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ADORA2B

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Summary

ADORA2B (adenosine A2b receptor, HGNC:264) is a protein-coding gene on chromosome 17p12, encoding Adenosine receptor A2b (P29275). Receptor for adenosine.

This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17.

Source: NCBI Gene 136 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 82 total — 10 pathogenic
  • Druggable target: yes — 30 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000676

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:264
Approved symbolADORA2B
Nameadenosine A2b receptor
Location17p12
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000170425
Ensembl biotypeprotein_coding
OMIM600446
Entrez136

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000304222, ENST00000582124

RefSeq mRNA: 1 — MANE Select: NM_000676 NM_000676

CCDS: CCDS11173

Canonical transcript exons

ENST00000304222 — 2 exons

ExonStartEnd
ENSE000011236811597467915975746
ENSE000011236891594513015945583

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 87.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0383 / max 136.5660, expressed in 1481 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1596723.61321200
1596713.42511152

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499187.84gold quality
bronchial epithelial cellCL:000232887.76gold quality
pigmented layer of retinaUBERON:000178287.00gold quality
colonic mucosaUBERON:000031786.95gold quality
mucosa of sigmoid colonUBERON:000499385.86gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099185.48gold quality
epithelium of bronchusUBERON:000203185.36gold quality
bronchusUBERON:000218584.41gold quality
olfactory segment of nasal mucosaUBERON:000538682.94gold quality
mucosa of paranasal sinusUBERON:000503081.68gold quality
nasal cavity epitheliumUBERON:000538481.42gold quality
upper leg skinUBERON:000426281.08gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047380.98gold quality
ileal mucosaUBERON:000033179.79silver quality
lower esophagus mucosaUBERON:003583479.64gold quality
esophagus mucosaUBERON:000246978.64gold quality
skin of abdomenUBERON:000141677.66gold quality
transverse colonUBERON:000115777.49gold quality
rectumUBERON:000105277.47gold quality
mammalian vulvaUBERON:000099777.29gold quality
skin of hipUBERON:000155476.77gold quality
zone of skinUBERON:000001475.97gold quality
skin of legUBERON:000151175.91gold quality
cingulate cortexUBERON:000302775.49gold quality
nasal cavity mucosaUBERON:000182675.39gold quality
anterior cingulate cortexUBERON:000983575.34gold quality
right frontal lobeUBERON:000281075.24gold quality
monocyteCL:000057674.56gold quality
large intestineUBERON:000005974.35gold quality
mononuclear cellCL:000084274.18gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes6.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA2, HIF1A

miRNA regulators (miRDB)

30 targeting ADORA2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-477599.9875.006394
HSA-MIR-1213699.9872.815713
HSA-MIR-548E-5P99.8972.734486
HSA-MIR-221-5P99.8665.451052
HSA-MIR-807399.8665.211118
HSA-MIR-3680-3P99.7572.513095
HSA-MIR-64699.6867.841645
HSA-MIR-545-5P99.6670.182308
HSA-MIR-888-3P99.5369.771057
HSA-MIR-942-5P99.4168.401977
HSA-MIR-642A-3P99.2367.671258
HSA-MIR-642B-3P99.2367.671258
HSA-MIR-196A-3P99.1967.341204
HSA-MIR-129498.9169.261030
HSA-MIR-998698.9169.281024
HSA-MIR-4520-3P98.7566.55963
HSA-MIR-475298.7168.04833
HSA-MIR-6852-3P98.5467.601468
HSA-MIR-58198.3967.42835
HSA-MIR-7113-5P97.8867.331735
HSA-MIR-10397-3P97.7865.70601
HSA-MIR-390997.5566.78887
HSA-MIR-6836-3P97.0864.99712
HSA-MIR-569497.0667.70682
HSA-MIR-6730-3P97.0367.54889
HSA-MIR-3152-5P96.9866.88819

Literature-anchored findings (GeneRIF, showing 40)

  • 1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists (PMID:11906291)
  • A2BR binds to E3KARP and Ezrin upon agonist stimulation. (PMID:12080047)
  • Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. (PMID:12600879)
  • Selectively up-regulated by hypoxia (>5-fold increase in mRNA), and antagonists neutralize ATP-mediated endothelial permeability (PMID:12939345)
  • demonstrated induction of IgE synthesis by the interaction between adenosine-stimulated mast cells and B lymphocytes involves up-regulation of IL-4 and IL-13 mediated by A(2B) receptors (PMID:15187156)
  • Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and inhibits the expression of adenylate cyclase (PMID:15550390)
  • adenosine A2B receptors mediate the adenosine-induced contraction vasomotor effect in human chorionic vessels and that this involves synthesis of a thromboxane receptor activator or a related prostanoid. (PMID:15637124)
  • The PKC delta and epsilon isoforms are also involved in adenosine receptor A(2b) dependent upregulation of IL-6 expression. (PMID:15769552)
  • A(2B) receptors may play role in regulating glomerular remodeling associated with glomerular mesangial cell proliferation. Activation of A(2B) receptors may prevent glomerular remodeling associated with renal disease, hypertension, and diabetes. (PMID:16103269)
  • A2bR signals through adenylate cyclase (AC) 6 isoform in intestinal epithelial cells (PMID:16631311)
  • A(2B) receptors up-regulate IL-4 through G(q) signaling that is potentiated via cross-talk with G(s)-coupled pathways. (PMID:16707627)
  • Data indicate that adenosine increases the release of IL-19 from bronchial epithelial cells via activation of adenosine A(2B) receptors, and IL-19 in turn activates human monocytes to release TNF-alpha, which upregulates A(2B) receptor expression. (PMID:16778150)
  • Transcriptional coordination of adenosine a2B receptor by HIF-1alpha and amplified adenosine signaling during hypoxia. (PMID:17077301)
  • adenosine treatment of dermal papilla cells upregulates FGF-7 expression via the A2b adenosine receptor and that cAMP acts as one of the second messengers in this pathway (PMID:17301835)
  • Adenosine is not a direct GHSR agonist. In human embryonic kidney 293s (HEK) cells expressing GHSR, adenosine activates endogenously expressed A(2B)R resulting in calcium mobilization. (PMID:17428235)
  • Epac1 activation in HUVEC results in ERK1/2 activation, and this protein, at least in part, mediates response to the physiologically relevant event of A(2B)AR stimulation (PMID:17565009)
  • Short-term TNF-alpha cell treatment caused A(2B) AR phosphorylation inducing, in turn, impairment in A(2B) AR-G protein coupling and cAMP production (PMID:18004767)
  • Pharmacologic and genetic evidence for vascular A2BAR signaling as central control point of hypoxia-associated vascular leak. (PMID:18056839)
  • The results herein provide initial evidence that the inhibitory effect of hypoxia on MMP-9 by mature dendritic cells requires the activation of A(2b) in a cAMP/PKA-dependent pathway. (PMID:18215420)
  • our findings revealed the role of adenosine receptors in breast cancer cell lines on growth modulation role of A3 and functional form of A2B, although its involvement in cell growth modulation was not seen (PMID:18351132)
  • A(2B)-R are required for ASL volume homeostasis in human airways, and therapies directed at inhibiting A(2B)-R may lead to a cystic fibrosis-like phenotype with depleted ASL volume and mucus stasis. (PMID:18367727)
  • A2B adenosine receptors may differentially modulate hENTs in hPMEC, which could be a mechanism attempting to re-establish physiological extracellular adenosine levels in pre-eclampsia. (PMID:18703227)
  • Data suggest that adenosine receptor modulation may be useful for refining the use of chemotherapeutic drugs to treat human cancer more effectively. (PMID:19794965)
  • Hypoxic mature dendritic cells predominantly express adenosine receptor A2b. (PMID:19841638)
  • Studies indicate that adenosine mediates its actions by means of activation of specifiic G protein-coupled receptors, for which 4 subbtypes: A1R, A2AR, A2BR and A3R have (PMID:19883624)
  • Oxidative/nitrosative stress selectively altered A(2B) adenosine receptors in chronic obstructive pulmonary disease. (PMID:20008542)
  • Development of Chlamydia trachomatis is reversibly retarded by prolonged exposure of infected cells to extracellular adenosine mediated by the A2b adenosine receptor. (PMID:20011598)
  • demonstrated that hypoxia-induced apoptosis of T cells was mediated by A(2a )and A(2b) receptors. (PMID:20029460)
  • TNF-alpha-induced A(2B)AR expression in colonic epithelial cells is post-transcriptionally regulated by miR27b and miR128a (PMID:20388705)
  • ADORA2B was overexpressed in colorectal carcinomas grown under a hypoxic state, presumably promoting cancer cell growth. (PMID:20619442)
  • Adenosine A2A receptor is involved in cell surface expression of A2B receptor (PMID:20926384)
  • The results of this study suggest that deterioration of structure in the extracellular domains of GPCRs compromises overall receptor structure with profound consequences for receptor activation and constitutive activity. (PMID:21030693)
  • Adenosine A(B) receptors mediate an early induction of NR4A1 and a decrease in cell proliferation via the cAMP/Epac pathway in coronary artery smooth muscle cells. (PMID:21109603)
  • The ability of transgenic A2BR blockade to reduce circulating interleukin (IL)-6 levels by 24 hr may be explained by the reduction of bacterial load, and reflects that transgenic mice are going to live. (PMID:21242513)
  • [review] There is evidence that the ADORA2B receptor has cardioprotective effects upon its activation. However, controversy remains regarding the precise timing of activation required to induce cardioprotection. (PMID:21335481)
  • The main differences between the general dynamic behaviors of the A(2A)AR receptors and A(2B)AR receptors explored can be explained in terms of their particular sequences, loops lengths, and disulfide bridges. (PMID:21480628)
  • Inhibition of human mast cell activation would be a mechanism for A AR antagonists, but not A(2B) AR antagonists. (PMID:21506953)
  • Adenosine receptor expression and activation during the differentiation of mesenchymal stem cell to osteoblasts and adipocytes, was investigated. (PMID:21590734)
  • Only the disulfide bond of the adenosine A2B receptor is essential for ligand binding and receptor activation. (PMID:21620804)
  • 2’,3’-cAMP inhibits proliferation of vascular smooth muscle cells from the aorta and coronary arteries. This effect is due in part to metabolism of 2’,3’-cAMP to adenosine, with engagement of the A2B receptor. (PMID:21622827)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioadora2bENSDARG00000002533
mus_musculusAdora2bENSMUSG00000018500
rattus_norvegicusAdora2bENSRNOG00000002922
drosophila_melanogasterAdoRFBGN0039747

Paralogs (3): ADORA2A (ENSG00000128271), ADORA1 (ENSG00000163485), ADORA3 (ENSG00000282608)

Protein

Protein identifiers

Adenosine receptor A2b — P29275 (reviewed: P29275)

All UniProt accessions (1): P29275

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.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_000667* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR001435Adeno_A2B_rcptFamily
IPR001634Adenosn_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (43 total): helix 15, topological domain 8, transmembrane region 7, binding site 4, turn 4, glycosylation site 2, chain 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
8HDOELECTRON MICROSCOPY2.87
7XY6ELECTRON MICROSCOPY2.99
8HDPELECTRON MICROSCOPY3.2
7XY7ELECTRON MICROSCOPY3.26

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P29275-F188.560.71

Antibody-complex structures (SAbDab): 2 — 8HDO, 8HDP

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): 174; 254; 279; 280

Post-translational modifications (1): 311

Disulfide bonds (1): 78–171

Glycosylation sites (2): 153, 163

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

IDPathway
R-HSA-417973Adenosine P1 receptors
R-HSA-418555G alpha (s) signalling events
R-HSA-5683826Surfactant metabolism
R-HSA-9660821ADORA2B mediated anti-inflammatory cytokines production
R-HSA-162582Signal Transduction
R-HSA-1643685Disease
R-HSA-372790Signaling by GPCR
R-HSA-373076Class A/1 (Rhodopsin-like receptors)
R-HSA-388396GPCR downstream signalling
R-HSA-392499Metabolism of proteins
R-HSA-418038Nucleotide-like (purinergic) receptors
R-HSA-500792GPCR ligand binding
R-HSA-5663205Infectious disease
R-HSA-9658195Leishmania infection
R-HSA-9662851Anti-inflammatory response favouring Leishmania parasite infection
R-HSA-9664433Leishmania parasite growth and survival
R-HSA-9824443Parasitic Infection Pathways

MSigDB gene sets: 332 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, chr17p12, GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, TSENG_IRS1_TARGETS_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (16): positive regulation of chronic inflammatory response to non-antigenic stimulus (GO:0002882), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), activation of adenylate cyclase activity (GO:0007190), positive regulation of vascular endothelial growth factor production (GO:0010575), obsolete positive regulation of cGMP-mediated signaling (GO:0010753), obsolete cGMP-mediated signaling (GO:0019934), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-6 production (GO:0032755), vasodilation (GO:0042311), mast cell degranulation (GO:0043303), positive regulation of mast cell degranulation (GO:0043306), relaxation of vascular associated smooth muscle (GO:0060087), presynaptic modulation of chemical synaptic transmission (GO:0099171), G protein-coupled adenosine receptor signaling pathway (GO:0001973), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled adenosine receptor activity (GO:0001609), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-13 pathways:

CategoryPathways
Signaling by GPCR2
Nucleotide-like (purinergic) receptors1
GPCR downstream signalling1
Metabolism of proteins1
Anti-inflammatory response favouring Leishmania parasite infection1
Signal Transduction1
GPCR ligand binding1
Class A/1 (Rhodopsin-like receptors)1
Disease1
Parasitic Infection Pathways1
Leishmania parasite growth and survival1
Leishmania infection1
Infectious disease1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
positive regulation of cytokine production3
synapse3
G protein-coupled receptor activity2
cellular anatomical structure2
chronic inflammatory response to non-antigenic stimulus1
positive regulation of chronic inflammatory response1
regulation of chronic inflammatory response to non-antigenic stimulus1
signal transduction1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway1
adenylate cyclase activator activity1
positive regulation of adenylate cyclase activity1
vascular endothelial growth factor production1
regulation of vascular endothelial growth factor production1
chemokine production1
regulation of chemokine production1
interleukin-6 production1
regulation of interleukin-6 production1
blood vessel diameter maintenance1
mast cell activation involved in immune response1
mast cell mediated immunity1
lysosome localization1
leukocyte degranulation1
establishment of organelle localization1
positive regulation of leukocyte degranulation1
mast cell degranulation1
regulation of mast cell degranulation1
vasodilation1
relaxation of smooth muscle1
negative regulation of smooth muscle contraction1
modulation of chemical synaptic transmission1
presynapse1
G protein-coupled purinergic receptor signaling pathway1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
G protein-coupled adenosine receptor signaling pathway1
transmembrane signaling receptor activity1
G protein-coupled receptor signaling pathway1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ADORA2BNTN1O95631797
ADORA2BENTPD1P49961752
ADORA2BNT5EP21589715
ADORA2BUNC5BQ8IZJ1624
ADORA2BALOX12P18054609
ADORA2BNEO1Q92859592
ADORA2BADAP00813555
ADORA2BNTN4Q9HB63552
ADORA2BDCCP43146549
ADORA2BLTBP3Q9NS15518
ADORA2BDSCAMO60469515
ADORA2BPER1O15534505
ADORA2BLTBP2Q14767502
ADORA2BLTBP1P22064498
ADORA2BAKT1P31749492

IntAct

15 interactions, top by confidence:

ABTypeScore
ADORA2AADORA2Bpsi-mi:“MI:2364”(proximity)0.540
ADORA2AADORA2Bpsi-mi:“MI:0915”(physical association)0.540
ADORA2BRAMP1psi-mi:“MI:0915”(physical association)0.400
RAMP1ADORA2Bpsi-mi:“MI:0915”(physical association)0.400
ADORA2BRAMP2psi-mi:“MI:0915”(physical association)0.400
RAMP3ADORA2Bpsi-mi:“MI:0915”(physical association)0.400
ADORA2BTPD52L2psi-mi:“MI:0915”(physical association)0.370
ADORA2BZNF267psi-mi:“MI:0915”(physical association)0.370
ADORA2BSCAMP2psi-mi:“MI:0914”(association)0.350

BioGRID (39): ADORA2B (Affinity Capture-Western), ADORA2B (Affinity Capture-Western), ADORA2B (Affinity Capture-RNA), WFS1 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), SURF4 (Affinity Capture-MS), TSPAN15 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), FAM134C (Affinity Capture-MS), SLC5A3 (Affinity Capture-MS), REEP5 (Affinity Capture-MS), SDC4 (Affinity Capture-MS), GTF2IRD1 (Affinity Capture-MS)

ESM2 similar proteins: C3ZQF9, E7F7V7, F1R332, O02664, O08892, O13076, O35214, O70431, O77621, P11614, P17124, P25021, P25102, P28221, P28222, P28334, P28564, P28565, P29275, P29276, P35404, P35406, P46636, P47747, P47800, P49144, P49145, P56496, P60020, P60021, P61752, P79211, P79250, P79400, P79748, Q0EAB5, Q1LZD0, Q29003, Q32ZE2, Q588Y6

Diamond homologs: O02213, O02662, O02667, O13076, O70528, O77621, P04761, P08483, P08908, P08909, P08911, P08912, P0DMS8, P11229, P11483, P11616, P11617, P12657, P15823, P16395, P17124, P18841, P19327, P20309, P22270, P25021, P25099, P25102, P25962, P28190, P28285, P28286, P28335, P28647, P29274, P29275, P29276, P30542, P30543, P34968

SIGNOR signaling

10 interactions.

AEffectBMechanism
ADORA2B“up-regulates activity”GNASbinding
ADORA2B“up-regulates activity”GNALbinding
ADORA2B“up-regulates activity”GNAI1binding
ADORA2B“up-regulates activity”GNAI3binding
ADORA2B“up-regulates activity”GNAO1binding
ADORA2B“up-regulates activity”GNAZbinding
ADORA2B“up-regulates activity”GNAQbinding
ADORA2B“up-regulates activity”GNA14binding
adenosine“up-regulates activity”ADORA2B“chemical activation”
adenosine“up-regulates activity”ADORA2Bbinding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic10
Likely pathogenic0
Uncertain significance65
Likely benign1
Benign4

Top pathogenic / likely-pathogenic (10)

Variant IDHGVSClassification
148088GRCh38/hg38 17p12-11.2(chr17:15210400-18280816)x3Pathogenic
148716GRCh38/hg38 17p12(chr17:14671118-15952996)x1Pathogenic
150382GRCh38/hg38 17p12(chr17:15190283-15952996)x3Pathogenic
154979GRCh38/hg38 17p12-11.2(chr17:15066799-17472457)x1Pathogenic
253611GRCh37/hg19 17p12-11.2(chr17:15767020-20261250)x3Pathogenic
2685597GRCh37/hg19 17p12-11.2(chr17:15694772-20582794)x1Pathogenic
3063517GRCh37/hg19 17p12-11.2(chr17:15759103-20564268)x1Pathogenic
394560GRCh37/hg19 17p12-11.2(chr17:15745315-20261191)x1Pathogenic
58107GRCh38/hg38 17p12-11.2(chr17:15259164-20925299)x3Pathogenic
58693GRCh38/hg38 17p12-11.2(chr17:10892259-17964282)x3Pathogenic

SpliceAI

623 predictions. Top by Δscore:

VariantEffectΔscore
17:15945579:CTCAG:Cdonor_loss0.9900
17:15945580:TCAGG:Tdonor_loss0.9900
17:15945581:CAGGT:Cdonor_loss0.9900
17:15945582:AGGT:Adonor_loss0.9900
17:15945583:GG:Gdonor_loss0.9900
17:15945584:GTGA:Gdonor_loss0.9900
17:15945585:T:Adonor_loss0.9900
17:15966985:A:Tdonor_gain0.9900
17:15974676:CAGG:Cacceptor_loss0.9900
17:15974677:A:Tacceptor_loss0.9900
17:15974678:G:Tacceptor_loss0.9900
17:15966984:G:GTdonor_gain0.9800
17:15974674:A:Gacceptor_gain0.9800
17:15974677:A:AGacceptor_gain0.9800
17:15974678:G:GGacceptor_gain0.9800
17:15974678:GGT:Gacceptor_gain0.9800
17:15946464:A:Tdonor_gain0.9500
17:15964130:G:GAdonor_gain0.9500
17:15974678:GGTAT:Gacceptor_gain0.9500
17:15946461:TTGA:Tdonor_gain0.9400
17:15964178:A:AGdonor_gain0.9400
17:15947383:G:GTdonor_gain0.9300
17:15946456:G:GGdonor_gain0.9200
17:15964178:A:Gdonor_gain0.9200
17:15950314:G:GTdonor_gain0.9100
17:15964129:T:TAdonor_gain0.9100
17:15974673:A:AGacceptor_gain0.9100
17:15964182:G:GGdonor_gain0.9000
17:15966963:G:GTdonor_gain0.9000
17:15969088:G:GTdonor_gain0.9000

AlphaMissense

2153 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:15945405:G:CD53H0.999
17:15945406:A:CD53A0.999
17:15945406:A:TD53V0.999
17:15975070:T:CF243L0.999
17:15975072:T:AF243L0.999
17:15975072:T:GF243L0.999
17:15945323:C:AN25K0.998
17:15945323:C:GN25K0.998
17:15945406:A:GD53G0.998
17:15945407:C:AD53E0.998
17:15945407:C:GD53E0.998
17:15945417:G:AG57R0.998
17:15945417:G:CG57R0.998
17:15945418:G:AG57E0.998
17:15945531:A:CS95R0.998
17:15945533:C:AS95R0.998
17:15945533:C:GS95R0.998
17:15974731:T:AW130R0.998
17:15974731:T:CW130R0.998
17:15974861:T:GF173C0.998
17:15975201:T:AN286K0.998
17:15975201:T:GN286K0.998
17:15945318:G:CG24R0.997
17:15945405:G:TD53Y0.997
17:15945417:G:TG57W0.997
17:15974860:T:CF173L0.997
17:15974862:T:AF173L0.997
17:15974862:T:GF173L0.997
17:15975079:T:CC246R0.997
17:15975082:T:AW247R0.997

dbSNP variants (sampled 300 via entrez): RS1000032711 (17:15970611 T>C), RS1000050478 (17:15882680 T>C), RS1000053698 (17:15961559 G>C), RS1000083595 (17:15897133 A>T), RS1000120892 (17:15897911 A>T), RS1000193074 (17:15965348 T>C), RS1000211730 (17:15876982 C>A), RS1000222288 (17:15849618 G>A), RS1000276378 (17:15939916 A>T), RS1000279425 (17:15858309 G>A), RS1000283804 (17:15880359 G>A), RS1000287393 (17:15891338 C>T), RS1000296257 (17:15931465 A>G), RS1000337240 (17:15970881 C>T), RS1000354513 (17:15970600 C>G)

Disease associations

OMIM: gene MIM:600446 | disease phenotypes: MIM:162500

GenCC curated gene-disease

Mondo (2): hereditary neuropathy with liability to pressure palsies (MONDO:0008087), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (1): Hereditary neuropathy with liability to pressure palsies (Orphanet:640)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST001537_5Immune reponse to smallpox (secreted IL-12p40)3.000000e-07
GCST011743_26HDL cholesterol levels in HIV infection3.000000e-06

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004645response to vaccine
EFO:0004873cytokine measurement
EFO:0004612high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

DescriptorNameTree numbers
D018270Carcinoma, Ductal, BreastC04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
C536965Tomaculous neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2094257 (PROTEIN FAMILY), CHEMBL2095234 (SELECTIVITY GROUP), CHEMBL2096679 (SELECTIVITY GROUP), CHEMBL2096908 (SELECTIVITY GROUP), CHEMBL2111329 (PROTEIN FAMILY), CHEMBL255 (SINGLE PROTEIN), CHEMBL4296621 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 462,815 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL113CAFFEINE4200,591
CHEMBL1355736THEOPHYLLINE4752
CHEMBL477ADENOSINE4222,014
CHEMBL317052REGADENOSON ANHYDROUS4186
CHEMBL431770ISTRADEFYLLINE41,769
CHEMBL628PENTOXIFYLLINE426,061
CHEMBL70246ACEFYLLINE41,359
CHEMBL1950554BINODENOSON3206
CHEMBL3545407TRABODENOSON3142
CHEMBL52333ROLOFYLLINE3421
CHEMBL2105747TOZADENANT3742
CHEMBL414157TONAPOFYLLINE3216
CHEMBL277465DENBUFYLLINE22,034
CHEMBL279898ENPROFYLLINE21,955
CHEMBL1950553SONEDENOSON276
CHEMBL392149TECADENOSON2382
CHEMBL3987016MIVEBRESIB2773
CHEMBL4297184CIFORADENANT21,478
CHEMBL447664VIPADENANT2679
CHEMBL4594442IMARADENANT2979
CHEMBL4740383ETRUMADENANT2
CHEMBL592435DERENOFYLLINE2
CHEMBL65547PSILOCIN2
CHEMBL699ETOFYLLINE2
CHEMBL1672627LAS1010571
CHEMBL186113GW-3282671
CHEMBL197669ST15351
CHEMBL260933GS 62011
CHEMBL3694769PBF-5091
CHEMBL440115FK4531

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adenosine receptors

Most potent curated ligand interactions (85 total), top 25:

LigandActionAffinityParameter
[3H]MRS1754Antagonist9.8pKd
[3H]OSIP339391Antagonist9.8pKd
[3H]PSB603Antagonist9.4pKd
PSB-0788Antagonist9.4pKi
OSIP339391Antagonist9.3pKi
PSB603Antagonist9.26pKi
MRS1706Antagonist8.86pKi
MRS1754Antagonist8.8pKi
PSB-12105Antagonist8.7pKi
ATL802Antagonist8.63pKi
BAY 60-6583Agonist8.52pKi
MRE 2029F20Antagonist8.5pKi
ISAM-140Antagonist8.46pKi
AS99Antagonist8.4pKi
AS101Antagonist8.4pKi
AS100Antagonist8.2pKi
ZM-241385Antagonist8.2pKi
AS70Antagonist8.1pKi
AS96Antagonist8.0pKi
xanthine amine congenerAntagonist7.9pA2
DEPXAntagonist7.9pKi
[3H]ZM 241385Antagonist7.9pKd
CGS 15943Antagonist7.8pA2
AS94Antagonist7.8pKi
LAS38096Antagonist7.77pKi

Binding affinities (BindingDB)

192 measured of 246 human assays (259 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
[4-[2-amino-3,5-dicyano-6-[[2-(methylcarbamoyl)-4-pyridinyl]methylsulfanyl]-4-pyridinyl]phenyl] N,N-dimethylsulfamateEC500.04 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-4-[4-(2-aminoethoxy)phenyl]-3,5-dicyano-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.04 nMUS-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-carboxamideEC500.06 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]-N-cyclopropylpyridine-2-carboxamideEC500.08 nMUS-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-carboxamideEC500.1 nMUS-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-carboxamideEC500.1 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(4-methoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(4-ethoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(3,5-difluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-(3-hydroxyazetidin-1-yl)-4-phenyl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-[2-hydroxyethyl(methyl)amino]-4-phenyl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.2 nMUS-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-carboxamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-[[(2S)-2,3-dihydroxypropyl]amino]-4-phenyl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.2 nMUS-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-methylbenzamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]-N-(2-aminoethyl)benzamideEC500.2 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-[4-(3-Cyanophenyl)-5-(4-methoxyquinazolin-6-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamideKI0.2 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-pyrazolo[1,5-a]pyridin-5-yl-thiazol-2-yl]morpholine-4-carboxamideKI0.2 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
4-[[6-amino-3,5-dicyano-4-(4-fluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(3,4-difluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(4-fluoro-3-methoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]benzamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(3-propoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[1-[[6-amino-3,5-dicyano-4-[4-(2-hydroxyethoxy)phenyl]-2-pyridinyl]sulfanyl]ethyl]-N-methylbenzamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[[3,5-dicyano-4-[4-(2-hydroxyethoxy)phenyl]-6-pyrrolidin-1-yl-2-pyridinyl]sulfanylmethyl]-N-ethylbenzamideEC500.3 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-[4-(3-Cyanophenyl)-5-(3-methylbenzimidazol-5-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamideKI0.3 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-imidazo[1,2-a]pyridin-6-yl-thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamideKI0.3 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amineKI0.35 nM
4-[[6-amino-3,5-dicyano-4-[4-(methylamino)phenyl]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-4-[4-(2-hydroxyethoxy)phenyl]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[(3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-(2,4-dimethoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-4-[4-[2-[[(2S)-2-aminopropanoyl]amino]ethoxy]phenyl]-3,5-dicyano-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[1-[[6-amino-3,5-dicyano-4-[4-(2-hydroxyethoxy)phenyl]-2-pyridinyl]sulfanyl]ethyl]benzamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[(6-amino-3,5-dicyano-4-phenyl-2-pyridinyl)oxymethyl]-N-cyclopropylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-(2-hydroxyethylamino)-4-(4-methoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[[6-amino-3,5-dicyano-4-(4-fluorophenyl)-2-pyridinyl]sulfanylmethyl]-N-[(2R)-2,3-dihydroxypropyl]benzamideEC500.4 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-[4-(3-Cyanophenyl)-5-(4-methyl-6-quinolyl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamideKI0.4 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-(3-methylimidazo[1,2-a]pyridin-6-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamideKI0.4 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
4-[[6-amino-3,5-dicyano-4-[3-(2-hydroxyethoxy)phenyl]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.5 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-[3-[[6-amino-3,5-dicyano-4-(3,4-difluorophenyl)-2-pyridinyl]sulfanylmethyl]phenyl]methanesulfonamideEC500.5 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[6-amino-3,5-dicyano-4-[4-fluoro-3-(trifluoromethyl)phenyl]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.5 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-(3-hydroxyazetidin-1-yl)-4-(4-methoxyphenyl)-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.5 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-cyclopropyl-4-[(3,5-dicyano-4-phenyl-6-pyrrolidin-1-yl-2-pyridinyl)sulfanylmethyl]pyridine-2-carboxamideEC500.5 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-[4-(3-Cyanophenyl)-5-(7-methyl-1H-indazol-5-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamideKI0.5 nMUS-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
4-[[3,5-dicyano-4-phenyl-6-[(3,3,3-trifluoro-2-hydroxypropyl)amino]-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.6 nMUS-9187428: Substituted dicyanopyridines and use thereof
N-[3-[[6-amino-3,5-dicyano-4-(4-fluorophenyl)-2-pyridinyl]sulfanylmethyl]phenyl]methanesulfonamideEC500.7 nMUS-9187428: Substituted dicyanopyridines and use thereof
4-[[3,5-dicyano-6-(2-hydroxyethylamino)-4-pyridin-2-yl-2-pyridinyl]sulfanylmethyl]-N-methylpyridine-2-carboxamideEC500.7 nMUS-9187428: Substituted dicyanopyridines and use thereof
3-[(3,5-dicyano-4-phenyl-2-pyridinyl)sulfanylmethyl]benzoic acidEC500.8 nMUS-9187428: Substituted dicyanopyridines and use thereof
2-Cl-CPAKI0.83 nMUS-8470800: Method of reducing intraocular pressure in humans
4-[[6-amino-3,5-dicyano-4-(4-fluorophenyl)-2-pyridinyl]oxymethyl]-N-methylpyridine-2-carboxamideEC500.9 nMUS-9187428: Substituted dicyanopyridines and use thereof

ChEMBL bioactivities

4256 potent at pChembl≥5 of 4445 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.08Ki0.0835nMCHEMBL4552275
10.00IC500.1nMCHEMBL5827075
9.86Ki0.137nMCHEMBL4450864
9.83Ki0.148nMCHEMBL4464522
9.81Ki0.153nMCHEMBL4540206
9.80Ki0.159nMCHEMBL4454481
9.80Ki0.157nMCHEMBL486478
9.77Ki0.17nMCHEMBL3121728
9.77Kd0.17nMCHEMBL500634
9.72EC500.1905nMCHEMBL605668
9.67Ki0.215nMCHEMBL4463929
9.67Ki0.215nMCHEMBL483261
9.63Ki0.234nMCHEMBL4466625
9.61Ki0.244nMCHEMBL4567785
9.59EC500.257nMBINODENOSON
9.55Ki0.281nMCHEMBL519390
9.52Ki0.303nMCHEMBL486479
9.49EC500.3236nMCHEMBL5177040
9.49EC500.3236nMCHEMBL611607
9.47Ki0.342nMCHEMBL4460114
9.47IC500.34nMCHEMBL4643397
9.45Ki0.352nMCHEMBL4530074
9.42EC500.3802nMCHEMBL5177040
9.41Ki0.393nMCHEMBL482436
9.41EC500.389nMCHEMBL2311197
9.40Ki0.397nMCHEMBL4440526
9.40IC500.4nMCHEMBL5966778
9.40Ki0.4nMCHEMBL1289569
9.40Ki0.4nMCHEMBL485862
9.39Ki0.403nMCHEMBL4441276
9.39Ki0.406nMCHEMBL483487
9.39Ki0.41nMCHEMBL485862
9.39Kd0.403nMCHEMBL483688
9.38Ki0.421nMCHEMBL4454417
9.37Ki0.432nMCHEMBL4443090
9.36Ki0.44nMCHEMBL1289676
9.35EC500.4467nMCHEMBL2094089
9.35Ki0.446nMCHEMBL484900
9.33EC500.4677nMCHEMBL2113592
9.32Ki0.473nMCHEMBL4566170
9.32Ki0.473nMCHEMBL519253
9.30Ki0.5nMCHEMBL3786849
9.30Ki0.5nMCHEMBL485862
9.30EC500.5012nMCHEMBL605878
9.27IC500.534nMCHEMBL483688
9.26Ki0.553nMCHEMBL483688
9.22Ki0.595nMCHEMBL520830
9.22Ki0.6nMCHEMBL1672631
9.21Ki0.616nMCHEMBL4456096
9.21Ki0.61nMCHEMBL482638

