ADORA2A

Summary

ADORA2A (adenosine A2a receptor, HGNC:263) is a protein-coding gene on chromosome 22q11.23, encoding Adenosine receptor A2a (P29274). Receptor for adenosine.

This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily, which is subdivided into classes and subtypes. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein, an adenosine receptor of A2A subtype, uses adenosine as the preferred endogenous agonist and preferentially interacts with the G(s) and G(olf) family of G proteins to increase intracellular cAMP levels. It plays an important role in many biological functions, such as cardiac rhythm and circulation, cerebral and renal blood flow, immune function, pain regulation, and sleep. It has been implicated in pathophysiological conditions such as inflammatory diseases and neurodegenerative disorders. Alternative splicing results in multiple transcript variants. A read-through transcript composed of the upstream SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding.

Source: NCBI Gene 135 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 123 total — 21 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes — 81 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:263
Approved symbol	ADORA2A
Name	adenosine A2a receptor
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	RDC8
Ensembl gene	ENSG00000128271
Ensembl biotype	protein_coding
OMIM	102776
Entrez	135

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 42 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000337539, ENST00000424232, ENST00000436735, ENST00000439591, ENST00000444262, ENST00000464977, ENST00000467385, ENST00000472248, ENST00000486108, ENST00000486351, ENST00000496258, ENST00000496497, ENST00000610595, ENST00000611543, ENST00000618076, ENST00000880349, ENST00000880350, ENST00000880351, ENST00000880352, ENST00000880353, ENST00000880354, ENST00000880355, ENST00000880356, ENST00000880357, ENST00000880358, ENST00000880359, ENST00000880360, ENST00000880361, ENST00000880362, ENST00000880363, ENST00000925457, ENST00000925458, ENST00000925459, ENST00000925460, ENST00000940965, ENST00000940966, ENST00000940967, ENST00000940968, ENST00000940969, ENST00000940970, ENST00000940971, ENST00000940972, ENST00000940973, ENST00000940974, ENST00000940975

RefSeq mRNA: 5 — MANE Select: NM_000675 NM_000675, NM_001278497, NM_001278498, NM_001278499, NM_001278500

CCDS: CCDS13826

Canonical transcript exons

ENST00000337539 — 3 exons

Exon	Start	End
ENSE00002241361	24440583	24442357
ENSE00002322583	24427599	24427746
ENSE00003792508	24433131	24433736

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 96.56.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8808 / max 909.5397, expressed in 762 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191384	2.2262	640
191388	1.2922	157
191383	1.2125	306
191389	0.9423	133
191387	0.4369	113
191390	0.1936	46
191394	0.1729	31
191385	0.0887	26
191393	0.0850	25
191395	0.0714	20

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	96.56	gold quality
caudate nucleus	UBERON:0001873	94.77	gold quality
nucleus accumbens	UBERON:0001882	94.04	gold quality
blood	UBERON:0000178	92.12	gold quality
bone marrow	UBERON:0002371	88.85	gold quality
right lobe of liver	UBERON:0001114	88.16	gold quality
lymph node	UBERON:0000029	87.49	gold quality
apex of heart	UBERON:0002098	87.28	gold quality
granulocyte	CL:0000094	85.90	gold quality
bone marrow cell	CL:0002092	85.54	gold quality
metanephros cortex	UBERON:0010533	84.73	gold quality
vermiform appendix	UBERON:0001154	84.68	gold quality
liver	UBERON:0002107	83.33	gold quality
spleen	UBERON:0002106	82.27	gold quality
heart left ventricle	UBERON:0002084	80.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.20	gold quality
brain	UBERON:0000955	79.97	gold quality
upper lobe of left lung	UBERON:0008952	79.84	gold quality
leukocyte	CL:0000738	79.65	gold quality
cerebellum	UBERON:0002037	79.54	gold quality
cerebellar hemisphere	UBERON:0002245	79.47	gold quality
cerebellar cortex	UBERON:0002129	79.42	gold quality
ganglionic eminence	UBERON:0004023	79.03	gold quality
monocyte	CL:0000576	79.01	gold quality
cortex of kidney	UBERON:0001225	78.88	gold quality
adult mammalian kidney	UBERON:0000082	78.46	gold quality
heart	UBERON:0000948	78.06	gold quality
lung	UBERON:0002048	78.05	gold quality
right frontal lobe	UBERON:0002810	77.60	gold quality
right atrium auricular region	UBERON:0006631	77.34	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	25.64
E-MTAB-7381	no	391.43
E-ANND-3	no	2.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CREBBP, CXXC1, EPAS1, NFIA, NFKB1, RELA, YY1, ZNF148

miRNA regulators (miRDB)

69 targeting ADORA2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6832-3P	99.52	70.44	1726

Literature-anchored findings (GeneRIF, showing 40)

• A(1)- and A(2a)-adenosine receptor activation protects HK-2 proximal kidney tubule cells against H(2)O(2)-induced injury (PMID:11934694)
• Removal of the entire carboxy terminus of human A2aRT blunts the ability of the receptor to constitutively elevate cyclic AMP in intact cells; in contrast, MAP kinase stimulation is not affected by the truncation. (PMID:12237741)
• adenosine triggers a survival signal via A3 receptor activation and it kills the cell through A2A receptor inducing a signaling pathway that involves protein kinase C and mitogen-activated protein kinases. (PMID:12406340)
• The A2A receptor mediates a negative feedback pathway to modulate cytokine expression in THP-1 cells (PMID:12429726)
• No evidence for genetically determined reduction of adenosine A 2(A) receptors in schizophrenia. Role of adenosine A (2A) receptors in the molecular effects of antipsychotic drugs. (PMID:12634474)
• The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells. (PMID:12784121)
• adenosine A2A Receptor, either homomeric or heteromeric with dopamine D2 receptors, exists as an oligomer in living cells (PMID:12804599)
• an alpha-actinin-dependent association between the actin cytoskeleton and A2AR trafficking (PMID:12837758)
• Molecular modeling of the human A2a adenosine receptor. (PMID:12856413)
• In the most probable of two possible modes of interaction between D2R and A2AR, helix 5 and/or helix 6 and the N-terminal portion of I3 from D2R approached helix 4 and the C-terminal portion of the C-tail from the A2AR, respectively (PMID:12933819)
• Adenosine binding to A(2A)AR counteracts stimulation of neutrophil CD49d integrin expression (PMID:14525968)
• Evidence is found for a susceptibility locus for panic disorder, possibly including agoraphobia, either within the ADORA2A gene or in a nearby region of chromosome 22. (PMID:14666117)
• Most damage after hepatic ischemia occurs during reperfusion and can be blocked by adenosine A2a receptor activation. (PMID:14715520)
• adenosine-related gene variants do not appear to alter susceptibility to the disease in this group of essential hypertensives (PMID:15257174)
• A2A receptor activation increases protein phosphatase activity, which blocks IP3 receptor-regulated calcium release and reduction of intracellular calcium inhibits TNF-alpha production in monocytes (PMID:15351206)
• The tendency of some peptides of adenosine A2a receptor to self-associate, especially in aqueous environments, underscores the need to prevent improper interactions during folding and refolding of membrane proteins in vivo and in vitro (PMID:15461468)
• Adenosine A2A and dopamine D3 receptors seem to form A2A/D3 heteromeric receptor complexes in which A2A receptors antagonistically modulate both the affinity and the signaling of the D3 receptors when they are colocalized in the plasma membrane. (PMID:15539641)
• PBMC from CHF patients how an upregulation of A2AR-mediated inhibition of TNF-alpha, which may represent a mechanism of protection against inappropriate cytokine production. (PMID:15704067)
• Our findings suggest that it is unlikely that the A2aAR 1976T > C polymorphism plays a major role in the pathogenesis of PD, schizophrenia, or antipsychotic-induced tardive dyskinesia in the Chinese population. (PMID:15719154)
• Modeled pairs of A(2A)AR-derived neoceptor-neoligand, which are pharmacologically orthogonal with respect to the native species. (PMID:15734651)
• The 1976C > T polymorphism of ADORA2A receptor may be in linkage disequilibrium with a functional variant that affects panic disorder, and the extent of this linkage disequilibrium is not similar for all ethnic populations. (PMID:15774265)
• Evidence of an individual adenosine A2A receptor transmembrane domain self-association. (PMID:15987888)
• Regulation of adenosine receptor expression, especially up-regulation of the A(2A)AR, is part of a delayed feedback mechanism initiated through NF-kappaB to terminate the activation of human and mouse macrophages. (PMID:16022683)
• An increased platelet A2A receptor maximum receptor binding may belong in a cascade of toxic events leading to earlier onset of Huntington’s disease. (PMID:16184606)
• Modulation by A2AR in the production of inflammatory signals by neutrophils may influence the evolution of an inflammatory response by reducing the activation status of inflammatory cells. (PMID:16280366)
• Activation of the A(2A) receptor might have a beneficial effect by inhibiting inflammatory cell influx and downregulating inflammatory cell activation in asthma and COPD, respectively. (PMID:16339780)
• Adenosine A2a receptor is involved in bronchial epithelial cell adenosine-stimulated wound healing. (PMID:16361356)
• Galpha(olf) variant XLGalpha(olf) interacts with the human adenosine A2A receptor (PMID:16818375)
• A2A upregulation in prefrontal cortex may contribute to memory dysfunction in depression (PMID:16824773)
• adenosine inhibits MMP-9 secretion by neutrophils; this effect involves the A2a receptor and is mediated through the cAMP/PKA/Ca(2+) pathway (PMID:16917093)
• The changes in peripheral A(2A) receptor expression suggest a significant inflammatory response to HD and heart or kidney failure. (PMID:17132707)
• a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep (PMID:17329997)
• The G(alphas)-coupled adenosine A2A receptor closes KCa3.1, providing a clearly defined mechanism by which adenosine inhibits human lung mast cell migration and degranulation. (PMID:17474152)
• A(2A) receptor B(max) values are robustly increased at all Huntingon disease stages as well as in 32 pre-symptomatic subjects (PMID:17512749)
• the 1976C>T polymorphism does not affect the vasodilator response to adenosine and caffeine in vivo (PMID:17558310)
• Results describe the isolation and spectroscopic characterization of functional human adenosine A2a receptor. (PMID:17591446)
• an increased number and an up-regulation of adenosine A2A receptors in patients with spontaneous syncope and a positive head-up tilt, which in the context of high APLs may play a role in the recurrence of syncopal episodes (PMID:17599669)
• Findings show that the probability of having the ADORA2A 1083TT genotype decreases as habitual caffeine consumption increases. This observation provides a biologic basis for caffeine consumption behavior (PMID:17616786)
• Adenosine A2A receptors signal for increased collagen production by multiple signaling pathways, promoting the hypothesis that adenosine receptors promote hepatic fibrosis. (PMID:17872970)
• A2A receptors open Cl- channels in pancreatic ducts cells with functional cystic fibrosis transmembrane regulator (CFTR). (PMID:18057956)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adora2aa	ENSDARG00000033706
mus_musculus	Adora2a	ENSMUSG00000020178
rattus_norvegicus	Adora2a	ENSRNOG00000001302
drosophila_melanogaster	AdoR	FBGN0039747

Paralogs (3): ADORA1 (ENSG00000163485), ADORA2B (ENSG00000170425), ADORA3 (ENSG00000282608)

Protein

Protein identifiers

Adenosine receptor A2a — P29274 (reviewed: P29274)

All UniProt accessions (9): P29274, C9J0Z4, C9J3T2, C9JFS2, C9JQD8, S4R2Z8, S4R3A7, S4R429, X5DNB4

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.

Subunit / interactions. Interacts (via cytoplasmic C-terminal domain) with USP4; the interaction is direct. May interact with DRD4. Interacts with NECAB2. Interacts (via cytoplasmic C-terminal domain) with GAS2L2; interaction enhances receptor-mediated adenylyl cyclase activity.

Subcellular location. Cell membrane.

Post-translational modifications. Ubiquitinated. Deubiquitinated by USP4; leading to stabilization and expression at the cell surface.

Domain organisation. The cytoplasmic C-terminal domain is necessary for targeting the non-ubiquitinated form of this protein to the cell surface.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (5): NP_000666, NP_001265426, NP_001265427, NP_001265428, NP_001265429 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001513	Adeno_A2A_rcpt	Family
IPR001634	Adenosn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (54 total): helix 17, topological domain 8, transmembrane region 7, strand 6, binding site 4, disulfide bond 4, sequence variant 3, turn 2, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

188 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5NM4	X-RAY DIFFRACTION	1.7
9H37	X-RAY DIFFRACTION	1.72
5IU4	X-RAY DIFFRACTION	1.72
9H2X	X-RAY DIFFRACTION	1.75
4EIY	X-RAY DIFFRACTION	1.8
6LPJ	X-RAY DIFFRACTION	1.8
6LPK	X-RAY DIFFRACTION	1.8
7IO5	X-RAY DIFFRACTION	1.84
7IPE	X-RAY DIFFRACTION	1.84
6PS7	X-RAY DIFFRACTION	1.85
5OLG	X-RAY DIFFRACTION	1.87
7IPC	X-RAY DIFFRACTION	1.87
7IOZ	X-RAY DIFFRACTION	1.88
7IOR	X-RAY DIFFRACTION	1.89
5IU7	X-RAY DIFFRACTION	1.9
5K2C	X-RAY DIFFRACTION	1.9
5K2D	X-RAY DIFFRACTION	1.9
5OLZ	X-RAY DIFFRACTION	1.9
7IOF	X-RAY DIFFRACTION	1.9
7IPF	X-RAY DIFFRACTION	1.9
7IO9	X-RAY DIFFRACTION	1.91
6ZDR	X-RAY DIFFRACTION	1.92
7IOP	X-RAY DIFFRACTION	1.92
8RW0	X-RAY DIFFRACTION	1.94
5NM2	X-RAY DIFFRACTION	1.95
7IP5	X-RAY DIFFRACTION	1.95
7IO2	X-RAY DIFFRACTION	1.96
7IOG	X-RAY DIFFRACTION	1.98
7IP0	X-RAY DIFFRACTION	1.99
5OLV	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29274-F1	81.30	0.65

Antibody-complex structures (SAbDab): 8 — 3VG9, 3VGA, 6GDG, 8GNG, 8WDT, 9EE8, 9EE9, 9EEA

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 169; 253; 277; 278

Disulfide bonds (4): 71–159, 74–146, 77–166, 259–262

Glycosylation sites (1): 154

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-187024	NGF-independant TRKA activation
R-HSA-417973	Adenosine P1 receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-5683826	Surfactant metabolism
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187015	Activation of TRKA receptors
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-392499	Metabolism of proteins
R-HSA-418038	Nucleotide-like (purinergic) receptors
R-HSA-500792	GPCR ligand binding
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 442 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, MODULE_92, GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_GLUTAMATE_SECRETION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_AMINE, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (53): synaptic transmission, dopaminergic (GO:0001963), G protein-coupled adenosine receptor signaling pathway (GO:0001973), response to amphetamine (GO:0001975), regulation of DNA-templated transcription (GO:0006355), phagocytosis (GO:0006909), apoptotic process (GO:0006915), inflammatory response (GO:0006954), cellular defense response (GO:0006968), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), cell-cell signaling (GO:0007267), synaptic transmission, cholinergic (GO:0007271), central nervous system development (GO:0007417), blood coagulation (GO:0007596), sensory perception (GO:0007600), locomotory behavior (GO:0007626), blood circulation (GO:0008015), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), positive regulation of glutamate secretion (GO:0014049), positive regulation of acetylcholine secretion, neurotransmission (GO:0014057), regulation of norepinephrine secretion (GO:0014061), response to purine-containing compound (GO:0014074), response to caffeine (GO:0031000), positive regulation of synaptic transmission, GABAergic (GO:0032230), synaptic transmission, glutamatergic (GO:0035249), positive regulation of urine volume (GO:0035810), vasodilation (GO:0042311), eating behavior (GO:0042755), negative regulation of vascular permeability (GO:0043116), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of circadian sleep/wake cycle, sleep (GO:0045938), negative regulation of alpha-beta T cell activation (GO:0046636), astrocyte activation (GO:0048143), neuron projection morphogenesis (GO:0048812), positive regulation of protein secretion (GO:0050714), negative regulation of inflammatory response (GO:0050728), regulation of mitochondrial membrane potential (GO:0051881), membrane depolarization (GO:0051899)

GO Molecular Function (10): G protein-coupled adenosine receptor activity (GO:0001609), calmodulin binding (GO:0005516), lipid binding (GO:0008289), enzyme binding (GO:0019899), type 5 metabotropic glutamate receptor binding (GO:0031802), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), alpha-actinin binding (GO:0051393), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (12): intermediate filament (GO:0005882), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), axolemma (GO:0030673), asymmetric synapse (GO:0032279), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), postsynaptic membrane (GO:0045211), presynaptic active zone (GO:0048786), glutamatergic synapse (GO:0098978), axon (GO:0030424)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Signal Transduction	2
Signaling by GPCR	2
Activation of TRKA receptors	1
Nucleotide-like (purinergic) receptors	1
GPCR downstream signalling	1
Metabolism of proteins	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRK1 (TRKA)	1
Signaling by NTRKs	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
protein binding	3
binding	3
chemical synaptic transmission	2
defense response	2
cellular anatomical structure	2
neuron projection	2
synaptic membrane	2
presynapse	2
G protein-coupled purinergic receptor signaling pathway	1
response to amine	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
endocytosis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
cell communication	1
signaling	1
nervous system development	1
system development	1
hemostasis	1
wound healing	1
coagulation	1
nervous system process	1
behavior	1
circulatory system process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to chemical	1
G protein-coupled adenosine receptor signaling pathway	1
G protein-coupled receptor activity	1
G protein-coupled glutamate receptor binding	1
actinin binding	1

Protein interactions and networks

STRING

1980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADORA2A	DRD2	P14416	987
ADORA2A	GRM5	P41594	968
ADORA2A	CNR1	P21554	884
ADORA2A	NT5E	P21589	869
ADORA2A	ADA	P00813	864
ADORA2A	ENTPD1	P49961	862
ADORA2A	NTRK2	Q16620	809
ADORA2A	DPP4	P27487	767
ADORA2A	TMTC1	Q8IUR5	728
ADORA2A	ADCY5	O95622	725
ADORA2A	FGFR1	P11362	717
ADORA2A	SLC29A1	Q99808	715
ADORA2A	CTLA4	P16410	698
ADORA2A	PRKACA	P17612	697
ADORA2A	PRKACB	P22694	697

IntAct

88 interactions, top by confidence:

A	B	Type	Score
ADORA2A	ADORA2A	psi-mi:“MI:2364”(proximity)	0.750
ADORA2A	ADORA2A	psi-mi:“MI:0915”(physical association)	0.750
ADORA2A	NECAB2	psi-mi:“MI:0915”(physical association)	0.710
NECAB2	ADORA2A	psi-mi:“MI:0407”(direct interaction)	0.710
ADORA2A	NECAB2	psi-mi:“MI:0407”(direct interaction)	0.710
NECAB2	ADORA2A	psi-mi:“MI:0403”(colocalization)	0.710
ADORA2A	DRD2	psi-mi:“MI:2364”(proximity)	0.680
ADORA2A	CNR1	psi-mi:“MI:0915”(physical association)	0.680
CNR1	ADORA2A	psi-mi:“MI:2364”(proximity)	0.680
CNR1	ADORA2A	psi-mi:“MI:0403”(colocalization)	0.680
DRD2	ADORA2A	psi-mi:“MI:2364”(proximity)	0.680
DRD2	ADORA2A	psi-mi:“MI:0403”(colocalization)	0.680
ADORA2A	CYTH2	psi-mi:“MI:0915”(physical association)	0.630
ADORA2A	CYTH2	psi-mi:“MI:0407”(direct interaction)	0.630

BioGRID (40): CYTH2 (Two-hybrid), ADORA2A (Reconstituted Complex), CYTH2 (Affinity Capture-Western), DRD2 (Affinity Capture-Western), ADORA2A (FRET), DRD2 (FRET), GRM5 (Affinity Capture-Western), ADORA2A (Affinity Capture-Western), NECAB2 (Two-hybrid), ADORA2A (Reconstituted Complex), NECAB2 (Affinity Capture-Western), ADORA2A (Affinity Capture-Western), ADORA2A (Reconstituted Complex), ADORA2A (Two-hybrid), ADORA2A (Two-hybrid)

ESM2 similar proteins: A0A2R9YJI3, A1ZAX0, B2ZHY2, B4XF06, D4A3U0, O43194, O46635, O55040, O88319, P08911, P08912, P0C0W8, P11617, P14842, P18599, P20789, P28223, P29274, P30543, P30989, P32940, P34979, P35363, P35408, P46616, P50128, P50129, P56490, P70259, Q58CW4, Q5IS53, Q5IS98, Q5R4Q6, Q5U431, Q60613, Q6DWJ6, Q6TLI7, Q75Z89, Q7TQN9, Q8BZ39

Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, F1MV99, G4WMX4, O02835, O02836, O08725, O42179, O43614, O54799, O62729, O62809, O70342, O77408, P0DQD5, P11617, P20288, P22270, P24053, P24628, P25929, P25931, P28336, P29274, P30731, P30938, P30975, P32251, P35346, P35371, P41143, P47211, P47751, P49146, P49219, P49285, P49288, P49683, P50391

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
ADORA2A	“up-regulates activity”	GNAS	binding
ADORA2A	“up-regulates activity”	GNAL	binding
ADORA2A	“up-regulates activity”	GNAI1	binding
ADORA2A	“up-regulates activity”	GNAI3	binding
ADORA2A	“up-regulates activity”	GNAO1	binding
ADORA2A	“up-regulates activity”	GNAZ	binding
ADORA2A	“up-regulates activity”	GNAQ	binding
ADORA2A	“up-regulates activity”	GNA14	binding
adenosine	“up-regulates activity”	ADORA2A	“chemical activation”
adenosine	“up-regulates activity”	ADORA2A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (i) signalling events	5	10.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	24.6×	1e-04
G protein-coupled receptor signaling pathway	8	12.6×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

123 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	7
Uncertain significance	83
Likely benign	3
Benign	6

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
148861	GRCh38/hg38 22q11.21-12.3(chr22:20907226-37187347)x3	Pathogenic
149114	GRCh38/hg38 22q11.23-12.3(chr22:23279231-36247369)x3	Pathogenic
1703645	GRCh37/hg19 22q11.21-11.23(chr22:21798906-25039018)	Pathogenic
1808230	GRCh37/hg19 22q11.22-11.23(chr22:22997929-24995256)x3	Pathogenic
253485	GRCh37/hg19 22q11.22-11.23(chr22:22976696-25053311)x3	Pathogenic
2580295	GRCh37/hg19 22q11.23(chr22:23658260-25114888)x3	Pathogenic
3148891	GRCh37/hg19 22q11.23(chr22:23652549-25002659)x3	Pathogenic
395052	GRCh37/hg19 22q11.22-11.23(chr22:23258229-25046758)x3	Pathogenic
441826	GRCh37/hg19 22q11.23-12.3(chr22:23637907-36614412)x3	Pathogenic
565045	GRCh37/hg19 22q11.21-11.23(chr22:21465661-24885806)x1	Pathogenic
565055	GRCh37/hg19 22q11.22-12.3(chr22:22460754-35198232)x3	Pathogenic
57132	GRCh38/hg38 22q11.21-12.3(chr22:18178957-31821193)x3	Pathogenic
685636	GRCh37/hg19 22q11.1-13.33(chr22:16888899-51197838)x3	Pathogenic
685920	GRCh37/hg19 22q11.22-11.23(chr22:22962195-25002659)x3	Pathogenic
686931	GRCh37/hg19 22q11.22-11.23(chr22:22962196-25059631)x3	Pathogenic
688543	GRCh37/hg19 22q11.23(chr22:23650200-25066472)x3	Pathogenic
688980	GRCh37/hg19 22q11.23(chr22:23698818-25042987)x3	Pathogenic
816203	GRCh37/hg19 22q11.21-11.23(chr22:20732808-25193541)x3	Pathogenic
830686	NC_000022.10:g.(?24129357)(24836024_?)del	Pathogenic
979598	GRCh37/hg19 22q11.22-11.23(chr22:23258368-25059827)x3	Pathogenic
979600	GRCh37/hg19 22q11.23(chr22:23650873-25043046)x3	Pathogenic
1808733	GRCh37/hg19 22q11.22-11.23(chr22:22953515-24995256)x3	Likely pathogenic
219016	GRCh37/hg19 22q11.23(chr22:23891773-24991691)x3	Likely pathogenic
545272	Single allele	Likely pathogenic
545274	Single allele	Likely pathogenic
545275	Single allele	Likely pathogenic
565019	GRCh37/hg19 22q11.23(chr22:23650871-25002659)x3	Likely pathogenic
625627	GRCh37/hg19 22q11.23(chr22:23653987-25158391)	Likely pathogenic

SpliceAI

896 predictions. Top by Δscore:

Variant	Effect	Δscore
22:24423955:C:T	donor_gain	0.9900
22:24427743:GGGG:G	donor_gain	0.9900
22:24427744:GGGG:G	donor_gain	0.9900
22:24440579:CCAGG:C	acceptor_loss	0.9900
22:24440580:CAGGT:C	acceptor_loss	0.9900
22:24440581:A:AG	acceptor_gain	0.9900
22:24440581:AGGT:A	acceptor_loss	0.9900
22:24440582:G:GG	acceptor_gain	0.9900
22:24440582:G:GT	acceptor_loss	0.9900
22:24423955:CAG:C	donor_loss	0.9800
22:24423956:AG:A	donor_loss	0.9800
22:24423957:GGT:G	donor_loss	0.9800
22:24423958:G:GC	donor_loss	0.9800
22:24423967:GGTGC:G	donor_gain	0.9800
22:24426377:GC:G	donor_gain	0.9800
22:24427744:GGG:G	donor_gain	0.9800
22:24427745:GG:G	donor_gain	0.9800
22:24427745:GGG:G	donor_gain	0.9800
22:24427746:GG:G	donor_gain	0.9800
22:24433126:TGCA:T	acceptor_loss	0.9800
22:24433127:GCAG:G	acceptor_loss	0.9800
22:24433128:CA:C	acceptor_loss	0.9800
22:24433128:CAG:C	acceptor_loss	0.9800
22:24433129:A:AC	acceptor_loss	0.9800
22:24433129:A:AG	acceptor_gain	0.9800
22:24433129:A:C	acceptor_loss	0.9800
22:24433130:G:A	acceptor_loss	0.9800
22:24433130:G:C	acceptor_loss	0.9800
22:24433130:G:GG	acceptor_gain	0.9800
22:24433734:CCGG:C	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000221784 (22:24434541 GTCAGAGGCCTTCTGC>G), RS1000247210 (22:24436637 A>G), RS1000360483 (22:24436902 G>A), RS1000380359 (22:24430731 G>A), RS1000393741 (22:24431249 G>A), RS1000467731 (22:24436325 C>A,G,T), RS1000707640 (22:24436149 C>T), RS1001101150 (22:24442472 G>A,T), RS1001210377 (22:24427193 C>T), RS1001477358 (22:24438030 C>T), RS1001499965 (22:24424446 AG>A), RS1001593267 (22:24431778 C>T), RS1001672742 (22:24422715 G>A), RS1001783870 (22:24424592 C>G,T), RS1001916541 (22:24438135 C>T)

Disease associations

OMIM: gene MIM:102776 | disease phenotypes: MIM:608363, MIM:181500

GenCC curated gene-disease

Mondo (4): chromosome 22q11.2 microduplication syndrome (MONDO:0012020), renal agenesis, unilateral (MONDO:0019636), primary ovarian failure (MONDO:0005387), schizophrenia (MONDO:0005090)

Orphanet (4): 22q11.2 duplication syndrome (Orphanet:1727), Renal agenesis, unilateral (Orphanet:93100), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

12 total (13 of 12 shown, HPO-id order):

HPO	Term
HP:0002069	Bilateral tonic-clonic seizure
HP:0007103	Hypointensity of cerebral white matter on MRI
HP:0007185	Loss of consciousness
HP:0007738	Uncontrolled eye movements
HP:0011172	Complex febrile seizure
HP:0011665	Takotsubo cardiomyopathy
HP:0012705	Abnormal metabolic brain imaging by MRS
HP:0031475	Status epilepticus without prominent motor symptoms
HP:0031691	Severe viral infection
HP:0032308	Increased circulating procalcitonin concentration
HP:0032894	Seizure precipitated by febrile infection
HP:0033349	Seizure cluster
HP:0100753	Schizophrenia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002481_6	Acne (severe)	6.000000e-07
GCST003116_7	Coronary artery disease	2.000000e-10
GCST004787_72	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	7.000000e-10
GCST005929_5	Severity of nausea and vomiting of pregnancy	6.000000e-09
GCST008028_4	Coffee consumption (cups per day)	1.000000e-12
GCST008028_8	Coffee consumption (cups per day)	4.000000e-07
GCST008028_9	Coffee consumption (cups per day)	3.000000e-06
GCST011124_11	Caffeine consumption from tea	7.000000e-29
GCST011126_36	Caffeine consumption from coffee or tea	3.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009265	nausea and vomiting of pregnancy severity measurement
EFO:0006782	cups of coffee per day measurement
EFO:0010091	tea consumption measurement
EFO:0006781	coffee consumption measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C567224	Chromosome 22q11.2 Microduplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2094257 (PROTEIN FAMILY), CHEMBL2095213 (SELECTIVITY GROUP), CHEMBL2096679 (SELECTIVITY GROUP), CHEMBL2096982 (SELECTIVITY GROUP), CHEMBL2111329 (PROTEIN FAMILY), CHEMBL251 (SINGLE PROTEIN), CHEMBL4296621 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

81 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,301,739 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL113	CAFFEINE	4	200,591
CHEMBL1355736	THEOPHYLLINE	4	752
CHEMBL477	ADENOSINE	4	222,014
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201346	BALSALAZIDE	4	8,319
CHEMBL1282	IMIQUIMOD	4	56,604
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL146095	GLAFENINE	4	2,714
CHEMBL1467	ALLOPURINOL	4	85,212
CHEMBL1475	TRIOXSALEN	4	219,770
CHEMBL1580	PENTOSTATIN	4	103,826
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL1726	NISOLDIPINE	4	18,921
CHEMBL1750	CLOFARABINE	4	31,786
CHEMBL178	DAUNORUBICIN	4	203,756
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL193	NIFEDIPINE	4
CHEMBL19449	IBUDILAST	4
CHEMBL290106	BITHIONOL	4
CHEMBL317052	REGADENOSON ANHYDROUS	4
CHEMBL3353410	OSIMERTINIB	4
CHEMBL374478	RIFAMPIN	4
CHEMBL405	AMPHETAMINE	4
CHEMBL411	DIETHYLSTILBESTROL	4
CHEMBL416956	MEFLOQUINE	4
CHEMBL431770	ISTRADEFYLLINE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

9 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2236624	Toxicity	3	methotrexate	adverse events;Rheumatoid arthritis
rs2267076	Toxicity	3	methotrexate	Rheumatoid arthritis
rs2298383	Toxicity	3	caffeine
rs2298383	Toxicity	3	methotrexate	Rheumatoid arthritis
rs2298383	Toxicity	3	methotrexate	Hematologic Neoplasms
rs3761422	Toxicity	3	methotrexate	Rheumatoid arthritis
rs3761422	Toxicity	3	caffeine	Anxiety Disorders
rs5751876	Toxicity	3	caffeine	Anxiety Disorders
rs5760410	Toxicity	3	methotrexate	Rheumatoid arthritis

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2236624	ADORA2A, ADORA2A-AS1	3	1.75	1	methotrexate
rs2267076	ADORA2A, ADORA2A-AS1	3	2.75	1	methotrexate
rs2298383	ADORA2A, ADORA2A-AS1	3	2.25	3	methotrexate;caffeine
rs3032740	ADORA2A, ADORA2A-AS1		0.00	0
rs3761422	ADORA2A, ADORA2A-AS1	3	2.75	2	methotrexate;caffeine
rs5751876	ADORA2A, ADORA2A-AS1	3	5.00	1	caffeine
rs5760410	ADORA2A, SPECC1L	3	2.75	1	methotrexate
rs5996696	ADORA2A, ADORA2A-AS1		0.00	0
rs11704959	ADORA2A		0.00	0
rs35320474	ADORA2A, ADORA2A-AS1		0.00	0
rs71651683	ADORA2A, ADORA2A-AS1		0.00	0
rs35060421	ADORA2A, ADORA2A-AS1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Adenosine receptors

Most potent curated ligand interactions (100 total), top 25:

Ligand	Action	Affinity	Parameter
SCH442416	Antagonist	10.3	pKi
CGS 15943	Antagonist	9.4	pKi
apadenoson	Agonist	9.3	pKi
MRS1093	Antagonist	9.2	pKi
[125I]ZM-241385	Antagonist	9.2	pKd
SCH 58261	Antagonist	9.2	pKi
ZM-241385	Antagonist	9.1	pKi
[3H]ZM 241385	Antagonist	9.1	pKd
preladenant	Antagonist	9.05	pKi
xanthine amine congener	Antagonist	9.0	pKi
[3H]SCH 58261	Antagonist	9.0	pKd
vipadenant	Antagonist	8.89	pKi
imaradenant	Antagonist	8.77	pKi
NECA	Full agonist	8.7	pKi
(R,S)-PHPNECA	Full agonist	8.5	pKi
tozadenant	Antagonist	8.3	pKi
UK-432,097	Agonist	8.3	pKi
2-hexynyl-NECA	Full agonist	8.3	pKi
MSX-2	Antagonist	8.27	pKi
ST-1535	Antagonist	8.18	pKi
compound 4g [PMID: 22220592]	Agonist	8.11	pKi
CGS 21680	Full agonist	8.1	pKi
[3H]XAC	Antagonist	8.0	pKd
istradefylline	Antagonist	7.92	pKi
[3H]CGS 21680	Full agonist	7.8	pKd

Binding affinities (BindingDB)

1148 measured of 1248 human assays (1301 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[4-[2-amino-3,5-dicyano-6-[[2-(methylcarbamoyl)-4-pyridinyl]methylsulfanyl]-4-pyridinyl]phenyl] N,N-dimethylsulfamate	EC50	0.04 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-4-[4-(2-aminoethoxy)phenyl]-3,5-dicyano-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.04 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.06 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]-N-cyclopropylpyridine-2-carboxamide	EC50	0.08 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-[4-(2-hydroxy-2-methylpropoxy)phenyl]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.1 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-4-[6-(2-hydroxyethoxy)-3-pyridinyl]-6-(2-hydroxyethylamino)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.1 nM	US-9187428: Substituted dicyanopyridines and use thereof
1-[4-[(3R)-3-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)piperidin-1-yl]-5-methylpyrazol-1-yl]-2-methylpropan-2-ol	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2-[(3R)-1-[5-methyl-1-(oxan-4-yl)pyrazol-4-yl]piperidin-3-yl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2-[(3R)-1-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]piperidin-3-yl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
1-[3-[(3R)-3-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)piperidin-1-yl]-1,2,4-triazol-1-yl]-2-methylpropan-2-ol	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2-[(3R)-1-[6-(trifluoromethyl)pyrazin-2-yl]piperidin-3-yl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2-[(3R)-1-(5-methylpyrazin-2-yl)piperidin-3-yl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
2-[(3R)-1-[1-(1,1-dioxothian-4-yl)pyrazol-4-yl]piperidin-3-yl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
1-[4-[(5R)-5-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-3,3-difluoropiperidin-1-yl]-5-methylpyrazol-1-yl]-2-methylpropan-2-ol	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2-[1-(1-methyltriazol-4-yl)azepan-3-yl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
The Preparation of the Compounds of Examples 210A and 210B	IC50	0.1 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2- [(1r,2r)-2- phenylcyclopropyl] [1,2,4]triazolo[1,5-c] quinazolin-5- amine	IC50	0.1 nM	US-20250171447: ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE THEREOF
8-methyl-7-(1,3-oxazol-2-yl)-2-[2-(1-propan-2-yl-6,7-dihydro-4H-triazolo[4,5-c]pyridin-5-yl)ethyl]-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine	IC50	0.1 nM	US-12414952: Substituted amino triazolopyrimidine and amino triazolopyrazine adenosine receptor antagonists, pharmaceutical compositions and their use
4-[[6-amino-3,5-dicyano-4-(4-methoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(4-ethoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(3,5-difluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-(3-hydroxyazetidin-1-yl)-4-phenyl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-[2-hydroxyethyl(methyl)amino]-4-phenyl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-4-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-[(3R)-3-hydroxypyrrolidin-1-yl]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-[[(2S)-2,3-dihydroxypropyl]amino]-4-phenyl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
3-[[3,5-dicyano-4-[4-(2-hydroxyethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-2-pyridinyl]sulfanylmethyl]-N-methylbenzamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
3-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]-N-(2-aminoethyl)benzamide	EC50	0.2 nM	US-9187428: Substituted dicyanopyridines and use thereof
2-amino-N-[(3,6- dimethyl-2- pyridyl)methyl]-8- methoxy-quinazoline-4- carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-amino-N-[(1-ethyl-2- oxo-3-pyridyl)methyl]-8- methoxy-quinazoline-4- carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-amino-8-methoxy-N-(quinolin-8-ylmethyl)quinazoline-4-carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-amino-N-(quinolin-8-ylmethyl)-8-(trifluoromethoxy)quinazoline-4-carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-amino-N-[(6-cyclobutyl-2-pyridinyl)methyl]-8-methoxyquinazoline-4-carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-amino-8-methoxy-N-[(6-propan-2-yl-2-pyridinyl)methyl]quinazoline-4-carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-amino-N-[[6-[(2-fluorophenoxy)methyl]-2-pyridinyl]methyl]-8-methoxyquinazoline-4-carboxamide	KI	0.2 nM	US-10138212: Aminoquinazoline compounds as A2A antagonist
2-[(3R)-1-[5-(difluoromethyl)-1-(oxan-4-yl)pyrazol-4-yl]piperidin-3-yl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
(1S)-2-[4-[(3R)-3-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)piperidin-1-yl]pyrazol-1-yl]cyclopentan-1-ol	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
(1R)-2-[4-[(3R)-3-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)piperidin-1-yl]pyrazol-1-yl]cyclopentan-1-ol	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
(3R)-3-[4-[(3R)-3-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)piperidin-1-yl]pyrazol-1-yl]-2-methylbutan-2-ol	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
7-methoxy-2-[(3R)-1-(5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)piperidin-3-yl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
3-[4-[(2S,5R)-5-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-2-methylpiperidin-1-yl]pyrazol-1-yl]-2-methylbutan-2-ol	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
The Preparation of the Compounds of Examples 210A and 210B	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
2-[4-[(2S,5R)-5-(5-amino-8-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-2-methylpiperidin-1-yl]pyrazol-1-yl]-2-methylpropan-1-ol	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
3-[4-[(3R,5R)-3-(5-amino-8-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-5-methylpiperidin-1-yl]-3-methylpyrazol-1-yl]butan-2-ol	IC50	0.2 nM	US-12263171: 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use
N-[4-(3-Cyanophenyl)-5-(4-methoxyquinazolin-6-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	0.2 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-pyrazolo[1,5-a]pyridin-5-yl-thiazol-2-yl]morpholine-4-carboxamide	KI	0.2 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
1-[4-[[8-amino-5-methyl-6-(1,3-oxazol-2-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl]methyl]benzimidazol-1-yl]-2-methylpropan-2-ol	IC50	0.2 nM	US-12414952: Substituted amino triazolopyrimidine and amino triazolopyrazine adenosine receptor antagonists, pharmaceutical compositions and their use
4-[[6-amino-3,5-dicyano-4-(4-fluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.3 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(3,4-difluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.3 nM	US-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(4-fluoro-3-methoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamide	EC50	0.3 nM	US-9187428: Substituted dicyanopyridines and use thereof
3-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]benzamide	EC50	0.3 nM	US-9187428: Substituted dicyanopyridines and use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL2419139
10.96	IC50	0.011	nM	CHEMBL4167125
10.80	Ki	0.016	nM	CHEMBL1092271
10.57	Ki	0.027	nM	CHEMBL2419146
10.52	Ki	0.03	nM	CHEMBL2419147
10.52	Ki	0.03	nM	CHEMBL336608
10.44	IC50	0.036	nM	CHEMBL4161758
10.44	IC50	0.036	nM	CHEMBL5182250
10.42	Ki	0.038	nM	CHEMBL1090578
10.40	IC50	0.04	nM	CHEMBL4172399
10.39	Kd	0.04058	nM	CHEMBL2024114
10.38	Ki	0.042	nM	CHEMBL3121727
10.35	Ki	0.045	nM	CHEMBL3121725
10.35	IC50	0.045	nM	CHEMBL4172264
10.32	Ki	0.048	nM	CHEMBL136689
10.30	Ki	0.05	nM	CHEMBL337080
10.29	IC50	0.051	nM	CHEMBL3958838
10.23	IC50	0.059	nM	CHEMBL4167125
10.22	Ki	0.06	nM	CHEMBL4217582
10.17	Ki	0.067	nM	CHEMBL2419150
10.15	Ki	0.07	nM	CHEMBL4217248
10.15	IC50	0.07	nM	CHEMBL5815348
10.14	Ki	0.072	nM	CHEMBL3121726
10.11	Ki	0.078	nM	CHEMBL4747929
10.10	IC50	0.08	nM	CHEMBL5888877
10.10	Ki	0.08	nM	CHEMBL131242
10.09	Ki	0.081	nM	CHEMBL5203105
10.05	IC50	0.09	nM	CHEMBL5759493
10.02	IC50	0.095	nM	CHEMBL3904408
10.00	Ki	0.1	nM	CHEMBL2165801
10.00	Ki	0.1	nM	CHEMBL1095999
10.00	Ki	0.1	nM	ZM-241385
10.00	Ki	0.1	nM	CHEMBL245848
10.00	IC50	0.1	nM	CHEMBL5999728
10.00	IC50	0.1	nM	CHEMBL5928153
10.00	IC50	0.1	nM	CHEMBL5940119
10.00	IC50	0.1	nM	CHEMBL5836704
10.00	IC50	0.1	nM	CHEMBL5747460
10.00	IC50	0.1	nM	CHEMBL5826102
10.00	Ki	0.1	nM	CHEMBL369573
10.00	Ki	0.1	nM	CHEMBL130830
9.96	Ki	0.11	nM	CHEMBL4778265
9.92	Ki	0.12	nM	CHEMBL22202
9.92	Ki	0.12	nM	CHEMBL3121728
9.92	Ki	0.12	nM	CHEMBL22717
9.92	Ki	0.12	nM	CHEMBL1092270
9.89	Ki	0.13	nM	CHEMBL22320
9.87	Kd	0.1349	nM	CHEMBL506250
9.85	Ki	0.14	nM	CHEMBL2419140
9.85	IC50	0.14	nM	CHEMBL5909324

PubChem BioAssay actives

2702 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6,7-dimethoxy-4H-indeno[1,2-d][1,3]thiazol-2-amine;hydroiodide	33156: AE maximal score at Adenosine A2A receptor	ec50	<0.0001	uM
4-(furan-2-yl)-10-[3-(4-methoxyphenyl)propyl]-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine	1181333: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cells	ki	<0.0001	uM
2-(furan-2-yl)-5-N-[(2-methoxyphenyl)methyl]-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1338763: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method	ic50	<0.0001	uM
2-(furan-2-yl)-5-N-[(3-methoxyphenyl)methyl]-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1338763: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method	ic50	<0.0001	uM
2-(furan-2-yl)-5-N-(thiophen-2-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360948: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method	ic50	<0.0001	uM
2-(furan-2-yl)-5-N-(2-thiophen-2-ylethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360948: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method	ic50	<0.0001	uM
2-(furan-2-yl)-5-N-(pyridin-3-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360948: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method	ic50	<0.0001	uM
2-(furan-2-yl)-5-N-(furan-2-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360948: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method	ic50	<0.0001	uM
2-[4-[2-[7-amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]ethyl]-N-(2-hydroxyethyl)anilino]ethanol	34373: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells.	ki	0.0001	uM
2-amino-4-phenylindeno[1,2-d]pyrimidin-5-one	479267: Antagonist activity at adenosine A2A receptor	ki	0.0001	uM
10-[3-[4-(aminomethyl)phenyl]propyl]-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine	34373: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells.	ki	0.0001	uM
2-amino-4-(furan-2-yl)indeno[1,2-d]pyrimidin-5-one	1138022: Antagonist activity at human recombinant adenosine receptor A2a by cAMP assay	ki	0.0001	uM
4-[2-[7-amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]ethyl]-N,N-bis(2-hydroxyethyl)benzenesulfonamide	365580: Binding affinity to human adenosine A2A receptor	ki	0.0001	uM
4-amino-2-(furan-2-yl)-6-[(2S)-2-hydroxypropoxy]-N-[(3-methyl-2-pyridinyl)methyl]pyrimidine-5-carboxamide	1696180: Inhibition of FRET-labelled CA200645 binding to human adenosine 2A receptor expressed in CHO cells incubated for 2 hr by TR-FRET assay	ki	0.0001	uM
[5-[3-[7-amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]propyl]-2-(hydroxymethyl)-1,3-benzodioxol-2-yl]methanol	34374: Displacement of [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells; ranges from 0.16-0.21	ki	0.0002	uM
4-[2-[7-amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]ethyl]-N’-hydroxybenzenecarboximidamide	34373: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells.	ki	0.0002	uM
4-(furan-2-yl)-11-(3-phenylpropyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine	34249: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells	ki	0.0002	uM
10-[3-(4-aminophenyl)propyl]-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine	34234: Binding affinity against WT human adenosine A2A receptor expressed in CHO cells using [3H]- ZM-241385	ki	0.0002	uM
5-[(7S,9aS)-7-[(3-fluorophenoxy)methyl]-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amine	365580: Binding affinity to human adenosine A2A receptor	ki	0.0002	uM
2-amino-N-[(6-cyclobutyl-2-pyridinyl)methyl]-8-methoxyquinazoline-4-carboxamide	1325764: Displacement of [3H]5-amino-7-[2- phenethyl]-2-(furan-2-yl)-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine from human adenosine A2A receptor expressed in HEK293 cell membranes measured after 1 hr by TopCount scintillation counting method	ki	0.0002	uM
2-amino-8-methoxy-N-(quinolin-8-ylmethyl)quinazoline-4-carboxamide	1277493: Displacement of [3H]SCH-58261 from human adenosine A2A receptor expressed in HEK cell membranes after 60 mins by microplate scintillation counting analysis	ki	0.0002	uM
2-amino-8-methoxy-N-[(6-propan-2-yl-2-pyridinyl)methyl]quinazoline-4-carboxamide	1325764: Displacement of [3H]5-amino-7-[2- phenethyl]-2-(furan-2-yl)-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine from human adenosine A2A receptor expressed in HEK293 cell membranes measured after 1 hr by TopCount scintillation counting method	ki	0.0002	uM
2-amino-N-(quinolin-8-ylmethyl)-8-(trifluoromethoxy)quinazoline-4-carboxamide	1277493: Displacement of [3H]SCH-58261 from human adenosine A2A receptor expressed in HEK cell membranes after 60 mins by microplate scintillation counting analysis	ki	0.0002	uM
2-amino-N-[[6-[(2-fluorophenoxy)methyl]-2-pyridinyl]methyl]-8-methoxyquinazoline-4-carboxamide	1325764: Displacement of [3H]5-amino-7-[2- phenethyl]-2-(furan-2-yl)-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine from human adenosine A2A receptor expressed in HEK293 cell membranes measured after 1 hr by TopCount scintillation counting method	ki	0.0002	uM
4-(diethylamino)-N-(4-methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)-1-methylcyclohexane-1-carboxamide	1436484: Antagonist activity at human adenosine A2A receptor expressed in HEK293 cell membranes assessed as decrease in CGS-21680/forskolin-induced cAMP level pretreated for 15 mins followed by agonist addition for 30 mins and subsequent forskolin stimulation measured after 30 mins	ki	0.0002	uM
4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2,6-dimethylphenol	659094: Binding affinity to adenosine A2A receptor by surface plasmon resonance	kd	0.0002	uM
2-(furan-2-yl)-5-N-(2-pyridin-3-ylethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360945: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in CHO cell membranes measured after 60 mins by scintillation counting method	ki	0.0002	uM
8-amino-6-(4-methoxy-3,5-dimethylphenyl)-2-phenyl-[1,2,4]triazolo[4,3-a]pyrazin-3-one	1525824: Displacement of [3H]NECA from human adenosine A2A receptor expressed in CHO cell membranes by radioligand competition assay	ki	0.0002	uM
4-(furan-2-yl)-10-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine	607198: Displacement of [3H]ZM241385 from stabilized human adenosine receptor A2a expressed in HEK293 cells followed by receptor capturing on Biocore chips by SPR method	kd	0.0003	uM
4-(furan-2-yl)-11-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine	34249: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells	ki	0.0003	uM
4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)-4-methylpiperidine-1-carboxamide	1436484: Antagonist activity at human adenosine A2A receptor expressed in HEK293 cell membranes assessed as decrease in CGS-21680/forskolin-induced cAMP level pretreated for 15 mins followed by agonist addition for 30 mins and subsequent forskolin stimulation measured after 30 mins	ki	0.0003	uM
2-amino-7-fluoro-N-(quinolin-8-ylmethyl)quinazoline-4-carboxamide	1277493: Displacement of [3H]SCH-58261 from human adenosine A2A receptor expressed in HEK cell membranes after 60 mins by microplate scintillation counting analysis	ki	0.0003	uM
4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorophenol	659094: Binding affinity to adenosine A2A receptor by surface plasmon resonance	kd	0.0003	uM
4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)-1,4-dimethylcyclohexane-1-carboxamide	1436484: Antagonist activity at human adenosine A2A receptor expressed in HEK293 cell membranes assessed as decrease in CGS-21680/forskolin-induced cAMP level pretreated for 15 mins followed by agonist addition for 30 mins and subsequent forskolin stimulation measured after 30 mins	ki	0.0003	uM
2-(furan-2-yl)-5-N-(thiophen-3-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360945: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in CHO cell membranes measured after 60 mins by scintillation counting method	ki	0.0003	uM
5-[5-amino-2-[(3-chloro-5-fluoro-2-pyridinyl)methyl]-7-phenyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]-1H-pyridin-2-one	1782625: Antagonist activity at human A2aR expressed in CHO-K1 cells assessed as inhibition of cAMP accumulation preincubated for 30 mins followed by adenosine addition and measured for 30 mins by HTRF assay	ic50	0.0003	uM
5-[5-amino-7-(4-fluorophenyl)-2-[(5-fluoro-2-pyridinyl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]-1H-pyridin-2-one	1782625: Antagonist activity at human A2aR expressed in CHO-K1 cells assessed as inhibition of cAMP accumulation preincubated for 30 mins followed by adenosine addition and measured for 30 mins by HTRF assay	ic50	0.0003	uM
10-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine	306061: Binding affinity to human adenosine A2A receptor	ki	0.0004	uM
4-[[2-[[6-(2,2-diphenylethylamino)-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purine-2-carbonyl]amino]ethylcarbamoylamino]methyl]benzoic acid	477377: Agonist activity at adenosine A2A receptor in fMLP-stimulated human neutrophils assessed as inhibition of superoxide production by colorimetric analysis	ic50	0.0004	uM
(2R,3R,4S,5R)-2-[6-[[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	30507: Coronary arteries vasodilation at the adenosine A2 receptor in langendorff guinea pig heart preparation	ec50	0.0004	uM
ethyl 2-[4-[2-[7-amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]ethyl]phenoxy]acetate	34373: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells.	ki	0.0004	uM
2-amino-8-methoxy-N-[[6-(trifluoromethyl)-2-pyridinyl]methyl]quinazoline-4-carboxamide	1325764: Displacement of [3H]5-amino-7-[2- phenethyl]-2-(furan-2-yl)-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine from human adenosine A2A receptor expressed in HEK293 cell membranes measured after 1 hr by TopCount scintillation counting method	ki	0.0004	uM
2-(furan-2-yl)-5-N-(pyridin-2-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-5,7-diamine	1360945: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in CHO cell membranes measured after 60 mins by scintillation counting method	ki	0.0004	uM
5-amino-8-(furan-2-yl)-3-[2-[4-[4-(1-methoxypropan-2-yloxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one	1379297: Displacement of [3H]ZM241385 from human A2A receptor expressed in HEK293 cell membranes after 90 mins radioligand binding assay	ki	0.0004	uM
5-amino-3-[2-[4-[3-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-(1,3-thiazol-2-yl)-[1,2,4]triazolo[5,1-f]purin-2-one	1379300: Antagonist activity at human A2A receptor expressed in HEK293 cell membranes assessed as reduction in CGS-21680-induced cAMP level pretreated for 15 mins followed by CGS-21680 addition measured after 30 mins by HTRF assay	ki	0.0004	uM
2-amino-N-[[6-(cyclopentyloxymethyl)-2-pyridinyl]methyl]-8-methoxyquinazoline-4-carboxamide	1325764: Displacement of [3H]5-amino-7-[2- phenethyl]-2-(furan-2-yl)-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine from human adenosine A2A receptor expressed in HEK293 cell membranes measured after 1 hr by TopCount scintillation counting method	ki	0.0005	uM
2-amino-8-methoxy-N-[(6-methyl-2-pyridinyl)methyl]quinazoline-4-carboxamide	1325764: Displacement of [3H]5-amino-7-[2- phenethyl]-2-(furan-2-yl)-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine from human adenosine A2A receptor expressed in HEK293 cell membranes measured after 1 hr by TopCount scintillation counting method	ki	0.0005	uM
2-amino-8-fluoro-N-(quinolin-8-ylmethyl)quinazoline-4-carboxamide	1277493: Displacement of [3H]SCH-58261 from human adenosine A2A receptor expressed in HEK cell membranes after 60 mins by microplate scintillation counting analysis	ki	0.0005	uM
5-[5-amino-2-[(R)-(3-fluoro-2-pyridinyl)-hydroxymethyl]-7-phenyl-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl]-1-methylpyridin-2-one	1782625: Antagonist activity at human A2aR expressed in CHO-K1 cells assessed as inhibition of cAMP accumulation preincubated for 30 mins followed by adenosine addition and measured for 30 mins by HTRF assay	ic50	0.0005	uM
4-[2-[7-amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]ethyl]-N,N-bis(2-chloroethyl)benzenesulfonamide	34373: Displacement of specific [3H]-SCH- 58261 binding at human Adenosine A2A receptor expressed in HEK293 cells.	ki	0.0006	uM

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Caffeine	increases response to substance, decreases activity, decreases expression, decreases reaction, affects response to substance	9
ZM 241385	affects binding, decreases activity	3
Lipopolysaccharides	increases expression, increases reaction, affects response to substance, affects cotreatment	3
titanium dioxide	decreases expression, increases expression	2
nickel sulfate	increases expression	2
zinc sulfide	affects cotreatment, increases expression, decreases expression	2
2-(4-(2-carboxyethyl)phenethylamino)-5’-N-ethylcarboxamidoadenosine	affects binding, increases activity, decreases expression, decreases reaction	2
Resveratrol	increases expression, increases reaction, affects cotreatment, decreases expression	2
Adenosine	decreases activity, increases expression, increases reaction, affects binding	2
Cisplatin	decreases expression, increases reaction, increases expression	2
Tretinoin	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
methotrexate polyglutamate	affects abundance, affects cotreatment	1
beta-lapachone	decreases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
chloroquine diphosphate	decreases expression	1
ochratoxin A	increases acetylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
2,2’-azobis(2-amidinopropane)	increases expression, increases phosphorylation, decreases response to substance, increases cleavage, decreases expression (+1 more)	1
1,3-dipropyl-8-cyclopentylxanthine	affects binding, decreases reaction	1
cadmium selenide	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1

ChEMBL screening assays

1679 unique, capped per target: 1372 binding, 301 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3707567	Binding	Binding Assay: The affinities of selected Purine Derivatives for the adenosine A1 receptor were determined by measuring the displacement of specific [3H] 2-chloro-N6-cyclopentyl adenosine binding in CHO cells stably transfected with human r	Purine derivatives as adenosine A1 receptor agonists and methods of use thereof
CHEMBL639497	Functional	Maximum increase in coronary flow, percent of control, and nucleoside concentration in coronary plasma at 12 uM	Dog coronary artery adenosine receptor: structure of the N6-aryl subregion. — J Med Chem
CHEMBL3863977	ADMET	Antagonist activity at adenosine A2a receptor (unknown origin)	Biphenyl Pyridazinone Derivatives as Inhaled PDE4 Inhibitors: Structural Biology and Structure-Activity Relationships. — J Med Chem

Cellosaurus cell lines

15 cell lines: 9 cancer cell line, 3 transformed cell line, 3 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8AZ	Abcam HCT 116 ADORA2A KO	Cancer cell line	Male
CVCL_B9D1	Abcam A-549 ADORA2A KO	Cancer cell line	Male
CVCL_B9VD	Abcam HeLa ADORA2A KO	Cancer cell line	Female
CVCL_C0S1	ACTOne ADORA2A	Transformed cell line	Female
CVCL_D2DS	Abcam MCF-7 ADORA2A KO	Cancer cell line	Female
CVCL_D7BA	Abeomics CHO-K1 A2AR	Spontaneously immortalized cell line	Female
CVCL_D7JM	Ubigene A-549 ADORA2A KO	Cancer cell line	Male
CVCL_D8H7	Ubigene HCT 116 ADORA2A KO	Cancer cell line	Male
CVCL_D8YT	Ubigene HEK293 ADORA2A KO	Transformed cell line	Female
CVCL_H384	CHO-K1/ADORA2A/Galpha15	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine