A<sub>2A</sub> receptor | Adenosine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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A2A receptor

target has curated data in GtoImmuPdb

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

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 39,70,106
Mouse 7 410 10 Adora2a adenosine A2a receptor 83
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
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:  78
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:  72
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:  71
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
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:  45
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 Value Parameter Reference
[3H]CGS 21680 Hs Full agonist 7.7 – 7.8 pKd 54,140
pKd 7.7 – 7.8 (Kd 2.2x10-8 – 1.6x10-8 M) [54,140]
[3H]NECA Hs Full agonist 7.7 pKd 64
pKd 7.7 [64]
apadenoson Hs Agonist 9.3 pKi 105
pKi 9.3 (Ki 5x10-10 M) [105]
(R,S)-PHPNECA Hs Full agonist 8.5 pKi 139
pKi 8.5 [139]
2-hexynyl-NECA Hs Full agonist 8.2 – 8.3 pKi 28,66,139
pKi 8.2 – 8.3 [28,66,139]
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 80
pKi 8.0 (Ki 9.7x10-9 M) [80]
UK-432,097 Hs Agonist 7.7 – 8.3 pKi 48,145
pKi 7.7 – 8.3 [48,145]
NECA Hs Full agonist 6.9 – 8.7 pKi 10,28,43,61,66,146
pKi 6.9 – 8.7 [10,28,43,61,66,146]
CGS 21680 Rn Agonist 7.7 pKi 77
pKi 7.7 (Ki 1.9x10-8 M) [77]
CGS 21680 Hs Full agonist 6.7 – 8.1 pKi 10,28,43,53,61,64,66,99
pKi 6.7 – 8.1 (Ki 1.99x10-7 – 7.94x10-9 M) [10,28,43,53,61,64,66,99]
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 28,66
pKi 7.1 [28,66]
adenosine Rn Agonist 6.8 pKi 146
pKi 6.8 (Ki 1.5x10-7 M) [146]
2-chloroadenosine Hs Full agonist 6.7 – 6.8 pKi 61,66
pKi 6.7 – 6.8 [61,66]
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 53
pKi 6.6 (Ki 2.7x10-7 M) [53]
regadenoson Hs Agonist 6.5 pKi 53
pKi 6.5 (Ki 2.9x10-7 M) [53]
adenosine Hs Agonist 6.5 pKi 35-36,146
pKi 6.5 (Ki 3.1x10-7 M) [35-36,146]
CGS 24012 Hs Full agonist 6.4 pKi 61
pKi 6.4 [61]
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 77
pKi 6.3 (Ki 4.7x10-7 M) [77]
PENECA Hs Full agonist 6.2 pKi 139
pKi 6.2 [139]
cyclopentyladenosine Hs Full agonist 6.1 pKi 43,53,64
pKi 6.1 [43,53,64]
(R)-PIA Hs Full agonist 6.0 – 6.2 pKi 28,43,61,64,66
pKi 6.0 – 6.2 [28,43,61,64,66]
CCPA Rn Agonist 6.0 pKi 77
pKi 6.0 (Ki 9.5x10-7 M) [77]
cyclopentyladenosine Rn Agonist 6.0 pKi 77
pKi 6.0 (Ki 9.5x10-7 M) [77]
MRS3558 Rn Agonist 6.0 pKi 77
pKi 6.0 (Ki 1.08x10-6 M) [77]
piclidenoson Hs Full agonist 5.6 – 6.3 pKi 53,61,64
pKi 5.6 – 6.3 [53,61,64]
HEMADO Hs Agonist 5.9 pKi 65,139
pKi 5.9 (Ki 1.2x10-6 M) [65,139]
N(6)-cyclohexyladenosine Hs Full agonist 5.9 pKi 28,66
pKi 5.9 [28,66]
GR79236 Hs Agonist 5.9 pKi 53
pKi 5.9 (Ki 1.3x10-6 M) [53]
CV-1674 Hs Full agonist 5.8 pKi 66
pKi 5.8 [66]
tecadenoson Pig Agonist 5.6 pKi 53,91
pKi 5.6 (Ki 2.315x10-6 M) [53,91]
MRS3558 Hs Agonist 5.6 pKi 53
pKi 5.6 (Ki 2.33x10-6 M) [53]
CCPA Hs Full agonist 5.6 pKi 53,64
pKi 5.6 [53,64]
metrifudil Hs Full agonist 5.5 pKi 66
pKi 5.5 [66]
AB-MECA Hs Full agonist 5.4 pKi 64
pKi 5.4 [64]
APNEA Hs Full agonist 5.3 pKi 66
pKi 5.3 [66]
Cl-IB-MECA Hs Agonist 5.3 pKi 53
pKi 5.3 (Ki 5.36x10-6 M) [53]
(S)-PIA Hs Full agonist 5.0 – 5.1 pKi 28,64
pKi 5.0 – 5.1 [28,64]
Cl-IB-MECA Mm Agonist ~5.0 pKi 77
pKi ~5.0 (Ki ~1x10-5 M) [77]
BAY 60-6583 Hs Agonist <5.0 pKi 68
pKi <5.0 (Ki >1x10-5 M) [68]
GS9667 Hs Agonist <5.0 pKi 33
pKi <5.0 (Ki >1x10-5 M) [33]
MRS5151 Hs Agonist <5.0 pKi 86
pKi <5.0 (Ki >1x10-5 M) [86]
MRS5151 Mm Agonist <5.0 pKi 86
pKi <5.0 (Ki >1x10-5 M) [86]
MRS3558 Mm Agonist 5.0 pKi 77
pKi 5.0 (Ki 1.04x10-5 M) [77]
adenosine Hs Agonist - - 146
[146]
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 Rn Antagonist 9.2 pKd 104
pKd 9.2 [104]
[3H]ZM 241385 Hs Antagonist 8.7 – 9.1 pKd 4,42
pKd 8.7 – 9.1 (Kd 1.8x10-9 – 8x10-10 M) [4,42]
[3H]SCH 58261 Hs Antagonist 8.6 – 9.0 pKd 66,102
pKd 8.6 – 9.0 [66,102]
[3H]XAC Hs Antagonist 8.0 pKd 61
pKd 8.0 [61]
SCH442416 Hs Antagonist 8.4 – 10.3 pKi 126,129
pKi 8.4 – 10.3 [126,129]
MRS1093 Hs Antagonist 9.2 pKi 58
pKi 9.2 [58]
preladenant Hs Antagonist 9.1 pKi 90
pKi 9.1 (Ki 9x10-10 M) [90]
ZM-241385 Hs Antagonist 8.8 – 9.1 pKi 102
pKi 8.8 – 9.1 [102]
vipadenant Hs Antagonist 8.9 pKi 46
pKi 8.9 (Ki 1.3x10-9 M) [46]
SCH 58261 Hs Antagonist 8.3 – 9.2 pKi 28,66,102
pKi 8.3 – 9.2 [28,66,102]
xanthine amine congener Hs Antagonist 8.4 – 9.0 pKi 28,64
pKi 8.4 – 9.0 [28,64]
CGS 15943 Hs Antagonist 7.7 – 9.4 pKi 28,61,64,102
pKi 7.7 – 9.4 [28,61,64,102]
istradefylline Rn Antagonist 8.4 – 8.7 pKi 111,125
pKi 8.4 – 8.7 (Ki 4.46x10-9 – 2.2x10-9 M) [111,125]
tozadenant Hs Antagonist 8.3 pKi 25
pKi 8.3 (Ki 5x10-9 M) [25]
ST-1535 Hs Antagonist 8.2 pKi 87
pKi 8.2 (Ki 6.6x10-9 M) [87]
MSX-2 Rn Antagonist 8.1 pKi 92,119
pKi 8.1 (Ki 8.04x10-9 M) [92,119]
MSX-2 Hs Antagonist 7.8 – 8.3 pKi 119
pKi 7.8 – 8.3 (Ki 1.45x10-8 – 5.38x10-9 M) [119]
PBF-509 Hs Antagonist 7.6 – 7.9 pKi 47,85
pKi 7.9 (Ki 1.2x10-8 M) [47,85]
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) [47,85]
Description: Antagonism of rolipram-induced cAMP accummulation in CHO cells expressing the human A2A receptor, as measured using a proprietary enzymeimmunoassay.
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 52
pKi 7.3 (Ki 5.4x10-8 M) [52]
mefloquine Hs Antagonist 7.0 pKi 142
pKi 7.0 (Ki 1.04x10-7 M) [142]
Description: Binding affinity determined by displacement of [3H]-CGS21680 from human A2A receptors by increasing concentrations of racemic mefloquine.
