A<sub>1</sub> receptor | Adenosine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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A1 receptor

target has curated data in GtoImmuPdb

Target id: 18

Nomenclature: A1 receptor

Family: Adenosine receptors

Gene and Protein Information
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
RDC7 | adenosine receptor A1 | A1-AR | A1R
Database Links
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
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
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]CCPA Hs Full agonist 9.2 pKd 78,120
pKd 9.2 (Kd 6.31x10-10 M) [78,120]
5-Cl-5-deoxy-(±)-ENBA Hs Full agonist 9.3 pKi 36
pKi 9.3 (Ki 5.1x10-10 M) [36]
N(6)-cyclohexyladenosine Rn Agonist 9.1 pKi 24
pKi 9.1 (Ki 8.5x10-10 M) [24]
(R)-PIA Rn Agonist 8.9 pKi 24
pKi 8.9 (Ki 1.2x10-9 M) [24]
CCPA Rn Agonist 8.9 pKi 85
pKi 8.9 (Ki 1.3x10-9 M) [85]
(R,S)-PHPNECA Hs Full agonist 8.6 pKi 148
pKi 8.6 [148]
TCPA Hs Agonist 8.6 pKi 9
pKi 8.6 (Ki 2.8x10-9 M) [9]
GR79236 Rn Agonist 8.5 pKi 63
pKi 8.5 (Ki 3.1x10-9 M) [63]
NECA Rn Agonist 8.3 pKi 90
pKi 8.3 (Ki 5.1x10-9 M) [90]
tecadenoson Pig Agonist 8.2 pKi 63,105
pKi 8.2 (Ki 6.5x10-9 M) [63,105]
2-chloroadenosine Rn Agonist 8.2 pKi 24
pKi 8.2 (Ki 6.7x10-9 M) [24]
compound 10 [PMID: 31306001] 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 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 Hs Full agonist 7.7 – 8.1 pKi 63,110
pKi 7.7 – 8.1 [63,110]
MRS3558 Mm Agonist 7.8 pKi 85
pKi 7.8 (Ki 1.58x10-8 M) [85]
LUF5831 Hs Partial agonist 7.7 pKi 54
pKi 7.7 [54]
(R)-PIA 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 Mm Agonist 7.5 pKi 85
pKi 7.5 (Ki 3.5x10-8 M) [85]
piclidenoson Hs Agonist 7.3 pKi 63
pKi 7.3 (Ki 5.1x10-8 M) [63]
GS9667 Hs Agonist 7.3 pKi 34
pKi 7.3 (Ki 5.5x10-8 M) [34]
2-hexynyl-NECA Hs Full agonist 7.2 pKi 148
pKi 7.2 [148]
adenosine Rn Agonist 7.1 pKi 155
pKi 7.1 (Ki 7.3x10-8 M) [155]
apadenoson Hs Agonist 7.1 pKi 63
pKi 7.1 (Ki 7.7x10-8 M) [63]
adenosine Hs Agonist ~7.0 pKi 155
pKi ~7.0 (Ki ~1x10-7 M) [155]
MRS3558 Rn Agonist 7.0 pKi 85
pKi 7.0 (Ki 1.05x10-7 M) [85]
NECA 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 Hs Agonist 6.7 pKi 63
pKi 6.7 (Ki 2.2x10-7 M) [63]
MRS3558 Hs Agonist 6.6 pKi 63
pKi 6.6 (Ki 2.6x10-7 M) [63]
Cl-IB-MECA Rn Agonist 6.6 pKi 85
pKi 6.6 (Ki 2.8x10-7 M) [85]
HEMADO Hs Agonist 6.5 pKi 77,148
pKi 6.5 (Ki 3.3x10-7 M) [77,148]
PENECA Hs Full agonist 6.2 pKi 148
pKi 6.2 [148]
CGS 21680 Hs Full agonist 5.8 – 6.4 pKi 41,63
pKi 5.8 – 6.4 [41,63]
CGS 21680 Rn Agonist 5.7 pKi 85
pKi 5.7 (Ki 1.8x10-6 M) [85]
2-chloroadenosine Hs Full agonist 5.2 – 5.6 pKi 64,120
pKi 5.2 – 5.6 [64,120]
(S)-PIA Hs Full agonist 4.6 – 6.0 pKi 64,140
pKi 4.6 – 6.0 [64,140]
CP608,039 Hs Agonist 5.1 pKi 63
pKi 5.1 (Ki 7.3x10-6 M) [63]
BAY 60-6583 Hs Agonist <5.0 pKi 81
pKi <5.0 (Ki >1x10-5 M) [81]
regadenoson Hs Agonist <5.0 pKi 63
pKi <5.0 (Ki >1x10-5 M) [63]
MRS5151 Mm Agonist 5.0 pKi 99
pKi 5.0 (Ki 1.05x10-5 M) [99]
MRS5151 Hs Agonist 4.8 pKi 99
pKi 4.8 (Ki 1.49x10-5 M) [99]
binodenoson Hs Agonist 4.3 pKi 63
pKi 4.3 (Ki 4.8x10-5 M) [63]
capadenoson Hs Partial agonist 10.0 pEC50 2
pEC50 10.0 (EC50 1x10-10 M) [2]
neladenoson Hs Partial agonist 10.0 pEC50 98
pEC50 10.0 (EC50 1x10-10 M) [98]
MRS7469 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 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 Hs Antagonist 7.5 pKd 36
pKd 7.5 [36]
PSB36 Rn Antagonist 9.9 pKi 1
pKi 9.9 (Ki 1.24x10-10 M) [1]
DPCPX 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 Rn Antagonist 9.2 pKi 57
pKi 9.2 (Ki 6.3x10-10 M) [57]
LUF5981 Hs Antagonist 9.1 pKi 17
pKi 9.1 (Ki 9x10-10 M) [17]
derenofylline Hs Antagonist 9.0 pKi 68
pKi 9.0 (Ki 1x10-9 M) [68]
FR194921 Hs Antagonist 8.9 pKi 93
pKi 8.9 [93]
CPFPX Hs Antagonist 8.9 pKi 57
pKi 8.9 (Ki 1.26x10-9 M) [57]
tonapofylline Rn Antagonist 8.9 pKi 73
pKi 8.9 (Ki 1.3x10-9 M) [73]
rolofylline Rn Antagonist 7.9 – 9.7 pKi 115
pKi 7.9 – 9.7 (Ki 1.26x10-8 – 1.9x10-10 M) [115]
WRC-0571 Hs Antagonist 8.8 pKi 96
pKi 8.8 [96]
rolofylline Hs Antagonist 8.1 – 9.1 pKi 73,115
pKi 8.1 – 9.1 (Ki 8x10-9 – 7.2x10-10 M) [73,115]
derenofylline Rn Antagonist 8.6 pKi 68
pKi 8.6 (Ki 2.51x10-9 M) [68]
CGS 15943 Hs Antagonist 8.5 pKi 112
pKi 8.5 (Ki 3.5x10-9 M) [112]
DPCPX 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 Rn Antagonist 8.2 pKi 89
pKi 8.2 (Ki 6.4x10-9 M) [89]
tonapofylline Hs Antagonist 8.1 pKi 73
pKi 8.1 (Ki 7.4x10-9 M) [73]
MRS1754 Rn Antagonist 7.8 pKi 75
pKi 7.8 (Ki 1.68x10-8 M) [75]
8-cyclopentyltheophylline Hs Antagonist 7.5 – 8.0 pKi 22
pKi 7.5 – 8.0 [22]
FK-453 Hs Antagonist 7.7 pKi 63
pKi 7.7 (Ki 1.8x10-8 M) [63]
xanthine amine congener Hs Antagonist 7.6 pKi 64
pKi 7.6 [64]
DU172 Hs Antagonist 7.4 pKi 49
pKi 7.4 [49]
vipadenant Hs Antagonist 7.2 pKi 46
pKi 7.2 (Ki 6.8x10-8 M) [46]
ST-1535 Hs Antagonist 7.1 pKi 102
pKi 7.1 (Ki 7.18x10-8 M) [102]
AZD4635 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 Hs Antagonist 6.7 pKi 7,144
pKi 6.7 [7,144]
istradefylline Rn Antagonist 6.6 pKi 39
pKi 6.6 (Ki 2.3x10-7 M) [39]
AS70 Hs Antagonist 6.6 pKi 144
pKi 6.6 [144]
AS100 Hs Antagonist 6.5 pKi 144
pKi 6.5 [144]
ATL802 Hs Antagonist 6.4 pKi 75
pKi 6.4 (Ki 3.69x10-7 M) [75]
MRS1754 Hs Antagonist 6.4 pKi 75
pKi 6.4 (Ki 4.03x10-7 M) [75]
PSB-11 Rn Antagonist 6.4 pKi 113
pKi 6.4 (Ki 4.4x10-7 M) [113]
ZM-241385 Hs Antagonist 6.1 – 6.6 pKi 63,112
pKi 6.1 – 6.6 [63,112]
MRS928 Rn Antagonist 6.3 pKi 72
pKi 6.3 [72]
L-97-1 Hs Antagonist 6.2 pKi 110
pKi 6.2 [110]
MRS1041 Rn Antagonist 6.2 pKi 72
pKi 6.2 [72]
SCH 58261 Hs Antagonist 6.1 – 6.3 pKi 63,112,140
pKi 6.1 – 6.3 [63,112,140]
mefloquine 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 Hs Antagonist 6.1 pKi 144
pKi 6.1 [144]
galangin Rn Antagonist 6.1 pKi 72
pKi 6.1 [72]
LUF7602 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 Rn Antagonist 6.1 pKi 107
pKi 6.1 (Ki 8.05x10-7 M) [107]
istradefylline Hs Antagonist 6.1 pKi 39
pKi 6.1 (Ki 8.41x10-7 M) [39]
MSX-2 Rn Antagonist 6.1 pKi 125
pKi 6.1 (Ki 9x10-7 M) [125]
MRS1042 Rn Antagonist 6.0 pKi 72
pKi 6.0 [72]
preladenant Hs Antagonist <6.0 pKi 104
pKi <6.0 (Ki >1x10-6 M) [104]
MRE 3008F20 Hs Antagonist 5.9 – 6.0 pKi 63,144-145
pKi 5.9 – 6.0 [63,144-145]
SCH442416 Hs Antagonist 5.9 pKi 63
pKi 5.9 (Ki 1.11x10-6 M) [63]
PSB-11 Hs Antagonist 5.8 pKi 113
pKi 5.8 (Ki 1.64x10-6 M) [113]
PSB-10 Hs Antagonist 5.8 pKi 113
pKi 5.8 (Ki 1.7x10-6 M) [113]
KF26777 Hs Antagonist 5.7 pKi 121
pKi 5.7 (Ki 1.8x10-6 M) [121]
CVT-6883 Hs Antagonist 5.7 pKi 33
pKi 5.7 (Ki 1.94x10-6 M) [33]
MRS1093 Rn Antagonist 5.7 pKi 72
pKi 5.7 [72]
PSB1115 Rn Antagonist 5.7 pKi 106
pKi 5.7 (Ki 2.2x10-6 M) [106]
MRS1132 Rn Antagonist 5.6 pKi 72
pKi 5.6 [72]
MSX-2 Hs Antagonist 5.6 pKi 125
pKi 5.6 (Ki 2.5x10-6 M) [125]
LAS38096 Hs Antagonist 5.6 pKi 32,146
pKi 5.6 (Ki 2.821x10-6 M) [32,146]
flavone Rn Antagonist 5.5 pKi 72
pKi 5.5 [72]
isobutylmethylxanthine Hs Antagonist 5.1 pKi 64
pKi 5.1 [64]
sakuranetin Rn Antagonist 5.1 pKi 72
pKi 5.1 [72]
theophylline Hs Antagonist 4.9 – 5.2 pKi 35,64,78,144
pKi 4.9 – 5.2 [35,64,78,144]
ATL802 Mm Antagonist 5.0 pKi 75
pKi 5.0 (Ki 9.583x10-6 M) [75]
MRS1191 Hs Antagonist <5.0 pKi 85
pKi <5.0 (Ki >1x10-5 M) [85]
MRS1523 Hs Antagonist <5.0 pKi 85
pKi <5.0 (Ki >1x10-5 M) [85]
VUF5574 Rn Antagonist >5.0 pKi 143
pKi >5.0 (Ki <1x10-5 M) [143]
PSB603 Hs Antagonist <5.0 pKi 13
pKi <5.0 (Ki >1x10-5 M) [13]
PSB603 Rn Antagonist <5.0 pKi 13
pKi <5.0 (Ki >1x10-5 M) [13]
PSB1115 Hs Antagonist <5.0 pKi 53
pKi <5.0 (Ki >1x10-5 M) [53]
theophylline 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 Rn Antagonist 4.9 pKi 72
pKi 4.9 [72]
MRS1523 Rn Antagonist 4.8 pKi 85
pKi 4.8 (Ki 1.56x10-5 M) [