKi 73
pKi 5.0 (Ki 1.04x10-5 M) [73]
View species-specific agonist tables
Agonist Comments
The INN-assigned compound evodenoson is an agonist of the A2A receptor but affinity data is not available.
Note that for tecadenoson, there is inconsistency between the two referenced articles (from the same group) as to the species origin of the ADORA2A used to generate the Ki value which is presented as identical in both articles. We have used the earlier paper as precedent, which indicates the use of the porcine receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]ZM-241385 Rn Antagonist 9.2 pKd 98
pKd 9.2 [98]
[3H]ZM 241385 Hs Antagonist 8.7 – 9.1 pKd 5,42
pKd 8.7 – 9.1 (Kd 1.8x10-9 – 8x10-10 M) [5,42]
[3H]SCH 58261 Hs Antagonist 8.6 – 9.0 pKd 62,96
pKd 8.6 – 9.0 [62,96]
[3H]XAC Hs Antagonist 8.0 pKd 57
pKd 8.0 [57]
SCH442416 Hs Antagonist 8.4 – 10.3 pKi 119,122
pKi 8.4 – 10.3 [119,122]
MRS1093 Hs Antagonist 9.2 pKi 54
pKi 9.2 [54]
preladenant Hs Antagonist 9.1 pKi 85
pKi 9.1 (Ki 9x10-10 M) [85]
ZM-241385 Hs Antagonist 8.8 – 9.1 pKi 96
pKi 8.8 – 9.1 [96]
vipadenant Hs Antagonist 8.9 pKi 44
pKi 8.9 (Ki 1.3x10-9 M) [44]
SCH 58261 Hs Antagonist 8.3 – 9.2 pKi 28,62,96
pKi 8.3 – 9.2 [28,62,96]
xanthine amine congener Hs Antagonist 8.4 – 9.0 pKi 28,60
pKi 8.4 – 9.0 [28,60]
CGS 15943 Hs Antagonist 7.7 – 9.4 pKi 28,57,60,96
pKi 7.7 – 9.4 [28,57,60,96]
istradefylline Rn Antagonist 8.4 – 8.7 pKi 105,118
pKi 8.4 – 8.7 (Ki 4.46x10-9 – 2.2x10-9 M) [105,118]
tozadenant Hs Antagonist 8.3 pKi 25
pKi 8.3 (Ki 5x10-9 M) [25]
ST-1535 Hs Antagonist 8.2 pKi 82
pKi 8.2 (Ki 6.6x10-9 M) [82]
MSX-2 Rn Antagonist 8.1 pKi 87,113
pKi 8.1 (Ki 8.04x10-9 M) [87,113]
MSX-2 Hs Antagonist 7.8 – 8.3 pKi 113
pKi 7.8 – 8.3 (Ki 1.45x10-8 – 5.38x10-9 M) [113]
KF 17837S Hs Antagonist 7.7 pKi 28
pKi 7.7 [28]
istradefylline Hs Antagonist 7.0 – 7.9 pKi 12,37
pKi 7.0 – 7.9 (Ki 9.12x10-8 – 1.2x10-8 M) [12,37]
CSC Rn Antagonist 7.3 pKi 48
pKi 7.3 (Ki 5.4x10-8 M) [48]
DPCPX Hs Antagonist 6.6 – 7.2 pKi 28,60,62,96,135
pKi 6.6 – 7.2 [28,60,62,96,135]
MRE 3008F20 Hs Antagonist 6.8 pKi 49,125-126
pKi 6.8 [49,125-126]
LUF5981 Hs Antagonist 6.7 pKi 12
pKi 6.7 (Ki 1.94x10-7 M) [12]
rolofylline Hs Antagonist 6.2 – 7.0 pKi 55,101
pKi 6.2 – 7.0 (Ki 6.37x10-7 – 1.08x10-7 M) [55,101]
DPCPX Rn Antagonist 6.3 – 6.8 pKi 58,87
pKi 6.3 – 6.8 (Ki 5x10-7 – 1.57x10-7 M) [58,87]
derenofylline Hs Antagonist 6.4 pKi 53
pKi 6.4 (Ki 3.98x10-7 M) [53]
rolofylline Rn Antagonist 6.3 – 6.4 pKi 56,102
pKi 6.3 – 6.4 (Ki 5.1x10-7 – 3.8x10-7 M) [56,102]
KF26777 Hs Antagonist 6.3 pKi 108
pKi 6.3 (Ki 4.7x10-7 M) [108]
MRS1754 Hs Antagonist 6.3 pKi 59
pKi 6.3 (Ki 5.03x10-7 M) [59]
PSB36 Rn Antagonist 6.3 pKi 135
pKi 6.3 (Ki 5.52x10-7 M) [135]
MRS1754 Rn Antagonist 6.2 pKi 59
pKi 6.2 (Ki 6.12x10-7 M) [59]
CPX Hs Antagonist 6.2 pKi 57
pKi 6.2 [57]
ATL802 Hs Antagonist 6.2 pKi 59
pKi 6.2 (Ki 6.54x10-7 M) [59]
CPFPX Rn Antagonist 6.1 pKi 45
pKi 6.1 (Ki 8.12x10-7 M) [45]
CPFPX Hs Antagonist 6.0 pKi 45
pKi 6.0 (Ki 9.4x10-7 M) [45]
PSB36 Hs Antagonist 6.0 pKi 135
pKi 6.0 (Ki 9.8x10-7 M) [135]
MRE 2029F20 Hs Antagonist <6.0 pKi 6
pKi <6.0 (Ki >1x10-6 M) [6]
galangin Hs Antagonist 6.0 pKi 54
pKi 6.0 [54]
LAS38096 Hs Antagonist <6.0 pKi 30,130
pKi <6.0 (Ki >1x10-6 M) [30,130]
FK-453 Hs Antagonist 5.9 pKi 49
pKi 5.9 (Ki 1.3x10-6 M) [49]
PSB-11 Hs Antagonist 5.9 pKi 97
pKi 5.9 (Ki 1.28x10-6 M) [97]
MRS1523 Rn Antagonist 5.7 pKi 73
pKi 5.7 (Ki 2.05x10-6 M) [73]
PSB-11 Rn Antagonist 5.7 pKi 97
pKi 5.7 (Ki 2.1x10-6 M) [97]
tonapofylline Rn Antagonist 5.6 pKi 55
pKi 5.6 (Ki 2.44x10-6 M) [55]
PSB-10 Hs Antagonist 5.6 pKi 97
pKi 5.6 (Ki 2.7x10-6 M) [97]
MRS1041 Hs Antagonist 5.5 pKi 54
pKi 5.5 [54]
MRS1042 Hs Antagonist 5.5 pKi 54
pKi 5.5 [54]
flavone Hs Antagonist 5.5 pKi 54
pKi 5.5 [54]
theophylline Hs Antagonist 5.2 – 5.8 pKi 28,47,60,125
pKi 5.2 – 5.8 [28,47,60,125]
CVT-6883 Hs Antagonist 5.5 pKi 32
pKi 5.5 (Ki 3.28x10-6 M) [32]
MRS1523 Hs Antagonist 5.4 pKi 73
pKi 5.4 (Ki 3.66x10-6 M) [73]
PSB-10 Rn Antagonist 5.2 pKi 89
pKi 5.2 (Ki 6.04x10-6 M) [89]
MRS928 Hs Antagonist 5.2 pKi 54
pKi 5.2 [54]
tonapofylline Hs Antagonist 5.2 pKi 55
pKi 5.2 (Ki 6.41x10-6 M) [55]
caffeine Hs Antagonist 4.6 – 5.6 pKi 2,47,62
pKi 4.6 – 5.6 [2,47,62]
ATL802 Mm Antagonist 5.1 pKi 59
pKi 5.1 (Ki 8.393x10-6 M) [59]
MRS1191 Hs Antagonist <5.0 pKi 73
pKi <5.0 (Ki >1x10-5 M) [73]
MRS1191 Rn Antagonist <5.0 pKi 73
pKi <5.0 (Ki >1x10-5 M) [73]
VUF5574 Rn Antagonist >5.0 pKi 123
pKi >5.0 (Ki <1x10-5 M) [123]
PSB603 Hs Antagonist <5.0 pKi 9
pKi <5.0 (Ki >1x10-5 M) [9]
PSB603 Rn Antagonist <5.0 pKi 9
pKi <5.0 (Ki >1x10-5 M) [9]
MRS1065 Hs Antagonist 4.9 pKi 54
pKi 4.9 [54]
morin Hs Antagonist 4.8 pKi 54
pKi 4.8 [54]
theophylline Rn Antagonist 4.6 – 4.7 pKi 47,88
pKi 4.6 – 4.7 (Ki 2.53x10-5 – 2.2x10-5 M) [47,88]
PSB1115 Rn Antagonist 4.6 pKi 88
pKi 4.6 (Ki 2.4x10-5 M) [88]
MRS1086 Hs Antagonist 4.6 pKi 54
pKi 4.6 [54]
MRS1132 Hs Antagonist 4.6 pKi 54
pKi 4.6 [54]
MRS1066 Hs Antagonist 4.5 pKi 54
pKi 4.5 [54]
caffeine Rn Antagonist 4.3 – 4.5 pKi 23,47,87
pKi 4.3 – 4.5 (Ki 4.8x10-5 – 3.25x10-5 M) [23,47,87]
sakuranetin Hs Antagonist 4.4 pKi 54
pKi 4.4 [54]
visnagin Hs Antagonist 4.4 pKi 54
pKi 4.4 [54]
MRS1084 Hs Antagonist 4.3 pKi 54
pKi 4.3 [54]
MRS923 Hs Antagonist 4.3 pKi 54
pKi 4.3 [54]
MRS1088 Hs Antagonist 4.3 pKi 54
pKi 4.3 [54]
View species-specific antagonist tables
Antagonist Comments
Some istradefylline pKi values are derived from unpublished data (Müller et al.).

The human MSX-2 pKi values are derived either from experiments using recombinant receptors expressed in CHO (the higher pKi) or from native receptors in human brain tissue (the lower pKi).
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  95
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Adenylate cyclase stimulation
Phospholipase C stimulation
Comments:  A2A receptors have also been shown to couple to adenylate cyclase via Golf in the striatum [63]
References:  38
Tissue Distribution
Thymus gland > heart, lung > spleen, leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  100
Brain: caudate nucleus.
Species:  Human
Technique:  Northern blotting.
References:  100
Platelets.
Species:  Human
Technique:  Radioligand binding.
References:  27,124
Jejunum, ileum, colon.
Species:  Human
Technique:  RT-PCR.
References:  17
Heart, lung > kidney, brain.
Species:  Human
Technique:  Northern blotting.
References:  109
Bone marrow-derived mast cells.
Species:  Mouse
Technique: