P2RY1

Summary

P2RY1 (purinergic receptor P2Y1, HGNC:8539) is a protein-coding gene on chromosome 3q25.2, encoding P2Y purinoceptor 1 (P47900). Receptor for extracellular adenine nucleotides such as ADP.

The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor functions as a receptor for extracellular ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation.

Source: NCBI Gene 5028 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 24 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈4% of expected missense variation)
• GTEx eGene: eQTL in 16 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug; 3 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 1 — Diquafosol Tetrasodium
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.93 (unconstrained)
• MANE Select transcript: NM_002563
• Interaction hub: 1,738 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8539
Approved symbol	P2RY1
Name	purinergic receptor P2Y1
Location	3q25.2
Locus type	gene with protein product
Status	Approved
Aliases	P2Y1, SARCC
Ensembl gene	ENSG00000169860
Ensembl biotype	protein_coding
OMIM	601167
Entrez	5028

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000305097

ENST00000305097

RefSeq mRNA: 1 — MANE Select: NM_002563 NM_002563

CCDS: CCDS3169

Canonical transcript exons

ENST00000305097 — 1 exons

Exon	Start	End
ENSE00001131708	152835131	152841439

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.9176 / max 103.8680, expressed in 947 samples.

Highest expression (Bgee): gingival epithelium, esophagus squamous epithelium, gingiva, endothelial cell, oral cavity.

Genetic regulation across tissues (GTEx eQTL / sQTL)

P2RY1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	3.3e-45	+0.42	3:152617923:T:C
Brain Cerebellar Hemisphere	eqtl	9.2e-12	-0.45	3:152627445:G:A
Brain Cerebellum	eqtl	4.8e-07	+0.39	3:152612492:G:A
Artery Aorta	eqtl	1.8e-03	-0.28	3:152811382:T:C
Skin Not Sun Exposed Suprapubic	eqtl	6.2e-03	+0.17	3:152599937:C:T
Muscle Skeletal	eqtl	6.5e-03	-0.10	3:152547807:A:C
Cells EBV-transformed lymphocytes	eqtl	1.3e-02	-0.45	3:152329928:A:G
Whole Blood	eqtl	1.7e-02	+0.43	3:152659231:G:C
Lung	eqtl	1.7e-02	+0.46	3:153356411:C:T
Esophagus Mucosa	eqtl	2.0e-02	+0.41	3:153024758:T:C
Cells Cultured fibroblasts	eqtl	2.7e-02	-0.31	3:152851982:G:A
Brain Caudate basal ganglia	eqtl	2.9e-02	-0.14	3:152646057:T:C
Heart Atrial Appendage	eqtl	3.3e-02	+0.22	3:152631455:T:A
Esophagus Muscularis	eqtl	3.9e-02	+0.68	3:152491541:A:G
Heart Left Ventricle	eqtl	4.0e-02	-0.58	3:152332959:G:A
Brain Putamen basal ganglia	eqtl	4.7e-02	-0.61	3:152625015:C:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
39322	2.8756	779
39321	1.0954	503
39320	0.4610	211
39323	0.3404	188
39319	0.1451	68

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	98.05	gold quality
esophagus squamous epithelium	UBERON:0006920	97.92	gold quality
gingiva	UBERON:0001828	96.49	gold quality
endothelial cell	CL:0000115	93.66	gold quality
oral cavity	UBERON:0000167	90.17	gold quality
epithelium of esophagus	UBERON:0001976	89.89	gold quality
squamous epithelium	UBERON:0006914	88.09	gold quality
medial globus pallidus	UBERON:0002477	87.33	gold quality
visceral pleura	UBERON:0002401	86.04	gold quality
lower esophagus mucosa	UBERON:0035834	84.56	gold quality
esophagus mucosa	UBERON:0002469	84.10	gold quality
amniotic fluid	UBERON:0000173	83.74	gold quality
placenta	UBERON:0001987	83.05	gold quality
nucleus accumbens	UBERON:0001882	82.89	gold quality
globus pallidus	UBERON:0001875	82.82	gold quality
tibia	UBERON:0000979	82.28	gold quality
lower lobe of lung	UBERON:0008949	81.97	gold quality
colonic mucosa	UBERON:0000317	81.88	gold quality
tendon of biceps brachii	UBERON:0008188	81.47	silver quality
pharyngeal mucosa	UBERON:0000355	81.00	gold quality
secondary oocyte	CL:0000655	80.99	gold quality
germinal epithelium of ovary	UBERON:0001304	80.73	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.57	gold quality
right lung	UBERON:0002167	80.45	gold quality
vagina	UBERON:0000996	79.40	gold quality
sigmoid colon	UBERON:0001159	79.06	gold quality
pleura	UBERON:0000977	79.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.95	gold quality
epithelium of nasopharynx	UBERON:0001951	78.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.82	gold quality
palpebral conjunctiva	UBERON:0001812	78.65	gold quality
skin of hip	UBERON:0001554	78.30	gold quality
rectum	UBERON:0001052	78.28	gold quality
penis	UBERON:0000989	78.22	gold quality
large intestine	UBERON:0000059	77.90	gold quality
upper lobe of lung	UBERON:0008948	77.90	gold quality
colon	UBERON:0001155	77.85	gold quality
islet of Langerhans	UBERON:0000006	77.56	gold quality
upper lobe of left lung	UBERON:0008952	77.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.50	gold quality
endometrium	UBERON:0001295	77.45	gold quality
transverse colon	UBERON:0001157	77.38	gold quality
upper leg skin	UBERON:0004262	77.06	gold quality
caudate nucleus	UBERON:0001873	76.72	gold quality
colonic epithelium	UBERON:0000397	76.09	gold quality
jejunal mucosa	UBERON:0000399	76.00	gold quality
intestine	UBERON:0000160	75.99	gold quality
parietal pleura	UBERON:0002400	75.89	gold quality
female reproductive system	UBERON:0000474	75.50	gold quality
skin of abdomen	UBERON:0001416	75.19	gold quality
zone of skin	UBERON:0000014	75.04	gold quality
body of uterus	UBERON:0009853	74.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.66	silver quality
uterus	UBERON:0000995	74.57	gold quality
ectocervix	UBERON:0012249	74.56	gold quality
skin of leg	UBERON:0001511	74.55	gold quality
trigeminal ganglion	UBERON:0001675	74.51	gold quality
lung	UBERON:0002048	74.46	gold quality
putamen	UBERON:0001874	74.00	gold quality
eye	UBERON:0000970	73.83	gold quality
primary visual cortex	UBERON:0002436	73.80	gold quality
jejunum	UBERON:0002115	73.74	gold quality
esophagus	UBERON:0001043	73.37	gold quality
myometrium	UBERON:0001296	73.32	gold quality
entorhinal cortex	UBERON:0002728	73.19	silver quality
ventricular zone	UBERON:0003053	73.03	gold quality
monocyte	CL:0000576	72.98	gold quality
ovary	UBERON:0000992	72.89	gold quality
left ovary	UBERON:0002119	72.70	gold quality
middle temporal gyrus	UBERON:0002771	72.69	silver quality
mononuclear cell	CL:0000842	72.54	gold quality
ileal mucosa	UBERON:0000331	72.49	silver quality
smooth muscle tissue	UBERON:0001135	72.42	gold quality
amygdala	UBERON:0001876	72.31	gold quality
prostate gland	UBERON:0002367	72.19	gold quality
leukocyte	CL:0000738	72.10	gold quality
temporal lobe	UBERON:0001871	72.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.64	gold quality
pancreas	UBERON:0001264	71.09	gold quality
occipital lobe	UBERON:0002021	71.08	gold quality
mucosa of transverse colon	UBERON:0004991	71.02	gold quality
body of tongue	UBERON:0011876	70.97	silver quality
tendon	UBERON:0000043	70.90	gold quality
right ovary	UBERON:0002118	70.67	gold quality
nasal cavity mucosa	UBERON:0001826	69.91	gold quality
endocervix	UBERON:0000458	69.87	gold quality
vastus lateralis	UBERON:0001379	69.83	silver quality
ganglionic eminence	UBERON:0004023	69.77	gold quality
small intestine	UBERON:0002108	69.71	gold quality
dorsal root ganglion	UBERON:0000044	69.40	gold quality
telencephalon	UBERON:0001893	69.34	gold quality
tibial nerve	UBERON:0001323	69.24	gold quality
mammalian vulva	UBERON:0000997	69.20	gold quality
superior vestibular nucleus	UBERON:0007227	69.13	silver quality
duodenum	UBERON:0002114	68.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.66	gold quality
Ammon’s horn	UBERON:0001954	68.61	gold quality
quadriceps femoris	UBERON:0001377	68.39	gold quality
corpus callosum	UBERON:0002336	68.11	gold quality
body of pancreas	UBERON:0001150	68.00	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	201.95
E-MTAB-7008	yes	171.64
E-GEOD-81547	yes	9.94
E-ANND-3	yes	4.28

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Basal ganglia	tissue	32.8	low
Nucleus accumbens	tissue	30.6
Placenta	tissue	23.9	high
Putamen	tissue	22.8
Midbrain	tissue	21.4
Locus coeruleus	tissue	19.1
Spinal cord	tissue	18.5
Esophagus	tissue	18.1	medium
Septum	tissue	17.9
Ventral forebrain	tissue	17.3
Pons	tissue	16.2
Caudate putamen	tissue	15.2
Thalamus	tissue	14.2
Periaqueductal gray	tissue	13.5
Hippocampus	tissue	13.4	low
Substantia nigra	tissue	13.3
Medulla oblongata	tissue	12.0
Hypothalamus	tissue	11.2
Superior colliculi	tissue	10.4
Hippocampal formation	tissue	9.1
Skin 1	tissue	8.4	medium
Retina	tissue	8.3
Vagina	tissue	8.3	low
Colon	tissue	8.1	low
Ovary	tissue	7.5	not detected
Skeletal muscle	tissue	7.3	medium
Prostate	tissue	7.3	medium
Corpus callosum	tissue	6.6
Postcentral gyrus	tissue	6.5
Rectum	tissue	6.3	medium
Endometrium 1	tissue	6.1	low
Small intestine	tissue	5.8	medium
Bone marrow	tissue	5.4	not detected
Amygdala	tissue	4.3
Smooth muscle	tissue	4.2	medium
Lung	tissue	4.2	medium
Cerebral cortex	tissue	4.0	medium
Occipital cortex	tissue	4.0
Tongue	tissue	3.2
Entorhinal cortex	tissue	3.2
Pancreas	tissue	3.1	low
Choroid plexus	tissue	3.1
Duodenum	tissue	3.0	low
Somatosensory cortex	tissue	3.0
Heart muscle	tissue	2.7	medium
Temporal cortex	tissue	2.7
Cervix	tissue	2.6	not detected
Tonsil	tissue	2.5	medium
Retrosplenial and cingulate cortex	tissue	2.5
Olfactory bulb	tissue	2.4
Retrosplenial cortex	tissue	2.4
Urinary bladder	tissue	2.3	low
Motor cortex	tissue	2.2
Prefrontal cortex	tissue	2.1
Seminal vesicle	tissue	2.1	low
Spleen	tissue	2.1	medium
Appendix	tissue	2.1	low
Insular cortex	tissue	2.0
Frontal cortex	tissue	1.9
Gallbladder	tissue	1.9	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal spinal cord (18.5), Ventromedial nucleus (17.9), Caudate nucleus (17.5), Ventral spinal cord (17.3), Arcuate nucleus (15.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

Targeting P2RY1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 203 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038

Functional genomics

gnomAD constraint: pLI 0.00204, LOEUF 0.933, missense Z 1.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000305097 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:152,835,783–152,835,983	98 / 87.7	1.12	no
3:152,835,984–152,836,026	6 / 21.1	0.28	yes (p 1.0e-03)
3:152,836,027–152,836,901	291 / 361.6	0.80	no

Literature-anchored findings (GeneRIF, showing 40)

• expression profile in human peripheral tissues and brain regions using PCR (PMID:11690642)
• Inhibition of platelet P2Y12 and alpha2A receptor signaling by cGMP-dependent protein kinase. (PMID:12147294)
• immunolocalization of P2Y1 and TPalpha receptors in platelets revealed that while present at the platelet surface, both receptors were abundantly represented inside the platelet - in membranes of alpha-granules and elements of the open-canalicular system (PMID:12393588)
• Human keratinocytes express multiple P2Y-receptors: evidence for functional P2Y1, P2Y2, and P2Y4 receptors. (PMID:12603858)
• the P2Y(1) purinoceptor and the P2Y(12)receptor appear to be involved in ADP-induced platelet shape change, an early phase of platelet activation that precedes aggregation (PMID:12623443)
• Different purinergic receptors have different functional roles in human epidermis with P2Y1 and P2Y2 receptors controlling proliferation, while P2X5 and P2X7 receptors control early differentiation, terminal differentiation and death of keratinocytes. (PMID:12787128)
• Non-melanoma skin cancers express functional purinergic receptors and that P2X7 receptor agonists significantly reduce cell numbers in vitro. (PMID:12880424)
• Supports P2Y(12) as a drug target compared with P2Y(1). (PMID:14644082)
• Whereas P2RY1 antagonism did not affect collagen or thrombin-induced thrombin generation, P2RY12 antagonism did decrease both, suggesting that P2RY12, but not P2RY1, is responsible for the potentiation of agonist-induced platelet procoagulant activity. (PMID:15099288)
• Src kinase is activated through P2Y(1) but not P2Y(12) (PMID:15187029)
• both P2Y12 and P2Y1 contribute to ADP-potentiation of platelet-derived microparticles generation induced by collagen (PMID:15203713)
• ADP signaling through P2Y(1) may contribute to the initial stages of platelet adhesion and activation mediated by immobilized VWF, and through P2Y(12) to sustained thrombus formation. (PMID:15284110)
• Basal activity of the P2Y(1) receptor is maintained by paracrine or autocrine release of receptor agonists. (PMID:15496502)
• Results show that the two arginine residues (R333R334) in the carboxyl terminus of the human P2Y(1) ADP receptor are essential for G(q) coupling. (PMID:15509659)
• The P2Y1 has an exclusive vascular distribution. (PMID:15590415)
• Agonist-induced P2Y1 receptor desensitization was accompanied by its internalization in platelets and transfected cells. (PMID:15602005)
• both P2Y(1) and P2Y(12) desensitize in human platelets; P2Y(12), but not P2Y(1), desensitization is mediated by GRKs (PMID:15665114)
• Induction of the osmolyte permeability in Plasmodium-infected erythrocytes involves autocrine purinoceptor signaling. (PMID:16267125)
• We conclude that lipid rafts play a significant role in the regulation of P2X1 but not P2Y1 receptors in human platelets and that a reserve of non-functional P2X1 receptors may exist. (PMID:16546137)
• the A1622G dimorphism in P2Y1 is not associated with ADP-induced platelet activation/aggregation after treatment with clopidogrel (PMID:16634769)
• Stimulation of ARO cells evidenced a major involvement of P2Y1 and P2Y2 receptors in controlling the Hsp90 activation. P2Y1 and P2Y2 resulted significantly upregulated in sample biopsies from different thyroid tumors. (PMID:16741950)
• This study therefore is the first to reveal distinct roles for PKC isoforms in the regulation of platelet P2Y receptor function and trafficking. (PMID:16804093)
• results suggest that the interaction of calmodulin with the P2Y1 C-terminal tail may regulate P2Y1-dependent platelet aggregation (PMID:16848759)
• To determine if polymorphisms in P2X7 are associated with increased risk of TB. The 1513C allele increases susceptibility to extrapulmonary TB. (PMID:17095747)
• Presence of the P2Y1 893CC genotype appears to confer an attenuated antiplatelet effect during aspirin treatment in healthy Chinese volunteers. (PMID:17559347)
• oligomerization of the P2Y11 receptor with the P2Y1 receptor controls the internalization and ligand selectivity of the P2Y11 receptor (PMID:17824841)
• These results highlight a role of P2Y(1)R in EGFR-dependent epithelial cell proliferation. P2Y(1)R could potentially mediate both trophic stimuli of basally released nucleotides and first-line mitogenic stimulation upon tissue damage. (PMID:18057028)
• ADP promotes human endothelial cell migration by activating P2Y1 receptor-mediated MAPK pathways, possibly contributing to reendothelialization and angiogenesis after vascular injury (PMID:18174464)
• analysis of constitutive and agonist-induced dimerizations of the P2Y1 receptor (PMID:18270199)
• Olfactory nerve terminals release not only glutamate, but also ATP, which activates P2Y(1) receptors. (PMID:18310463)
• The interaction between A(1) and P2Y(1) receptors may play an important role in the purinergic signaling cascade in astrocytes (PMID:18500760)
• stress induces release of ATP, which in turn mediates Rho kinase activation through the P2Y1 receptor, resulting in the up-regulation of OPN [and] could play a significant role in alveolar bone resorption (PMID:18502966)
• In intact human vascular smooth muscle the association of the P2Y(1)R to membrane rafts, highlighting the role of this microdomain in P2Y(1)R signaling. (PMID:18799799)
• genetic polymorphisms in ITGA2 and P2RY1 combine with plasma VWF:Ag levels to modulate baseline platelet reactivity in response to collagen plus EPI, while genetic differences in P2RY1 and GP1BA significantly effect platelet responses to collagen plus ADP (PMID:19740098)
• Data show that ADP significantly increased VEGF, but not endostatin, release from platelets, and that both P2Y(1) and P2Y(12) receptor antagonism inhibited this release. (PMID:20063989)
• These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of G-protein coupled receptors. (PMID:20070609)
• Data show that compound 3 was active in changing intracelluular calcium in 1321N1 human astrocytoma cells stably expressing the hP2Y1 receptor. (PMID:20192270)
• Evaluation of antiplatelet agents in open flow systems demonstrates that inhibition of either ADP by apyrase or antagonism of P2X(1) signaling had no inhibitory effect on platelet accumulation. (PMID:20473398)
• analysis of a novel Gi, P2Y-independent signaling pathway mediating Akt phosphorylation in response to thrombin receptors (PMID:20586915)
• Adenosine triphosphate (ATP) acts trophically in brain neurons via its purinergic receptor P2Y1 to regulate gene expression of synaptic transmission and transduction. (PMID:20847060)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	p2ry1	ENSDARG00000105281
mus_musculus	P2ry1	ENSMUSG00000027765
rattus_norvegicus	P2ry1	ENSRNOG00000014232

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), FFAR3 (ENSG00000185897), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105049) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased bleeding time	2
decreased platelet aggregation	2
abnormal thrombolysis	1
decreased susceptibility to induced thrombosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P34996	99.7%	Diamond
Meleagris gallopavo	P49652	99.7%	Diamond
Cricetulus griseus	P58825	98.8%	Diamond
Meriones unguiculatus	Q99PE3	98.8%	Diamond
Papio hamadryas	P56488	97.9%	Diamond
Bos taurus	P48042	96.8%	Diamond
Macaca mulatta	P35366	96.2%	Diamond
Cavia porcellus	P59902	96.2%	Diamond
Sus scrofa	P50132	95.6%	Diamond
Cricetulus longicaudatus	Q00991	89.5%	Diamond
Callorhinchus milii	A0A4W3GG95	73.4%	Diamond
Xenopus laevis	P47749	61.0%	Diamond

Protein

Protein identifiers

P2Y purinoceptor 1 — P47900 (reviewed: P47900)

Alternative names: ADP receptor, Purinergic receptor

All UniProt accessions (1): P47900

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for extracellular adenine nucleotides such as ADP. In platelets, binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and ultimately platelet aggregation.

Subcellular location. Cell membrane.

Activity regulation. ATP functions as antagonist and inhibits ADP-induced mobilization of Ca(2+). The P2Y1 receptor-specific antagonists A3P5PS, A3P5P and A2P5P inhibit downstream signaling mediated by mobilization of Ca(2+) from intracellular stores, and platelet shape changes in response to extracellular ADP.

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

RefSeq proteins (1): NP_002554* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000142	P2Y1_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (56 total): helix 15, topological domain 8, transmembrane region 7, mutagenesis site 6, binding site 5, turn 5, glycosylation site 4, disulfide bond 2, strand 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
4XNV	The human P2Y1 receptor in complex with BPTU	X-RAY DIFFRACTION	2.2
4XNW	The human P2Y1 receptor in complex with MRS2500	X-RAY DIFFRACTION	2.7
9JCL	ADP-bound purinergic receptor 1 with L266P mutant in complex with miniGs/q	ELECTRON MICROSCOPY	2.76
7XXH	Cryo-EM structure of the purinergic receptor P2Y1R in complex with 2MeSADP and G11	ELECTRON MICROSCOPY	2.9
8WJX	ADP-bound purinergic receptor 1 in complex with miniGs/q	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47900-F1	86.12	0.63

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 7XXH, 8WJX, 9JCL

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Adenosine and adenine nucleotide receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (5)

Position	Role
46	ADP
203–205	ADP
283–287	ADP
303–306	ADP
310	ADP

Disulfide bonds (2)

Type	Positions
Disulfide bond	42–296, 124–202

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	11, 27, 113, 197

Mutagenesis-validated functional residues (6)

Position	Phenotype
44	loss of adp analog binding.
110	loss of adp analog binding.
203	loss of adp analog binding.
205	loss of adp analog binding.
283	loss of adp analog binding.
306	strongly decreased affinity for adp analog.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-416476	G alpha (q) signalling events	curated
R-HSA-417957	P2Y receptors	curated
R-HSA-418592	ADP signalling through P2Y purinoceptor 1	electronic
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-109582	Hemostasis	—
R-HSA-418038	Nucleotide-like (purinergic) receptors	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-162582	Signal Transduction	—
R-HSA-392518	Signal amplification	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 315 (showing top): LEE_SP4_THYMOCYTE, GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, REACTOME_P2Y_RECEPTORS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_EXOCYTOSIS

GO Biological Process (30): G protein-coupled adenosine receptor signaling pathway (GO:0001973), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), glial cell migration (GO:0008347), regulation of cell shape (GO:0008360), response to mechanical stimulus (GO:0009612), negative regulation of norepinephrine secretion (GO:0010700), signal transduction involved in regulation of gene expression (GO:0023019), platelet activation (GO:0030168), positive regulation of inositol trisphosphate biosynthetic process (GO:0032962), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589), eating behavior (GO:0042755), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of hormone secretion (GO:0046887), positive regulation of penile erection (GO:0060406), positive regulation of ERK1 and ERK2 cascade (GO:0070374), response to growth factor (GO:0070848), cellular response to ATP (GO:0071318), cellular response to purine-containing compound (GO:0071415), protein localization to plasma membrane (GO:0072659), relaxation of muscle (GO:0090075), blood vessel diameter maintenance (GO:0097746), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509), regulation of synaptic vesicle exocytosis (GO:2000300), signal transduction (GO:0007165), blood coagulation (GO:0007596), hemostasis (GO:0007599)

GO Molecular Function (13): G protein-coupled ADP receptor activity (GO:0001621), ATP binding (GO:0005524), signaling receptor regulator activity (GO:0030545), A1 adenosine receptor binding (GO:0031686), signaling receptor activity (GO:0038023), ADP binding (GO:0043531), G protein-coupled purinergic nucleotide receptor activity (GO:0045028), G protein-coupled ATP receptor activity (GO:0045031), protein heterodimerization activity (GO:0046982), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (12): plasma membrane (GO:0005886), cilium (GO:0005929), cell surface (GO:0009986), postsynaptic density (GO:0014069), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), dendrite (GO:0030425), cell body (GO:0044297), postsynaptic membrane (GO:0045211), presynaptic active zone membrane (GO:0048787), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Nucleotide-like (purinergic) receptors	1
Signal amplification	1
Signal Transduction	1
GPCR ligand binding	1
Platelet activation, signaling and aggregation	1
Class A/1 (Rhodopsin-like receptors)	1
Hemostasis	1

GO top-level categories

showing 60 of 75 GO namespaces:

Category	Terms
signal transduction	3
cellular anatomical structure	3
G protein-coupled receptor activity	2
G protein-coupled receptor signaling pathway	2
regulation of biological quality	2
G protein-coupled purinergic nucleotide receptor activity	2
adenyl ribonucleotide binding	2
anion binding	2
plasma membrane region	2
synaptic membrane	2
G protein-coupled purinergic receptor signaling pathway	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
cell migration	1
gliogenesis	1
regulation of cell morphogenesis	1
response to external stimulus	1
response to abiotic stimulus	1
regulation of norepinephrine secretion	1
negative regulation of catecholamine secretion	1
norepinephrine secretion	1
regulation of gene expression	1
cell activation	1
blood coagulation	1
inositol trisphosphate biosynthetic process	1
regulation of inositol trisphosphate biosynthetic process	1
positive regulation of inositol phosphate biosynthetic process	1
purinergic nucleotide receptor signaling pathway	1
feeding behavior	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
positive regulation of cell communication	1
positive regulation of signaling	1
hormone secretion	1
regulation of hormone secretion	1
positive regulation of secretion by cell	1
penile erection	1
positive regulation of multicellular organismal process	1
regulation of penile erection	1
positive regulation of reproductive process	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
response to endogenous stimulus	1
ADP binding	1
purine ribonucleoside triphosphate binding	1
signaling receptor activity	1
molecular function regulator activity	1
adenosine receptor binding	1
molecular transducer activity	1
purinergic nucleotide receptor activity	1
G protein-coupled purinergic nucleotide receptor signaling pathway	1
protein dimerization activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transmembrane signaling receptor activity	1
binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 55 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to purine-containing compound	BP	mutant phenotype
phospholipase C-activating G protein-coupled receptor signaling pathway	BP	mutant phenotype
regulation of cell shape	BP	mutant phenotype
cell surface	CC	high-throughput assay
cilium	CC	direct assay
plasma membrane	CC	direct assay
ATP binding	MF	mutant phenotype
G protein-coupled ADP receptor activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,738 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RY1	P2RX1	P51575	937
P2RY1	ENTPD2	Q9Y5L3	843
P2RY1	ENTPD1	P49961	790
P2RY1	SIX3	O95343	755
P2RY1	P2RX2	Q9UBL9	669
P2RY1	ITGA2B	P08514	661
P2RY1	P2RX4	Q99571	656
P2RY1	P2RX7	Q99572	655
P2RY1	P2RX3	P56373	654
P2RY1	GP6	Q9HCN6	654
P2RY1	ENTPD8	Q5MY95	641
P2RY1	PPAN	Q9NQ55	639
P2RY1	ENTPD3	O75355	606
P2RY1	PAX6	P26367	603
P2RY1	P2RY12	Q9H244	602

IntAct

Human interaction partners of P2RY1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
NHERF1	direct interaction	0.560	2
SLC19A2	association	0.530	3
EI24	association	0.350	1
GPC4	association	0.350	1

BioGRID (56 interactions; top human partners by supporting records): CMIP (Affinity Capture-MS; 3 records), ATP11C (Affinity Capture-MS; 2 records), GPM6A (Affinity Capture-MS; 2 records), MIB2 (Affinity Capture-MS; 2 records), SLC19A2 (Affinity Capture-MS; 2 records), ADORA1 (Affinity Capture-Western), ATP5A1 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS), ATP5O (Affinity Capture-MS), CD97 (Affinity Capture-MS), CERS2 (Affinity Capture-MS), CERS6 (Affinity Capture-MS)

SIGNOR signaling

9 signaling interactions:

A	Effect	B	Mechanism
P2RY1	“up-regulates activity”	GNAS	binding
P2RY1	“up-regulates activity”	GNAL	binding
P2RY1	“up-regulates activity”	GNAI1	binding
P2RY1	“up-regulates activity”	GNAO1	binding
P2RY1	“up-regulates activity”	GNAZ	binding
P2RY1	“up-regulates activity”	GNA15	binding
P2RY1	“up-regulates activity”	GNA12	binding
P2RY1	“up-regulates activity”	GNA13	binding
ADP	“up-regulates activity”	P2RY1	“chemical activation”

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ ADORA1-P2RY1 complex	2	P2RY1, ADORA1
P2RY1-P2RY11 complex	2	P2RY1, P2RY11
NHERF2-P2RY1 complex	2	NHERF2, P2RY1
P2RY1-TMED2 complex	2	P2RY1, TMED2
P2Y purinoceptor 1	1	P2RY1

Disease & clinical

Genetic variants

Variant evidence for P2RY1: 24 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	3
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 16 predictions of 114):

Position(s)	Effect	Δscore	Sites
3:152839579	acceptor_gain	0.8900
3:152835247	donor_gain	0.7700
3:152836908	donor_gain	0.6600
3:152835310–152835311	donor_loss	0.6400	6
3:152835309	donor_loss	0.6300	2
3:152836803	donor_gain	0.6300
3:152835309	donor_loss	0.6200
3:152836947	donor_gain	0.5900
3:152839537	acceptor_gain	0.5900
3:152835308	donor_loss	0.5800

AlphaMissense

1,184 missense substitutions predicted likely pathogenic (of 2,443 scored), across 272 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M90	9	0.887	0.993
D97	8	0.998	0.999
N69	8	0.995	0.999
D204	8	0.995	0.999
D320	8	0.990	0.998
F269	8	0.984	0.999
F131	8	0.981	0.999
H277	8	0.980	0.997
F141	8	0.978	0.997
N134	8	0.967	0.999
N316	8	0.961	0.999
F76	8	0.951	0.994
N283	8	0.949	0.997
F331	8	0.949	0.997
F226	8	0.946	0.997
F49	8	0.944	0.996
S146	8	0.942	0.999
S138	8	0.936	0.998
H132	8	0.932	0.983
S314	8	0.903	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	7.76e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000289

Disease associations

OMIM: gene MIM:601167 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST007576_76	Chronotype	9e-10
GCST003723_2	Serum sulfate level	3e-7
GCST001535_6	Immune reponse to smallpox (secreted IL-2)	4e-7
GCST004100_2	Body mass index (change over time) in gastrointestinal cancer or chronic obstructive pulmonary disease	6e-7
GCST009391_1137	Metabolite levels	2e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007864	sulfate measurement
EFO:0005937	longitudinal BMI measurement
EFO:0008328	chronotype measurement
EFO:0010364	lysophosphatidylcholine 20:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4315 (SINGLE PROTEIN), CHEMBL4524011 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the P2RY1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
DIQUAFOSOL TETRASODIUM	Small molecule	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 463,070 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL752	ADENOSINE PHOSPHATE	4	166,120
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	296,539
CHEMBL457077	SALVIANOLIC ACID A	1	411

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1065776	Efficacy	3	aspirin	Myocardial Infarction

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1065776	P2RY1	3	1.88	1	aspirin

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

5 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1065776	aspirin	Efficacy	Genotype CT is associated with increased net decrease in AA-induced platelet aggregation after aspirin treatment when treated with aspirin in healthy individuals as compared to genotype CC.	PMID:17559347
rs1371097	aspirin	Efficacy	Allele T is associated with decreased clinical benefit to aspirin in people with Stroke as compared to allele C.	PMID:40290439
rs1371097	aspirin	Efficacy	Allele T is associated with decreased clinical benefit to aspirin in people with Stroke as compared to allele C.	PMID:40644802
rs1065776	aspirin	Efficacy	Genotype CT is associated with increased likelihood of Thromboembolism or platelet reactivity when treated with aspirin in children with Heart Diseases as compared to genotype CC.	PMID:42499276
rs1065776	aspirin	Efficacy	Genotype CT is associated with increased risk of aspirin-resistant phenotype when treated with aspirin as compared to genotype TT.	PMID:15757620

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — P2Y receptors

Most potent curated ligand interactions (35 total), top 25:

Ligand	Action	Affinity	Parameter
[32P]MRS2500	Antagonist	9.4	pKd
MRS2365	Agonist	9.4	pEC50
MRS2500	Antagonist	9.1	pKi
BMS compound 4c	Antagonist	8.2	pKi
2-Cl-ADP(α-BH3)	Agonist	8.15	pEC50
[3H]MRS2279	Antagonist	8.1	pKd
2’,3’-ddATP	Partial agonist	8.0	pIC50
Pfizer compound 67 [PMID:18445527]	Antagonist	8.0	pKi
MRS2279	Antagonist	7.9	pKi
ATP	Partial agonist	7.8	pIC50
dATPαS	Partial agonist	7.7	pIC50
2MeSATP	Partial agonist	7.6	pIC50
MRS2298	Antagonist	7.5	pKi
ATPγS	Partial agonist	7.4	pIC50
compound 3a [PMID: 22873688]	Full agonist	7.4	pEC50
ADPβS	Agonist	7.3	pEC50
[3H]2MeSADP	Agonist	7.3	pKd
Pfizer compound 11 [PMID:18445527]	Antagonist	7.3	pKi
Ap3a	Agonist	7.22	pEC50
GlaxoSmithKline compound 6i [PMID:18926700]	Antagonist	7.2	pKi
ADP	Full agonist	7.2	pIC50
MRS2496	Antagonist	7.1	pKi
MRS2179	Antagonist	7.1	pKi
2MeSADP	Full agonist	7.0	pIC50
BMS compound 16 [PMID:23368907]	Negative	6.92	pKi

Binding affinities (BindingDB)

820 measured of 883 human assays (894 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(2-chloro-1,3-thiazol-4-yl)urea	IC50	0.03 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-cyano-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.04 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.04 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(6-fluoro-1,3-benzothiazol-2-yl)urea	IC50	0.06 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1’-(2,2-dimethylpropyl)-4-(trifluoromethyl)-1-[2-[[5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	0.08 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea	IC50	0.08 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[1’-(2,2-dimethylpropyl)-5-fluoro-4-(4-fluorophenyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.09 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)-3-[2-[1’-(2,2-dimethylpropyl)-5-fluoro-4-(4-fluorophenyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	IC50	0.12 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[1’-(2,2-dimethylpropyl)-4-(dimethylsulfamoyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.13 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[1’-(2,2-dimethylpropyl)-7-hydroxy-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.14 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
CHEMBL3314287	IC50	0.14 nM
methyl 1’-(2,2-dimethylpropyl)-7-hydroxy-1-[2-[[4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]spiro[2H-indole-3,4’-piperidine]-4-carboxylate	IC50	0.15 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-(4-chlorophenyl)-1’-(2,2-dimethylpropyl)-5-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.16 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-(6-chloro-1,3-benzothiazol-2-yl)-3-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	IC50	0.17 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1’-(2,2-dimethylpropyl)-1-[2-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]phenyl]-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	0.19 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
4-chloro-1’-(2,2-dimethylpropyl)-1-[2-[[5-(2,5-dimethylpyrazol-3-yl)-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	0.2 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	0.21 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.23 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
methyl 1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-4-carboxylate	IC50	0.32 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-4-carbonitrile	IC50	0.34 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[1’-(2,2-dimethylpropyl)-4-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	0.37 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
CHEMBL2112093	EC50	0.4 nM
4-chloro-1’-(2,2-dimethylpropyl)-1-[2-[[5-[4-(trifluoromethoxy)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	0.63 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-(4-chlorophenyl)-5-fluoro-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	IC50	1.1 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
US9428504, 133	KI	1.2 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
US9540323, 269	KI	1.2 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
4-chloro-1’-(2,2-dimethylpropyl)-1-[2-[(5-pyrazin-2-yl-1,3,4-thiadiazol-2-yl)amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	1.5 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
4-chloro-1-[2-[[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	1.6 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
(1’S,2’R,3’S,4’R,5’S)-4-(6-Amino-2-chloro-9H-purin-9-yl)-1-[phosphoryloxymethyl]bicyclo[3.1.0]hexane-2,3-diol	EC50	1.89 nM
1-[2-[1’-(2,2-dimethylpropyl)-4-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(3-propan-2-yl-1,2,4-thiadiazol-5-yl)urea	KI	1.9 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
CHEMBL3104624	IC50	2.2 nM
CHEMBL2309024	EC50	2.6 nM
1’-(2,2-dimethylpropyl)-4-fluoro-1-[2-[[5-[4-(trifluoromethoxy)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	2.7 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1’-(2,2-dimethylpropyl)-7-hydroxy-1-[2-[[5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-4-carbonitrile	IC50	3 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
triPhosphoric acid -[4-(6-amino-2-chloro-purin-9-yl)-2,3-dihydroxy-bicyclo[3.1.0]hex-1-ylmethyl] ester	EC50	3 nM
1-[2-(3,3-diethyl-4-fluoro-7-hydroxy-2H-indol-1-yl)phenyl]-3-(4-ethylphenyl)urea	KI	3.1 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
1-(2,4-difluorophenyl)-3-[2-[1’-(2,2-dimethylpropyl)-7-hydroxy-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	KI	3.2 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
4-chloro-1’-(2,2-dimethylpropyl)-1-[2-[[5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	IC50	3.3 nM	US-9120798: Amino-heteroaryl 7-hydroxy-spiropiperidine indolinyl antagonists of P2Y1 receptor
1-(4-tert-butylphenyl)-3-[2-[1’-(2,2-dimethylpropyl)-7-hydroxy-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-1-yl]-3-pyridinyl]urea	KI	3.3 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(3-methyl-1,2,4-thiadiazol-5-yl)urea	KI	3.3 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-(2-chloro-1,3-thiazol-4-yl)-3-[2-(3,3-diethyl-4-fluoro-7-hydroxy-2H-indol-1-yl)phenyl]urea	KI	3.3 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
1-[2-[4-(6-fluoro-5-methyl-3-pyridinyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	KI	3.3 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
1-[2-[4-(diethylsulfamoyl)-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	KI	3.4 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[4-[1-(2,2-dimethylpropyl)piperidin-4-yl]phenyl]-3-[2-[7-hydroxy-3,3-dimethyl-4-(trifluoromethyl)-2H-indol-1-yl]phenyl]urea	KI	3.4 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
US9540323, 124	KI	3.4 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
1-(4-tert-butylphenyl)-3-[2-[4-(diethylsulfamoyl)-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	KI	3.5 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-(3,3-diethyl-4-fluoro-7-hydroxy-2H-indol-1-yl)phenyl]-3-[4-[1-(2,2-dimethylpropyl)pyrrolidin-2-yl]phenyl]urea	KI	3.6 nM	US-9540323: 7-hydroxy-indolinyl antagonists of P2Y1 receptor
1-(6-chloro-1,3-benzothiazol-2-yl)-3-[2-[1’-(2,2-dimethylpropyl)-4-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	KI	3.7 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-[2-[1’-(2,2-dimethylpropyl)-4-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(6-methyl-1,3-benzothiazol-2-yl)urea	KI	3.7 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor
1-(2-chloro-1,3-thiazol-4-yl)-3-[2-[4-cyano-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	KI	3.7 nM	US-9428504: 7-hydroxy-spiropipiperidine indolinyl antagonists of P2Y1 receptor

ChEMBL bioactivities

1183 potent at pChembl≥5 of 1210 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL3314307
10.52	IC50	0.03	nM	CHEMBL3287050
10.52	IC50	0.03	nM	CHEMBL3314305
10.40	IC50	0.04	nM	CHEMBL3287043
10.40	IC50	0.04	nM	CHEMBL3287044
10.40	IC50	0.04	nM	CHEMBL3314308
10.30	IC50	0.05	nM	CHEMBL3314291
10.22	IC50	0.06	nM	CHEMBL3287049
10.10	IC50	0.08	nM	CHEMBL3263066
10.10	IC50	0.08	nM	CHEMBL3287051
10.10	IC50	0.08	nM	CHEMBL3314306
10.05	IC50	0.09	nM	CHEMBL3314290
10.05	IC50	0.09	nM	CHEMBL3314320
9.92	IC50	0.12	nM	CHEMBL3263056
9.92	IC50	0.12	nM	CHEMBL3314321
9.89	IC50	0.13	nM	CHEMBL3287042
9.89	IC50	0.13	nM	CHEMBL3314299
9.89	IC50	0.13	nM	CHEMBL3314304
9.85	IC50	0.14	nM	CHEMBL3287041
9.85	IC50	0.14	nM	CHEMBL3314287
9.82	IC50	0.15	nM	CHEMBL3287052
9.82	IC50	0.15	nM	CHEMBL3314297
9.80	IC50	0.16	nM	CHEMBL3314319
9.77	IC50	0.17	nM	CHEMBL3287040
9.72	IC50	0.19	nM	CHEMBL3263057
9.70	IC50	0.2	nM	CHEMBL3263076
9.68	IC50	0.21	nM	CHEMBL3263067
9.64	IC50	0.23	nM	CHEMBL3287047
9.64	IC50	0.23	nM	CHEMBL3314309
9.52	IC50	0.3	nM	CHEMBL3314317
9.49	IC50	0.32	nM	CHEMBL3263069
9.48	IC50	0.33	nM	CHEMBL3314298
9.47	IC50	0.34	nM	CHEMBL3263068
9.43	IC50	0.37	nM	CHEMBL3287045
9.43	IC50	0.37	nM	CHEMBL3314295
9.43	IC50	0.37	nM	CHEMBL3314296
9.41	IC50	0.39	nM	CHEMBL3314288
9.40	EC50	0.4	nM	CHEMBL2112093
9.40	EC50	0.4	nM	CHEMBL2373948
9.35	IC50	0.45	nM	CHEMBL3314310
9.33	IC50	0.47	nM	CHEMBL3314316
9.29	IC50	0.51	nM	CHEMBL3314315
9.28	IC50	0.52	nM	CHEMBL3314301
9.24	IC50	0.57	nM	CHEMBL3314303
9.24	IC50	0.57	nM	CHEMBL3314314
9.20	IC50	0.63	nM	CHEMBL3263071
9.11	Ki	0.78	nM	CHEMBL444278
9.10	Ki	0.79	nM	CHEMBL444278
8.97	IC50	1.06	nM	CHEMBL3314311
8.96	IC50	1.1	nM	CHEMBL3314311

PubChem BioAssay actives

690 with measured affinity, of 1123 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
1-[4-[1-(2,2-dimethylpropyl)pyrrolidin-2-yl]phenyl]-3-[2-[4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	<0.0001	uM
1-(2-chloro-1,3-thiazol-4-yl)-3-[2-[4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	<0.0001	uM
1-[2-[4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-[1-(2-methylpropyl)pyrrolidin-2-yl]phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	<0.0001	uM
1-[2-[4-cyano-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	<0.0001	uM
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(2-chloro-1,3-thiazol-4-yl)urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	<0.0001	uM
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	<0.0001	uM
1-[2-[1’-(2,2-dimethylpropyl)-5-fluoro-4-(4-fluorophenyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-[2-[4-(4-chlorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-[2-[4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-(2-methyl-1,3-thiazol-4-yl)urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-[2-(4-chloro-7-hydroxy-3,3-dimethyl-2H-indol-1-yl)phenyl]-3-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)urea	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0001	uM
1’-(2,2-dimethylpropyl)-4-(trifluoromethyl)-1-[2-[[5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0001	uM
1-[2-[1’-(2,2-dimethylpropyl)-7-hydroxy-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0001	uM
ethyl 4-chloro-7-hydroxy-3-methyl-1-[2-[[4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]-2H-indole-3-carboxylate	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-[2-[4-(3-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)-3-[2-[4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
ethyl 4-chloro-1-[2-[(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)carbamoylamino]phenyl]-7-hydroxy-3-methyl-2H-indole-3-carboxylate	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
methyl 1’-(2,2-dimethylpropyl)-7-hydroxy-1-[2-[[4-(trifluoromethoxy)phenyl]carbamoylamino]phenyl]spiro[2H-indole-3,4’-piperidine]-4-carboxylate	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0001	uM
1-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)-3-[2-[1’-(2,2-dimethylpropyl)-5-fluoro-4-(4-fluorophenyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0001	uM
1-[2-[1’-(2,2-dimethylpropyl)-4-(dimethylsulfamoyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0001	uM
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(6-fluoro-1,3-benzothiazol-2-yl)urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0001	uM
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0001	uM
1-[2-[4-(4-chlorophenyl)-1’-(2,2-dimethylpropyl)-5-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0002	uM
4-chloro-1’-(2,2-dimethylpropyl)-1-[2-[[5-(2,5-dimethylpyrazol-3-yl)-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0002	uM
1-[2-[1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0002	uM
1’-(2,2-dimethylpropyl)-1-[2-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]phenyl]-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-7-ol	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0002	uM
1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)-4-(trifluoromethyl)spiro[2H-indole-3,4’-piperidine]-7-ol	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0002	uM
1-[2-[5-fluoro-4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0002	uM
1-(6-chloro-1,3-benzothiazol-2-yl)-3-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0002	uM
1-[2-[4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0003	uM
1-[2-[5-fluoro-4-(5-fluoropyrimidin-2-yl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0003	uM
1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-4-carbonitrile	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0003	uM
methyl 1-[2-[[5-(4-tert-butylphenyl)-1,3,4-thiadiazol-2-yl]amino]phenyl]-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-4-carboxylate	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0003	uM
1-[2-(4-chloro-7-hydroxy-3,3-dimethyl-2H-indol-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0004	uM
1-[2-[4-(2-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0004	uM
[(1S,2R,3S,4R,5S)-4-(6-amino-2-methylsulfanylpurin-9-yl)-2,3-dihydroxy-1-bicyclo[3.1.0]hexanyl]methyl phosphono hydrogen phosphate	1930049: Agonist activity at human P2Y1R in human 1321N1 cells	ec50	0.0004	uM
1-[2-[1’-(2,2-dimethylpropyl)-4-fluoro-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1151495: Antagonist activity at P2Y1 receptor in human platelets by FLIPR assay in presence of 2-methylthio-ADP	ic50	0.0004	uM
[(1S,2R,3S,4R,5R)-4-(6-amino-2-methylsulfanylpurin-9-yl)-2,3-dihydroxy-1-bicyclo[3.1.0]hexanyl]methyl phosphono hydrogen phosphate	150330: Accumulation of inositol phosphate in 1321N1 astrocytoma cells expressing human P2Y1 purinoceptor	ec50	0.0004	uM
1-[2-(7-hydroxy-3,3-dimethyl-4-phenyl-2H-indol-1-yl)phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0004	uM
1-[2-[6-fluoro-4-(4-fluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0004	uM
1-[2-[4-(2,6-difluoro-4-pyridinyl)-5-fluoro-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0005	uM
1-[2-[5-fluoro-7-hydroxy-3,3-dimethyl-4-[6-(trifluoromethyl)-3-pyridinyl]-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0005	uM
1-[2-[4-(2,4-difluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0005	uM
1-[2-[5-fluoro-7-hydroxy-3,3-dimethyl-4-[5-(trifluoromethyl)-2-pyridinyl]-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0006	uM
4-chloro-1’-(2,2-dimethylpropyl)-1-[2-[[5-[4-(trifluoromethoxy)phenyl]-1,3,4-thiadiazol-2-yl]amino]phenyl]spiro[2H-indole-3,4’-piperidine]-7-ol	1141862: Inhibition of P2Y1 receptor in human washed platelets assessed as decrease in 2-methylthio-ADP-induced calcium signal transduction pathway activation by FLIPR assay	ic50	0.0006	uM
1-[2-[4-(3,5-difluorophenyl)-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0006	uM
[(1R,2S,4S,5S)-4-[2-iodo-6-(methylamino)purin-9-yl]-2-phosphonooxy-1-bicyclo[3.1.0]hexanyl]methyl dihydrogen phosphate	1421250: Displacement of [3H]2-chloro-N 6- methyl-( N )-methanocarba-2’-deoxyadenosine 3 ’ ,5 ‘-bis-phosphate from human P2Y1 expressed in baculovirus infected insect Sf9 cells after 30 mins by scintillation spectrometric method	ki	0.0008	uM
1-[2-[4-(4-chlorophenyl)-5-fluoro-7-hydroxy-3,3-dimethyl-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0011	uM
[(2R,3S,4R,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	240294: Effective concentration required for the activation of wild-type P2Y1 receptors expressed in COS-7 cells for the accumulation of inositol phosphate	ec50	0.0013	uM
1-[2-[7-hydroxy-3,3-dimethyl-4-[4-(trifluoromethyl)phenyl]-2H-indol-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1179943: Antagonist activity at P2Y1 receptor in washed human platelets assessed as 1 uM 2-methylthio-ADP-induced calcium flux by FLIPR assay	ic50	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aspirin	affects response to substance, decreases response to substance	3
Adenosine Triphosphate	decreases response to substance, increases reaction, affects binding, increases activity, increases abundance (+1 more)	2
Calcium	affects binding, increases abundance, increases activity, affects reaction, increases phosphorylation (+1 more)	2
Nickel	increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
methylthio-ADP	affects binding, increases activity	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sodium arsenite	affects expression	1
butyraldehyde	increases expression	1
3’-O-(4-benzoyl)benzoyladenosine 5’-triphosphate	decreases reaction, increases reaction, increases secretion	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	increases expression	1
avobenzone	decreases expression	1
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	increases activity, increases phosphorylation, decreases reaction	1
bisindolylmaleimide I	decreases reaction, increases activity, increases phosphorylation	1
N(6)-methyl-2’-deoxyadenosine 3’,5’-diphosphate	decreases response to substance, increases reaction, affects binding, decreases activity, decreases reaction	1
AG 1879	decreases reaction, increases activity, increases phosphorylation	1
tyrphostin AG 1024	decreases reaction, increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-chloro-N6-methyl-(N)-methanocarba-2’-deoxyadenosine-3’,5’-bisphosphate	decreases activity	1
bisindolylmaleimide IX	decreases reaction, increases activity, increases phosphorylation	1
dorsomorphin	affects cotreatment, increases expression	1
asparanin A	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Estradiol	affects cotreatment, decreases expression	1

ChEMBL screening assays

234 unique, capped per target: 121 binding, 113 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1067692	Functional	Agonist activity at G-protein coupled P2Y1 receptor expressed in human 1321N1 cells assessed as increase in calcium by Fura2 assay	A novel insulin secretagogue based on a dinucleoside polyphosphate scaffold. — *J Med Chem*
CHEMBL1070722	Binding	Inhibition of P2Y1 at 10 uM	Part II: piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8RY	Ubigene HCT 116 P2RY1 KO	Cancer cell line	Male
CVCL_D9M3	Ubigene HEK293 P2RY1 KO	Transformed cell line	Female
CVCL_H355	1321N1/P2Y1	Cancer cell line	Male
CVCL_KU48	1321N1 P2RY1 Gq	Cancer cell line	Male
CVCL_LB05	PathHunter U2OS P2RY1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_LB06	PathHunter U2OS P2RY1 beta-arrestin	Cancer cell line	Female
CVCL_ZD90	1321N1-HA-P2Y1	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for P2RY1 across ~30M SureChEMBL compounds — explore on Sugi Predict.