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A1 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 18

Nomenclature: A1 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 7 326 1q32.1 ADORA1 adenosine A1 receptor 86,117,141
Mouse 7 326 1 E4 Adora1 adenosine A1 receptor 95,152
Rat 7 326 13q13 Adora1 adenosine A1 receptor 94
Previous and Unofficial Names Click here for help
RDC7 | adenosine receptor A1 | A1-AR | A1R
Database Links Click here for help
Specialist databases
GPCRDB aa1r_human (Hs), aa1r_mouse (Mm), aa1r_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human adenosine A1 receptor A1AR-bRIL in complex with the covalent antagonist DU172 at 3.2A resolution
PDB Id:  5UEN
Ligand:  DU172
Resolution:  3.2Å
Species:  Human
References:  49
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of stabilized A1 receptor in complex with PSB36
PDB Id:  5N2S
Ligand:  PSB36
Resolution:  3.3Å
Species:  Human
References:  18
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the adenosine-bound human adenosine A1 receptor–Gi complex
PDB Id:  6D9H
Ligand:  adenosine
Resolution:  3.6Å
Species:  Human
References:  30
Natural/Endogenous Ligands Click here for help
adenosine

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]CCPA Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.2 pKd 78,120
pKd 9.2 (Kd 6.31x10-10 M) [78,120]
5-Cl-5-deoxy-(±)-ENBA Small molecule or natural product Hs Full agonist 9.3 pKi 36
pKi 9.3 (Ki 5.1x10-10 M) [36]
N(6)-cyclohexyladenosine Small molecule or natural product Click here for species-specific activity table Rn Agonist 9.1 pKi 24
pKi 9.1 (Ki 8.5x10-10 M) [24]
(R)-PIA Small molecule or natural product Click here for species-specific activity table Rn Agonist 8.9 pKi 24
pKi 8.9 (Ki 1.2x10-9 M) [24]
CCPA Small molecule or natural product Click here for species-specific activity table Rn Agonist 8.9 pKi 85
pKi 8.9 (Ki 1.3x10-9 M) [85]
(R,S)-PHPNECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.6 pKi 148
pKi 8.6 [148]
TCPA Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.6 pKi 9
pKi 8.6 (Ki 2.8x10-9 M) [9]
GR79236 Small molecule or natural product Rn Agonist 8.5 pKi 63
pKi 8.5 (Ki 3.1x10-9 M) [63]
NECA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 8.3 pKi 90
pKi 8.3 (Ki 5.1x10-9 M) [90]
tecadenoson Small molecule or natural product Primary target of this compound Click here for species-specific activity table Pig Agonist 8.2 pKi 63,105
pKi 8.2 (Ki 6.5x10-9 M) [63,105]
2-chloroadenosine Small molecule or natural product Click here for species-specific activity table Rn Agonist 8.2 pKi 24
pKi 8.2 (Ki 6.7x10-9 M) [24]
compound 10 [PMID: 31306001] Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist 8.1 pKi 8
pKi 8.1 (Ki 7.22x10-9 M) [8]
Description: Binding affinity calculated by measuring displacement of specific [3H]DPCPX binding at hA1ARs expressed in CHO cells.
cyclopentyladenosine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.5 – 9.4 pKi 22,25,41,54,63-64,120
pKi 6.5 – 9.4 [22,25,41,54,63-64,120]
CCPA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.7 – 8.1 pKi 63,110
pKi 7.7 – 8.1 [63,110]
MRS3558 Small molecule or natural product Click here for species-specific activity table Mm Agonist 7.8 pKi 85
pKi 7.8 (Ki 1.58x10-8 M) [85]
LUF5831 Small molecule or natural product Hs Partial agonist 7.7 pKi 54
pKi 7.7 [54]
(R)-PIA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.4 – 8.7 pKi 41,64,78,120,140
pKi 6.4 – 8.7 [41,64,78,120,140]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Mm Agonist 7.5 pKi 85
pKi 7.5 (Ki 3.5x10-8 M) [85]
piclidenoson Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 7.3 pKi 63
pKi 7.3 (Ki 5.1x10-8 M) [63]
GS9667 Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.3 pKi 34
pKi 7.3 (Ki 5.5x10-8 M) [34]
2-hexynyl-NECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.2 pKi 148
pKi 7.2 [148]
adenosine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Agonist 7.1 pKi 155
pKi 7.1 (Ki 7.3x10-8 M) [155]
apadenoson Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.1 pKi 63
pKi 7.1 (Ki 7.7x10-8 M) [63]
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 ~7.0 pKi 155
pKi ~7.0 (Ki ~1x10-7 M) [155]
MRS3558 Small molecule or natural product Click here for species-specific activity table Rn Agonist 7.0 pKi 85
pKi 7.0 (Ki 1.05x10-7 M) [85]
NECA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.3 – 8.2 pKi 41,64,120,140,155
pKi 5.3 – 8.2 [41,64,120,140,155]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pKi 63
pKi 6.7 (Ki 2.2x10-7 M) [63]
MRS3558 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 pKi 63
pKi 6.6 (Ki 2.6x10-7 M) [63]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.6 pKi 85
pKi 6.6 (Ki 2.8x10-7 M) [85]
HEMADO Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.5 pKi 77,148
pKi 6.5 (Ki 3.3x10-7 M) [77,148]
PENECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 pKi 148
pKi 6.2 [148]
CGS 21680 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.8 – 6.4 pKi 41,63
pKi 5.8 – 6.4 [41,63]
CGS 21680 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 5.7 pKi 85
pKi 5.7 (Ki 1.8x10-6 M) [85]
2-chloroadenosine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 – 5.6 pKi 64,120
pKi 5.2 – 5.6 [64,120]
(S)-PIA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.6 – 6.0 pKi 64,140
pKi 4.6 – 6.0 [64,140]
CP608,039 Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.1 pKi 63
pKi 5.1 (Ki 7.3x10-6 M) [63]
BAY 60-6583 Small molecule or natural product Click here for species-specific activity table Hs Agonist <5.0 pKi 81
pKi <5.0 (Ki >1x10-5 M) [81]
regadenoson Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist <5.0 pKi 63
pKi <5.0 (Ki >1x10-5 M) [63]
MRS5151 Small molecule or natural product Click here for species-specific activity table Mm Agonist 5.0 pKi 99
pKi 5.0 (Ki 1.05x10-5 M) [99]
MRS5151 Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.8 pKi 99
pKi 4.8 (Ki 1.49x10-5 M) [99]
binodenoson Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.3 pKi 63
pKi 4.3 (Ki 4.8x10-5 M) [63]
capadenoson Small molecule or natural product Hs Partial agonist 10.0 pEC50 2
pEC50 10.0 (EC50 1x10-10 M) [2]
neladenoson Small molecule or natural product Hs Partial agonist 10.0 pEC50 98
pEC50 10.0 (EC50 1x10-10 M) [98]
MRS7469 Small molecule or natural product Hs Agonist - - 139
[139]
View species-specific agonist tables
Agonist Comments
The role for adenosine as endogenous ligand for the A1 receptor is described in [37] and [38].

The role for adenosine as endogenous ligand for the A1 receptor is described in [38] and [39].

Capadenoson and neladenoson have been evaluated in phase 2 clinical trials for heart failure, but failed to meet expectations [149].

Primary target mapping: we have tagged the adenosine A1 receptor as the primary target for this endogenous ligand as the affinity is marginally higher at this receptor isoform. However, adenosine is likely to exert clinical effects via other adenosine receptor family members.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]DPCPX Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.4 – 9.2 pKd 22,35,78,112,120,140
pKd 8.4 – 9.2 (Kd 1.2x10-9 – 6x10-10 M) [22,35,78,112,120,140]
xanthine amine congener Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.5 pKd 36
pKd 7.5 [36]
PSB36 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 9.9 pKi 1
pKi 9.9 (Ki 1.24x10-10 M) [1]
DPCPX Small molecule or natural product Click here for species-specific activity table Rn Antagonist 9.0 – 9.7 pKi 74,79,151
pKi 9.0 – 9.7 (Ki 1x10-9 – 1.8x10-10 M) [74,79,151]
CPFPX Small molecule or natural product Click here for species-specific activity table Rn Antagonist 9.2 pKi 57
pKi 9.2 (Ki 6.3x10-10 M) [57]
LUF5981 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 pKi 17
pKi 9.1 (Ki 9x10-10 M) [17]
derenofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.0 pKi 68
pKi 9.0 (Ki 1x10-9 M) [68]
FR194921 Small molecule or natural product Hs Antagonist 8.9 pKi 93
pKi 8.9 [93]
CPFPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 pKi 57
pKi 8.9 (Ki 1.26x10-9 M) [57]
tonapofylline Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.9 pKi 73
pKi 8.9 (Ki 1.3x10-9 M) [73]
rolofylline Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.9 – 9.7 pKi 115
pKi 7.9 – 9.7 (Ki 1.26x10-8 – 1.9x10-10 M) [115]
WRC-0571 Small molecule or natural product Hs Antagonist 8.8 pKi 96
pKi 8.8 [96]
rolofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 – 9.1 pKi 73,115
pKi 8.1 – 9.1 (Ki 8x10-9 – 7.2x10-10 M) [73,115]
derenofylline Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.6 pKi 68
pKi 8.6 (Ki 2.51x10-9 M) [68]
CGS 15943 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 112
pKi 8.5 (Ki 3.5x10-9 M) [112]
DPCPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.4 – 9.2 pKi 25,60,110,120,151
pKi 7.4 – 9.2 (Ki 3.98x10-8 – 6.3x10-10 M) [25,60,110,120,151]
CGS 15943 Small molecule or natural product Rn Antagonist 8.2 pKi 89
pKi 8.2 (Ki 6.4x10-9 M) [89]
tonapofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 pKi 73
pKi 8.1 (Ki 7.4x10-9 M) [73]
MRS1754 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.8 pKi 75
pKi 7.8 (Ki 1.68x10-8 M) [75]
8-cyclopentyltheophylline Small molecule or natural product Hs Antagonist 7.5 – 8.0 pKi 22
pKi 7.5 – 8.0 [22]
FK-453 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 pKi 63
pKi 7.7 (Ki 1.8x10-8 M) [63]
xanthine amine congener Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.6 pKi 64
pKi 7.6 [64]
DU172 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 7.4 pKi 49
pKi 7.4 [49]
vipadenant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 7.2 pKi 46
pKi 7.2 (Ki 6.8x10-8 M) [46]
ST-1535 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 102
pKi 7.1 (Ki 7.18x10-8 M) [102]
AZD4635 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 6.8 pKi 12
pKi 6.8 (Ki 1.6x10-7 M) [12]
Description: Binding affinity of AZD4635 determined in a radioligand binding competition assays with membranes prepared from CHO cells stably expressing human A1R.
MRE 2029F20 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 pKi 7,144
pKi 6.7 [7,144]
istradefylline Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 6.6 pKi 39
pKi 6.6 (Ki 2.3x10-7 M) [39]
AS70 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 pKi 144
pKi 6.6 [144]
AS100 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.5 pKi 144
pKi 6.5 [144]
ATL802 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 75
pKi 6.4 (Ki 3.69x10-7 M) [75]
MRS1754 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 75
pKi 6.4 (Ki 4.03x10-7 M) [75]
PSB-11 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.4 pKi 113
pKi 6.4 (Ki 4.4x10-7 M) [113]
ZM-241385 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.1 – 6.6 pKi 63,112
pKi 6.1 – 6.6 [63,112]
MRS928 Small molecule or natural product Rn Antagonist 6.3 pKi 72
pKi 6.3 [72]
L-97-1 Small molecule or natural product Hs Antagonist 6.2 pKi 110
pKi 6.2 [110]
MRS1041 Small molecule or natural product Rn Antagonist 6.2 pKi 72
pKi 6.2 [72]
SCH 58261 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 – 6.3 pKi 63,112,140
pKi 6.1 – 6.3 [63,112,140]
mefloquine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.2 pKi 150
pKi 6.2 (Ki 6.75x10-7 M) [150]
Description: Binding affinity determined by displacement of [3H]-DPCPX from human A1 receptors by increasing concentrations of racemic mefloquine.
AS99 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 pKi 144
pKi 6.1 [144]
galangin Small molecule or natural product Rn Antagonist 6.1 pKi 72
pKi 6.1 [72]
LUF7602 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 pKi 157
pKi 6.1 (Ki 7.94x10-7 M) [157]
Description: Affinity determined from the displacement of specific [3H]DPCPX binding on CHO cell membranes stably expressing human adenosine A1 receptors at 25 °C during 2 h of incubation.
PSB-10 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.1 pKi 107
pKi 6.1 (Ki 8.05x10-7 M) [107]
istradefylline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.1 pKi 39
pKi 6.1 (Ki 8.41x10-7 M) [39]
MSX-2 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.1 pKi 125
pKi 6.1 (Ki 9x10-7 M) [125]
MRS1042 Small molecule or natural product Rn Antagonist 6.0 pKi 72
pKi 6.0 [72]
preladenant Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist <6.0 pKi 104
pKi <6.0 (Ki >1x10-6 M) [104]
MRE 3008F20 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 – 6.0 pKi 63,144-145
pKi 5.9 – 6.0 [63,144-145]
SCH442416 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 63
pKi 5.9 (Ki 1.11x10-6 M) [63]
PSB-11 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.8 pKi 113
pKi 5.8 (Ki 1.64x10-6 M) [113]
PSB-10 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.8 pKi 113
pKi 5.8 (Ki 1.7x10-6 M) [113]
KF26777 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.7 pKi 121
pKi 5.7 (Ki 1.8x10-6 M) [121]
CVT-6883 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.7 pKi 33
pKi 5.7 (Ki 1.94x10-6 M) [33]
MRS1093 Small molecule or natural product Rn Antagonist 5.7 pKi 72
pKi 5.7 [72]
PSB1115 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Rn Antagonist 5.7 pKi 106
pKi 5.7 (Ki 2.2x10-6 M) [106]
MRS1132 Small molecule or natural product Rn Antagonist 5.6 pKi 72
pKi 5.6 [72]
MSX-2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pKi 125
pKi 5.6 (Ki 2.5x10-6 M) [125]
LAS38096 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pKi 32,146
pKi 5.6 (Ki 2.821x10-6 M) [32,146]
flavone Small molecule or natural product Ligand has a PDB structure Rn Antagonist 5.5 pKi 72
pKi 5.5 [72]
isobutylmethylxanthine Small molecule or natural product Ligand has a PDB structure Hs Antagonist 5.1 pKi 64
pKi 5.1 [64]
sakuranetin Small molecule or natural product Ligand has a PDB structure Rn Antagonist 5.1 pKi 72
pKi 5.1 [72]
theophylline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 4.9 – 5.2 pKi 35,64,78,144
pKi 4.9 – 5.2 [35,64,78,144]
ATL802 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 5.0 pKi 75
pKi 5.0 (Ki 9.583x10-6 M) [75]
MRS1191 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 85
pKi <5.0 (Ki >1x10-5 M) [85]
MRS1523 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 85
pKi <5.0 (Ki >1x10-5 M) [85]
VUF5574 Small molecule or natural product Click here for species-specific activity table Rn Antagonist >5.0 pKi 143
pKi >5.0 (Ki <1x10-5 M) [143]
PSB603 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 13
pKi <5.0 (Ki >1x10-5 M) [13]
PSB603 Small molecule or natural product Click here for species-specific activity table Rn Antagonist <5.0 pKi 13
pKi <5.0 (Ki >1x10-5 M) [13]
PSB1115 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist <5.0 pKi 53
pKi <5.0 (Ki >1x10-5 M) [53]
theophylline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Rn Antagonist 4.8 – 5.1 pKi 61,106
pKi 4.8 – 5.1 (Ki 1.4x10-5 – 8.74x10-6 M) [61,106]
morin Small molecule or natural product Ligand has a PDB structure Rn Antagonist 4.9 pKi 72
pKi 4.9 [72]
MRS1523 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.8 pKi 85
pKi 4.8 (Ki 1.56x10-5 M) [85]
caffeine Small molecule or natural product