DPCPX Hs Antagonist 6.6 – 7.2 pKi 28,64,66,102,143
pKi 6.6 – 7.2 [28,64,66,102,143]
MRE 3008F20 Hs Antagonist 6.8 pKi 53,132-133
pKi 6.8 [53,132-133]
LUF5981 Hs Antagonist 6.7 pKi 12
pKi 6.7 (Ki 1.94x10-7 M) [12]
rolofylline Hs Antagonist 6.2 – 7.0 pKi 59,107
pKi 6.2 – 7.0 (Ki 6.37x10-7 – 1.08x10-7 M) [59,107]
DPCPX Rn Antagonist 6.3 – 6.8 pKi 62,92
pKi 6.3 – 6.8 (Ki 5x10-7 – 1.57x10-7 M) [62,92]
derenofylline Hs Antagonist 6.4 pKi 57
pKi 6.4 (Ki 3.98x10-7 M) [57]
rolofylline Rn Antagonist 6.3 – 6.4 pKi 60,108
pKi 6.3 – 6.4 (Ki 5.1x10-7 – 3.8x10-7 M) [60,108]
KF26777 Hs Antagonist 6.3 pKi 114
pKi 6.3 (Ki 4.7x10-7 M) [114]
MRS1754 Hs Antagonist 6.3 pKi 63
pKi 6.3 (Ki 5.03x10-7 M) [63]
PSB36 Rn Antagonist 6.3 pKi 143
pKi 6.3 (Ki 5.52x10-7 M) [143]
MRS1754 Rn Antagonist 6.2 pKi 63
pKi 6.2 (Ki 6.12x10-7 M) [63]
CPX Hs Antagonist 6.2 pKi 61
pKi 6.2 [61]
ATL802 Hs Antagonist 6.2 pKi 63
pKi 6.2 (Ki 6.54x10-7 M) [63]
CPFPX Rn Antagonist 6.1 pKi 49
pKi 6.1 (Ki 8.12x10-7 M) [49]
CPFPX Hs Antagonist 6.0 pKi 49
pKi 6.0 (Ki 9.4x10-7 M) [49]
PSB36 Hs Antagonist 6.0 pKi 143
pKi 6.0 (Ki 9.8x10-7 M) [143]
MRE 2029F20 Hs Antagonist <6.0 pKi 6
pKi <6.0 (Ki >1x10-6 M) [6]
galangin Hs Antagonist 6.0 pKi 58
pKi 6.0 [58]
LAS38096 Hs Antagonist <6.0 pKi 30,137
pKi <6.0 (Ki >1x10-6 M) [30,137]
LUF7602 Hs Antagonist 5.9 pKi 147
pKi 5.9 (Ki 1.259x10-6 M) [147]
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 Hs Antagonist 5.9 pKi 53
pKi 5.9 (Ki 1.3x10-6 M) [53]
PSB-11 Hs Antagonist 5.9 pKi 103
pKi 5.9 (Ki 1.28x10-6 M) [103]
MRS1523 Rn Antagonist 5.7 pKi 77
pKi 5.7 (Ki 2.05x10-6 M) [77]
PSB-11 Rn Antagonist 5.7 pKi 103
pKi 5.7 (Ki 2.1x10-6 M) [103]
tonapofylline Rn Antagonist 5.6 pKi 59
pKi 5.6 (Ki 2.44x10-6 M) [59]
PSB-10 Hs Antagonist 5.6 pKi 103
pKi 5.6 (Ki 2.7x10-6 M) [103]
MRS1041 Hs Antagonist 5.5 pKi 58
pKi 5.5 [58]
MRS1042 Hs Antagonist 5.5 pKi 58
pKi 5.5 [58]
flavone Hs Antagonist 5.5 pKi 58
pKi 5.5 [58]
theophylline Hs Antagonist 5.2 – 5.8 pKi 28,51,64,132
pKi 5.2 – 5.8 [28,51,64,132]
CVT-6883 Hs Antagonist 5.5 pKi 32
pKi 5.5 (Ki 3.28x10-6 M) [32]
MRS1523 Hs Antagonist 5.4 pKi 77
pKi 5.4 (Ki 3.66x10-6 M) [77]
PSB-10 Rn Antagonist 5.2 pKi 94
pKi 5.2 (Ki 6.04x10-6 M) [94]
MRS928 Hs Antagonist 5.2 pKi 58
pKi 5.2 [58]
tonapofylline Hs Antagonist 5.2 pKi 59
pKi 5.2 (Ki 6.41x10-6 M) [59]
caffeine Hs Antagonist 4.6 – 5.6 pKi 1,51,66
pKi 4.6 – 5.6 [1,51,66]
ATL802 Mm Antagonist 5.1 pKi 63
pKi 5.1 (Ki 8.393x10-6 M) [63]
MRS1191 Hs Antagonist <5.0 pKi 77
pKi <5.0 (Ki >1x10-5 M) [77]
MRS1191 Rn Antagonist <5.0 pKi 77
pKi <5.0 (Ki >1x10-5 M) [77]
VUF5574 Rn Antagonist >5.0 pKi 130
pKi >5.0 (Ki <1x10-5 M) [130]
PSB603 Hs Antagonist <5.0 pKi 9
pKi <5.0 (Ki >1x10-5 M) [9]
PSB603 Rn Antagonist <5.0