Top ▲

A2A receptor

Click here for help

Target id: 19

Nomenclature: A2A receptor

Family: Adenosine receptors

Gene and Protein Information Click here for help
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 43,72,108
Mouse 7 410 10 C1 Adora2a adenosine A2a receptor 85
Rat 7 410 20p12 Adora2a adenosine A2a receptor 22
Previous and Unofficial Names Click here for help
RDC8 | A2-AR | adenosine receptor A2a
Database Links Click here for help
Specialist databases
GPCRDB aa2ar_human (Hs), aa2ar_mouse (Mm), aa2ar_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
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:  80
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:  74
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:  73
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:  20
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein.
PDB Id:  6GDG
Ligand:  NECA
Resolution:  3.8Å
Species:  Human
References:  47
Natural/Endogenous Ligands Click here for help
adenosine

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]CGS 21680 Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.7 – 7.8 pKd 56,142
pKd 7.7 – 7.8 (Kd 2.2x10-8 – 1.6x10-8 M) [56,142]
[3H]NECA Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.7 pKd 67
pKd 7.7 [67]
apadenoson Small molecule or natural product Click here for species-specific activity table Hs Agonist 9.3 pKi 107
pKi 9.3 (Ki 5x10-10 M) [107]
(R,S)-PHPNECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.5 pKi 141
pKi 8.5 [141]
2-hexynyl-NECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.2 – 8.3 pKi 32,68,141
pKi 8.2 – 8.3 [32,68,141]
compound 4g [PMID: 22220592] Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Agonist 8.1 pKi 24
pKi 8.1 (Ki 7.76x10-9 M) [24]
NECA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 8.0 pKi 82
pKi 8.0 (Ki 9.7x10-9 M) [82]
UK-432,097 Small molecule or natural product Ligand has a PDB structure Hs Agonist 7.7 – 8.3 pKi 50,147
pKi 7.7 – 8.3 [50,147]
NECA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.9 – 8.7 pKi 14,32,45,63,68,148
pKi 6.9 – 8.7 [14,32,45,63,68,148]
CGS 21680 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 7.7 pKi 79
pKi 7.7 (Ki 1.9x10-8 M) [79]
CGS 21680 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.7 – 8.1 pKi 14,32,45,55,63,67-68,101
pKi 6.7 – 8.1 (Ki 1.99x10-7 – 7.94x10-9 M) [14,32,45,55,63,67-68,101]
2-chloroadenosine Small molecule or natural product Click here for species-specific activity table Rn Agonist 7.1 pKi 28
pKi 7.1 (Ki 7.6x10-8 M) [28]
CV-1808 Small molecule or natural product Hs Full agonist 7.1 pKi 32,68
pKi 7.1 [32,68]
adenosine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 6.8 pKi 148
pKi 6.8 (Ki 1.5x10-7 M) [148]
2-chloroadenosine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.7 – 6.8 pKi 63,68
pKi 6.7 – 6.8 [63,68]
TCPA Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pKi 10
pKi 6.7 (Ki 2.1x10-7 M) [10]
(R)-PIA Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.7 pKi 28
pKi 6.7 (Ki 2.2x10-7 M) [28]
binodenoson Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 pKi 55
pKi 6.6 (Ki 2.7x10-7 M) [55]
regadenoson Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 6.5 pKi 55
pKi 6.5 (Ki 2.9x10-7 M) [55]
adenosine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 6.5 pKi 39-40,148
pKi 6.5 (Ki 3.1x10-7 M) [39-40,148]
CGS 24012 Small molecule or natural product Hs Full agonist 6.4 pKi 63
pKi 6.4 [63]
N(6)-cyclohexyladenosine Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.3 pKi 28
pKi 6.3 (Ki 4.6x10-7 M) [28]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.3 pKi 79
pKi 6.3 (Ki 4.7x10-7 M) [79]
PENECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 pKi 141
pKi 6.2 [141]
cyclopentyladenosine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.1 pKi 45,55,67
pKi 6.1 [45,55,67]
(R)-PIA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 – 6.2 pKi 32,45,63,67-68
pKi 6.0 – 6.2 [32,45,63,67-68]
CCPA Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.0 pKi 79
pKi 6.0 (Ki 9.5x10-7 M) [79]
cyclopentyladenosine Small molecule or natural product Ligand has a PDB structure Rn Agonist 6.0 pKi 79
pKi 6.0 (Ki 9.5x10-7 M) [79]
MRS3558 Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.0 pKi 79
pKi 6.0 (Ki 1.08x10-6 M) [79]
piclidenoson Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 5.6 – 6.3 pKi 55,63,67
pKi 5.6 – 6.3 [55,63,67]
HEMADO Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.9 pKi 66,141
pKi 5.9 (Ki 1.2x10-6 M) [66,141]
N(6)-cyclohexyladenosine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.9 pKi 32,68
pKi 5.9 [32,68]
GR79236 Small molecule or natural product Hs Agonist 5.9 pKi 55
pKi 5.9 (Ki 1.3x10-6 M) [55]
CV-1674 Small molecule or natural product Hs Full agonist 5.8 pKi 68
pKi 5.8 [68]
tecadenoson Small molecule or natural product Click here for species-specific activity table Pig Agonist 5.6 pKi 55,93
pKi 5.6 (Ki 2.315x10-6 M) [55,93]
MRS3558 Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.6 pKi 55
pKi 5.6 (Ki 2.33x10-6 M) [55]
CCPA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 pKi 55,67
pKi 5.6 [55,67]
metrifudil Small molecule or natural product Hs Full agonist 5.5 pKi 68
pKi 5.5 [68]
AB-MECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.4 pKi 67
pKi 5.4 [67]
APNEA Small molecule or natural product Hs Full agonist 5.3 pKi 68
pKi 5.3 [68]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.3 pKi 55
pKi 5.3 (Ki 5.36x10-6 M) [55]
(S)-PIA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.0 – 5.1 pKi 32,67
pKi 5.0 – 5.1 [32,67]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Mm Agonist ~5.0 pKi 79
pKi ~5.0 (Ki ~1x10-5 M) [79]
BAY 60-6583 Small molecule or natural product Click here for species-specific activity table Hs Agonist <5.0 pKi 70
pKi <5.0 (Ki >1x10-5 M) [70]
GS9667 Small molecule or natural product Click here for species-specific activity table Hs Agonist <5.0 pKi 37
pKi <5.0 (Ki >1x10-5 M) [37]
MRS5151 Small molecule or natural product Click here for species-specific activity table Hs Agonist <5.0 pKi 88
pKi <5.0 (Ki >1x10-5 M) [88]
MRS5151 Small molecule or natural product Click here for species-specific activity table Mm Agonist <5.0 pKi 88
pKi <5.0 (Ki >1x10-5 M) [88]
MRS3558 Small molecule or natural product Click here for species-specific activity table Mm Agonist 5.0 pKi 79
pKi 5.0 (Ki 1.04x10-5 M) [79]
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 Value Parameter Reference
[125I]ZM-241385 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.2 pKd 106
pKd 9.2 [106]
[3H]ZM 241385 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.7 – 9.1 pKd 4,44
pKd 8.7 – 9.1 (Kd 1.8x10-9 – 8x10-10 M) [4,44]
[3H]SCH 58261 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.6 – 9.0 pKd 68,104
pKd 8.6 – 9.0 [68,104]
[3H]XAC Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 8.0 pKd 63
pKd 8.0 [63]
SCH442416 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 – 10.3 pKi 128,131
pKi 8.4 – 10.3 [128,131]
MRS1093 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.2 pKi 60
pKi 9.2 [60]
preladenant Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.1 pKi 92
pKi 9.1 (Ki 9x10-10 M) [92]
ZM-241385 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.8 – 9.1 pKi 104
pKi 8.8 – 9.1 [104]
vipadenant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 8.9 pKi 48
pKi 8.9 (Ki 1.3x10-9 M) [48]
AZD4635 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 8.8 pKi 12
pKi 8.8 (Ki 1.7x10-9 M) [12]
Description: Binding affinity of AZD4635 determined in a radioligand binding competition assays with membranes prepared from HEK-293-T cells stably expressing human A2AR.
SCH 58261 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 9.2 pKi 32,68,104
pKi 8.3 – 9.2 [32,68,104]
xanthine amine congener Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 – 9.0 pKi 32,67
pKi 8.4 – 9.0 [32,67]
CGS 15943 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 – 9.4 pKi 32,63,67,104
pKi 7.7 – 9.4 [32,63,67,104]
istradefylline Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.4 – 8.7 pKi 113,127
pKi 8.4 – 8.7 (Ki 4.46x10-9 – 2.2x10-9 M) [113,127]
tozadenant Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Antagonist 8.3 pKi 29
pKi 8.3 (Ki 5x10-9 M) [29]
ST-1535 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 89
pKi 8.2 (Ki 6.6x10-9 M) [89]
MSX-2 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.1 pKi 94,121
pKi 8.1 (Ki 8.04x10-9 M) [94,121]
MSX-2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.8 – 8.3 pKi 121
pKi 7.8 – 8.3 (Ki 1.45x10-8 – 5.38x10-9 M) [121]
PBF-509 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 7.6 – 7.9 pKi 49,87
pKi 7.9 (Ki 1.2x10-8 M) [49,87]
Description: Determined in a competitive radioligand binding assay using membranes prepared from HeLa cells expressing human A2A receptor.
pKi 7.6 (Ki 2.5x10-8 M) [49,87]
Description: Antagonism of rolipram-induced cAMP accummulation in CHO cells expressing the human A2A receptor, as measured using a proprietary enzymeimmunoassay.
KF 17837S Small molecule or natural product Hs Antagonist 7.7 pKi 32
pKi 7.7 [32]
istradefylline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.0 – 7.9 pKi 16,41
pKi 7.0 – 7.9 (Ki 9.12x10-8 – 1.2x10-8 M) [16,41]
CSC Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.3 pKi 54
pKi 7.3 (Ki 5.4x10-8 M) [54]
compound 10 [PMID: 31306001] Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 pKi 9
pKi 7.2 (Ki 6.8x10-8 M) [9]
Description: Binding affinity calculated by measuring displacement of specific [3H]ZM24138 binding at hA2AARs expressed in CHO cells.
mefloquine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 pKi 144
pKi 7.0 (Ki 1.04x10-7 M) [144]
Description: Binding affinity determined by displacement of [3H]-CGS21680 from human A2A receptors by increasing concentrations of racemic mefloquine.
DPCPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 7.2 pKi 32,67-68,104,145
pKi 6.6 – 7.2 [32,67-68,104,145]
MRE 3008F20 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 pKi 55,134-135
pKi 6.8 [55,134-135]
LUF5981 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 pKi 16
pKi 6.7 (Ki 1.94x10-7 M) [16]
rolofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 – 7.0 pKi 61,109
pKi 6.2 – 7.0 (Ki 6.37x10-7 – 1.08x10-7 M) [61,109]
DPCPX Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.3 – 6.8 pKi 64,94
pKi 6.3 – 6.8 (Ki 5x10-7 – 1.57x10-7 M) [64,94]
derenofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 59
pKi 6.4 (Ki 3.98x10-7 M) [59]
rolofylline Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.3 – 6.4 pKi 62,110
pKi 6.3 – 6.4 (Ki 5.1x10-7 – 3.8x10-7 M) [62,110]
KF26777 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.3 pKi 116
pKi 6.3 (Ki 4.7x10-7 M) [116]
MRS1754 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.3 pKi 65
pKi 6.3 (Ki 5.03x10-7 M) [65]
PSB36 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.3 pKi 145
pKi 6.3 (Ki 5.52x10-7 M) [145]
MRS1754 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.2 pKi 65
pKi 6.2 (Ki 6.12x10-7 M) [65]
CPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 63
pKi 6.2 [63]
ATL802 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 65
pKi 6.2 (Ki 6.54x10-7 M) [65]
CPFPX Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.1 pKi 51
pKi 6.1 (Ki 8.12x10-7 M) [51]
CPFPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 51
pKi 6.0 (Ki 9.4x10-7 M) [51]
PSB36 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 145
pKi 6.0 (Ki 9.8x10-7 M) [145]
MRE 2029F20 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <6.0 pKi 7
pKi <6.0 (Ki >1x10-6 M) [7]
galangin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 60
pKi 6.0 [60]
LAS38096 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <6.0 pKi 34,139
pKi <6.0 (Ki >1x10-6 M) [34,139]
LUF7602 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 149
pKi 5.9 (Ki 1.259x10-6 M) [149]
Description: Affinity determined from the displacement of specific [3H]ZM241385 binding on HEK293 cell membranes stably expressing human adenosine A2A receptors at 25 °C during 2 h of incubation.
FK-453 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 55
pKi 5.9 (Ki 1.3x10-6 M) [55]
PSB-11 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 105
pKi 5.9 (Ki 1.28x10-6 M) [105]
MRS1523 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.7 pKi 79
pKi 5.7 (Ki 2.05x10-6 M) [79]
PSB-11 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.7 pKi 105
pKi 5.7 (Ki 2.1x10-6 M) [105]
tonapofylline Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.6 pKi 61
pKi 5.6 (Ki 2.44x10-6 M) [61]
PSB-10 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pKi 105
pKi 5.6 (Ki 2.7x10-6 M) [105]
MRS1041 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 pKi 60
pKi 5.5 [60]
MRS1042 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 pKi 60
pKi 5.5 [60]
flavone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.5 pKi 60
pKi 5.5 [60]
theophylline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 5.2 – 5.8 pKi 32,53,67,134
pKi 5.2 – 5.8 [32,53,67,134]
CVT-6883 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 pKi 36
pKi 5.5 (Ki 3.28x10-6 M) [36]
MRS1523 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.4 pKi 79
pKi 5.4 (Ki 3.66x10-6 M) [79]
PSB-10 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.2 pKi 96
pKi 5.2 (Ki 6.04x10-6 M) [96]
MRS928 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.2 pKi 60
pKi 5.2 [60]
tonapofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.2 pKi 61
pKi 5.2 (Ki 6.41x10-6 M) [61]
caffeine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.6 – 5.6 pKi 1,53,68
pKi 4.6 – 5.6 [1,53,68]
ATL802 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 5.1 pKi 65
pKi 5.1 (Ki 8.393x10-6 M) [65]
MRS1191 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 79
pKi <5.0 (Ki >1x10-5 M) [79]
MRS1191 Small molecule or natural product Click here for species-specific activity table Rn Antagonist <5.0 pKi 79
pKi <5.0 (Ki >1x10-5 M) [79]
VUF5574 Small molecule or natural product Click here for species-specific activity table Rn Antagonist >5.0 pKi 132
pKi >5.0 (Ki <1x10-5 M) [132]
PSB603 Small molecule or natural product Click here for species-specific activity table Hs Antagonist