PubChem BioAssay actives

2164 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.

CompoundAssayTypeValueUnit
8-[4-[4-(2-bromophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0001uM
8-[4-[4-[(3-bromophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0001uM
8-[4-[4-(4-bromophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0001uM
8-[4-[4-(4-iodophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0002uM
8-[4-[4-(4-chloro-3-methoxyphenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0002uM
8-[4-[4-(3-bromophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0002uM
8-[4-[4-[(4-bromophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0002uM
8-[4-[4-[(4-azidophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0002uM
8-cyclohexyl-1,3,7-trimethylpurine-2,6-dione30655: Binding affinity for adenosine A2 receptor using [3H]- NECA antagonism of adenylate cyclase activation in human plateletski0.0002uM
8-[4-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-ethyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0002uM
1-ethyl-8-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]sulfonylphenyl]-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0002uM
8-[4-[4-(3-chlorophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0003uM
4-[4-[2-[[7-amino-2-(furan-2-yl)-[1,3]thiazolo[5,4-d]pyrimidin-5-yl]amino]ethyl]piperazin-1-yl]benzenesulfonamide1667713: Inverse agonist activity at human A2B receptor expressed in CHO cells assessed as reduction in cAMP levelic500.0003uM
[2-amino-5-[4-[1-[6-[[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]hexyl]triazol-4-yl]phenyl]-4-[3-(trifluoromethyl)phenyl]thiophen-3-yl]-phenylmethanone1869547: Agonist activity at A2BR in human NHVCF cells assessed as cAMP accumulation incubated for 30 mins by LANCE cAMP assayec500.0003uM
1-propyl-8-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]sulfonylphenyl]-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0003uM
1-ethyl-8-[4-[4-[[3-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]sulfonylphenyl]-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0003uM
(2R,3R,4S,5R)-2-[6-[[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol30507: Coronary arteries vasodilation at the adenosine A2 receptor in langendorff guinea pig heart preparationec500.0004uM
8-[4-[4-[(3-methylphenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0004uM
8-[4-[4-(2-chlorophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0004uM
8-[4-[4-(2-methylphenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0004uM
8-[4-[4-(4-chloro-3-hydroxyphenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0004uM
8-[4-[4-(3-chloro-4-methoxyphenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0004uM
8-[4-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylphenyl]-1-ethyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0004uM
8-[4-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione372168: Binding affinity to human recombinant adenosine A2B receptor expressed in CHO cells by saturation experimentkd0.0004uM
8-[4-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0004uM
8-[4-[4-[(3-fluorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0004uM
N-[2-[[2-phenyl-8-[4-(3-phenylpropyl)piperazine-1-carbonyl]-7H-purin-6-yl]amino]ethyl]acetamide1289963: Displacement of [3H]OSIP339391 from human recombinant Adenosine A2B receptor expressed in HEK293 cells after 60 minski0.0005uM
8-[4-[4-[(4-bromo-3-fluorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0005uM
8-[4-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylphenyl]-1-prop-2-ynyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0005uM
8-[4-[4-(3-methoxyphenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0006uM
8-[4-[4-[(4-fluoro-3-methoxyphenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0006uM
8-[4-[4-(3-fluorophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0006uM
8-[4-[4-(4-fluorophenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0006uM
8-[4-(4-phenylpiperazin-1-yl)sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0006uM
8-[4-[4-[(3-chlorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-ethyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0006uM
8-[4-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0006uM
8-[4-[4-(4-methylphenyl)piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0007uM
4-(2,6-dioxo-1-propyl-3,7-dihydropurin-8-yl)benzenesulfonyl fluoride1851394: Displacement of [3H]PSB-603 from human adenosine A2B receptor expressed in CHO cell membrane preincubated for 4 hrs followed by [3H]PSB-603 addition and measured after 0.5 hrs by radioligand displacement assayki0.0007uM
8-(4-isothiocyanatophenyl)-1-propyl-3,7-dihydropurine-2,6-dione1851394: Displacement of [3H]PSB-603 from human adenosine A2B receptor expressed in CHO cell membrane preincubated for 4 hrs followed by [3H]PSB-603 addition and measured after 0.5 hrs by radioligand displacement assayki0.0007uM
3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid30506: Coronary arteries vasodilation at the Adenosine A2 receptor in langendorff guinea pig heart preparationec500.0007uM
1-ethyl-8-[4-[4-[(3-fluorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0007uM
2-[3-[5-(2-aminopropan-2-yl)-3-methyl-2-pyridinyl]cyclobutyl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine2128084: Antagonist activity at Adenosine A2b receptor (unknown origin)ic500.0008uM
2-[3-[5-(2-aminopropan-2-yl)-3-chloro-2-pyridinyl]cyclobutyl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine2128084: Antagonist activity at Adenosine A2b receptor (unknown origin)ic500.0008uM
7-methoxy-2-[2-(1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropyl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine2128084: Antagonist activity at Adenosine A2b receptor (unknown origin)ic500.0008uM
2-[6-[3-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)cyclobutyl]-3-pyridinyl]propan-2-ol2128084: Antagonist activity at Adenosine A2b receptor (unknown origin)ic500.0008uM
2-[3-[5-(2-aminopropan-2-yl)-2-pyridinyl]cyclopentyl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine2022018: Binding affinity to recombinant human adenosine A2B receptor expressed in HEK293 cell membrane incubated for 15 to 30 mins by Topcount scintillation counter assayic500.0008uM
7-methoxy-2-[2-(1-methylbenzimidazol-2-yl)cyclopropyl]-[1,2,4]triazolo[1,5-c]quinazolin-5-amine2128084: Antagonist activity at Adenosine A2b receptor (unknown origin)ic500.0008uM
8-[4-[4-[(3-chlorophenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0008uM
1-propyl-8-[4-[4-[[3-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]sulfonylphenyl]-3,7-dihydropurine-2,6-dione372151: Displacement of [3H]PSB-603 from human recombinant adenosine A2B receptor expressed in CHO cellski0.0008uM
8-[4-[4-[(3-fluoro-4-methoxyphenyl)methyl]piperazin-1-yl]sulfonylphenyl]-1-propyl-3,7-dihydropurine-2,6-dione1549328: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting methodki0.0009uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneincreases expression, increases methylation7
Valproic Acidaffects cotreatment, increases expression, increases methylation4
Estradioldecreases expression, increases reaction, increases expression, affects cotreatment3
Aflatoxin B1affects expression, increases expression3
bisphenol Adecreases methylation, affects cotreatment, decreases expression2
sodium arseniteincreases abundance, decreases expression2
entinostatincreases expression, affects cotreatment2
Cisplatinaffects response to substance, affects cotreatment, increases expression2
Lipopolysaccharidesdecreases expression, affects response to substance, increases expression, affects cotreatment2
Tobacco Smoke Pollutionincreases expression2
Cadmium Chloridedecreases expression2
tungsten carbideincreases expression, affects cotreatment1
triphenyl phosphateaffects expression1
butylphenincreases expression1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)affects expression, affects response to substance1
sulforaphaneincreases expression1
1,7-dimethylxanthinedecreases activity, decreases expression, decreases reaction1
zinc chromatedecreases expression, increases abundance1
nickel sulfateincreases expression1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxalineincreases expression1
S-(1,2-dichlorovinyl)cysteineincreases expression, affects cotreatment, decreases expression, affects response to substance1
isobutyl alcoholaffects cotreatment, decreases expression, increases abundance1
1,3-dipropyl-8-cyclopentylxanthineaffects binding1
chromium hexavalent iondecreases expression, increases abundance1
perfluorooctane sulfonic acidincreases expression1
seocalcitoldecreases expression1
CGP 52608increases reaction, affects binding1
ZM 241385affects binding1
K 7174increases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideincreases expression, affects cotreatment1

ChEMBL screening assays

907 unique, capped per target: 632 binding, 273 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3707567BindingBinding 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 rPurine derivatives as adenosine A1 receptor agonists and methods of use thereof
CHEMBL639497FunctionalMaximum increase in coronary flow, percent of control, and nucleoside concentration in coronary plasma at 12 uMDog coronary artery adenosine receptor: structure of the N6-aryl subregion. — J Med Chem
CHEMBL3863978ADMETAntagonist activity at adenosine A2b receptor (unknown origin)Biphenyl Pyridazinone Derivatives as Inhaled PDE4 Inhibitors: Structural Biology and Structure-Activity Relationships. — J Med Chem

Cellosaurus cell lines

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

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

CellosaurusNameCategorySex
CVCL_C0S2ACTOne ADORA2BTransformed cell lineFemale
CVCL_D7JNUbigene A-549 ADORA2B KOCancer cell lineMale
CVCL_D8YUUbigene HEK293 ADORA2B KOTransformed cell lineFemale
CVCL_H385CHO-K1/ADORA2B/Galpha15Spontaneously immortalized cell lineFemale
CVCL_KU74cAMP Hunter CHO-K1 ADORA2B GsSpontaneously immortalized cell lineFemale
CVCL_SB77HAP1 ADORA2B (-) 1Cancer cell lineMale
CVCL_SB78HAP1 ADORA2B (-) 2Cancer cell lineMale
CVCL_YJ98HEK293 ADORA2B HiTSeekerTransformed cell lineFemale
CVCL_ZK40GeneBLAzer ADORA2B-CRE-bla CHO-K1Spontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT03414970PHASE3ACTIVE_NOT_RECRUITINGHypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT01401257PHASE2COMPLETEDPhase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT00461344PHASE2TERMINATEDDocetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999PHASE2NOT_YET_RECRUITINGRandomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT05902351Not specifiedRECRUITINGNatural History Study for Charcot Marie Tooth Disease
NCT00637364PHASE1/PHASE2SUSPENDEDHigh Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855PHASE1/PHASE2COMPLETEDTalimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908EARLY_PHASE1COMPLETEDBroccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041EARLY_PHASE1COMPLETEDIntraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974Not specifiedACTIVE_NOT_RECRUITINGNipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198Not specifiedTERMINATEDOncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397Not specifiedUNKNOWNMRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532Not specifiedCOMPLETEDLiving Well After Breast Surgery

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot