P2RY12

Summary

P2RY12 (purinergic receptor P2Y12, HGNC:18124) is a protein-coding gene on chromosome 3q25.1, encoding P2Y purinoceptor 12 (Q9H244). Receptor for ADP and ATP coupled to G proteins that inhibit the adenylyl cyclase second messenger system.

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 is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 64805 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet-type bleeding disorder 8 (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 20 total — 4 likely-pathogenic
• GTEx eGene: eQTL in 34 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 8
• Drug target: yes — 10 curated mechanism-of-action drugs; 11 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 7 — Cangrelor, Cangrelor Tetrasodium, Clopidogrel Besilate, +4 more
• Constraint (gnomAD): pLI 0.08 (LoF-tolerant), LOEUF 1.16 (unconstrained)
• MANE Select transcript: NM_022788
• Interaction hub: 1,714 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18124
Approved symbol	P2RY12
Name	purinergic receptor P2Y12
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	P2Y12, SP1999, HORK3
Ensembl gene	ENSG00000169313
Ensembl biotype	protein_coding
OMIM	600515
Entrez	64805

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

MANE Select: ENST00000302632

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000302632, ENST00000468596, ENST00000955805, ENST00000955806, ENST00000955807, ENST00001139839

RefSeq mRNA: 2 — MANE Select: NM_022788 NM_022788, NM_176876

CCDS: CCDS3159

Canonical transcript exons

ENST00000302632 — 3 exons

Exon	Start	End
ENSE00001157311	151336843	151338859
ENSE00001169257	151340596	151340760
ENSE00001813621	151384692	151384753

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 97.12.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0864 / max 331.6989, expressed in 240 samples.

Highest expression (Bgee): inferior vagus X ganglion, superior vestibular nucleus, ventral tegmental area, subthalamic nucleus, medulla oblongata.

Genetic regulation across tissues (GTEx eQTL / sQTL)

P2RY12 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 34 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	1.1e-51	-0.33	3:151383958:C:T
Adipose Subcutaneous	eqtl	1.9e-44	-0.46	3:151379603:G:A
Lung	eqtl	2.9e-41	-0.44	3:151387443:A:G
Adipose Visceral Omentum	eqtl	1.4e-30	-0.42	3:151383903:C:T
Artery Tibial	eqtl	5.3e-23	-0.41	3:151383958:C:T
Esophagus Muscularis	eqtl	4.6e-22	-0.36	3:151387443:A:G
Heart Atrial Appendage	eqtl	7.1e-22	-0.40	3:151387443:A:G
Esophagus Gastroesophageal Junction	eqtl	4.9e-21	-0.40	3:151384664:A:G
Artery Aorta	eqtl	3.2e-20	-0.32	3:151387443:A:G
Spleen	eqtl	8.6e-19	-0.44	3:151399774:C:A
Breast Mammary Tissue	eqtl	9.0e-19	-0.36	3:151383570:T:G
Thyroid	eqtl	7.9e-18	-0.31	3:151384664:A:G
Esophagus Mucosa	eqtl	2.5e-16	-0.37	3:151387443:A:G
Colon Sigmoid	eqtl	1.5e-15	-0.36	3:151383903:C:T
Adrenal Gland	eqtl	5.1e-15	-0.45	3:151383903:C:T
Artery Coronary	eqtl	2.0e-14	-0.44	3:151387443:A:G
Skin Sun Exposed Lower leg	eqtl	6.4e-14	-0.32	3:151387443:A:G
Colon Transverse	eqtl	3.0e-12	-0.29	3:151399774:C:A
Stomach	eqtl	3.2e-10	-0.29	3:151387443:A:G
Whole Blood	eqtl	4.0e-10	-0.17	3:151387443:A:G

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
45161	1.9173	233
45152	0.7420	86
45154	0.1138	52
45153	0.0927	54
45151	0.0773	42
45150	0.0675	37
45157	0.0288	1
45155	0.0149	1
202983	0.0134	5
45158	0.0094	1

Top tissues by expression

showing 100 of 249 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	97.12	gold quality
superior vestibular nucleus	UBERON:0007227	96.60	gold quality
ventral tegmental area	UBERON:0002691	94.74	gold quality
subthalamic nucleus	UBERON:0001906	93.92	gold quality
medulla oblongata	UBERON:0001896	92.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.45	gold quality
monocyte	CL:0000576	90.55	gold quality
corpus callosum	UBERON:0002336	89.35	gold quality
dorsal root ganglion	UBERON:0000044	89.32	gold quality
leukocyte	CL:0000738	89.22	gold quality
midbrain	UBERON:0001891	88.67	gold quality
spinal cord	UBERON:0002240	88.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.10	gold quality
substantia nigra	UBERON:0002038	87.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.68	gold quality
trigeminal ganglion	UBERON:0001675	87.66	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.40	gold quality
prefrontal cortex	UBERON:0000451	84.69	gold quality
amygdala	UBERON:0001876	81.85	gold quality
temporal lobe	UBERON:0001871	81.19	gold quality
epithelial cell of pancreas	CL:0000083	80.99	silver quality
entorhinal cortex	UBERON:0002728	80.69	gold quality
substantia nigra pars compacta	UBERON:0001965	80.65	gold quality
pons	UBERON:0000988	80.48	gold quality
Ammon’s horn	UBERON:0001954	80.16	gold quality
hypothalamus	UBERON:0001898	79.95	gold quality
caudate nucleus	UBERON:0001873	79.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.19	gold quality
medial globus pallidus	UBERON:0002477	78.76	gold quality
putamen	UBERON:0001874	78.48	gold quality
nucleus accumbens	UBERON:0001882	78.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.24	gold quality
cerebral cortex	UBERON:0000956	78.17	gold quality
frontal cortex	UBERON:0001870	77.48	gold quality
globus pallidus	UBERON:0001875	77.46	gold quality
anterior cingulate cortex	UBERON:0009835	77.19	gold quality
neocortex	UBERON:0001950	76.86	gold quality
parietal lobe	UBERON:0001872	75.84	gold quality
forebrain	UBERON:0001890	75.79	gold quality
ganglionic eminence	UBERON:0004023	75.14	gold quality
postcentral gyrus	UBERON:0002581	74.69	gold quality
brain	UBERON:0000955	74.35	gold quality
lymph node	UBERON:0000029	73.86	gold quality
superior frontal gyrus	UBERON:0002661	73.63	gold quality
endothelial cell	CL:0000115	72.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.91	gold quality
lateral globus pallidus	UBERON:0002476	72.79	gold quality
cortical plate	UBERON:0005343	72.30	gold quality
calcaneal tendon	UBERON:0003701	71.99	gold quality
occipital lobe	UBERON:0002021	71.85	gold quality
tibial nerve	UBERON:0001323	71.77	gold quality
ventricular zone	UBERON:0003053	71.72	gold quality
smooth muscle tissue	UBERON:0001135	69.63	gold quality
adipose tissue	UBERON:0001013	69.17	gold quality
granulocyte	CL:0000094	68.50	gold quality
thoracic mammary gland	UBERON:0005200	67.91	gold quality
vermiform appendix	UBERON:0001154	67.59	gold quality
mammary gland	UBERON:0001911	67.44	gold quality
right frontal lobe	UBERON:0002810	67.30	gold quality
right coronary artery	UBERON:0001625	67.17	gold quality
lower lobe of lung	UBERON:0008949	67.10	gold quality
adrenal tissue	UBERON:0018303	66.91	gold quality
primary visual cortex	UBERON:0002436	66.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	66.71	gold quality
spleen	UBERON:0002106	66.37	gold quality
gall bladder	UBERON:0002110	66.35	gold quality
rectum	UBERON:0001052	66.16	gold quality
bone marrow cell	CL:0002092	65.30	silver quality
right lung	UBERON:0002167	64.88	gold quality
adipose tissue of abdominal region	UBERON:0007808	64.10	gold quality
superficial temporal artery	UBERON:0001614	63.95	gold quality
mammary duct	UBERON:0001765	63.86	gold quality
epithelium of mammary gland	UBERON:0003244	63.81	gold quality
omental fat pad	UBERON:0010414	63.68	gold quality
blood	UBERON:0000178	63.64	gold quality
peritoneum	UBERON:0002358	63.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	62.92	gold quality
pancreatic ductal cell	CL:0002079	62.85	silver quality
left coronary artery	UBERON:0001626	62.71	gold quality
coronary artery	UBERON:0001621	62.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	61.89	gold quality
caecum	UBERON:0001153	61.67	gold quality
palpebral conjunctiva	UBERON:0001812	61.26	gold quality
descending thoracic aorta	UBERON:0002345	61.11	gold quality
germinal epithelium of ovary	UBERON:0001304	61.10	gold quality
colonic epithelium	UBERON:0000397	61.04	silver quality
lower esophagus muscularis layer	UBERON:0035833	60.52	gold quality
lower esophagus	UBERON:0013473	60.49	gold quality
lung	UBERON:0002048	60.32	gold quality
parietal pleura	UBERON:0002400	60.11	gold quality
tonsil	UBERON:0002372	60.03	gold quality
tendon	UBERON:0000043	60.00	gold quality
sural nerve	UBERON:0015488	59.71	silver quality
adrenal gland	UBERON:0002369	59.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	59.51	gold quality
left adrenal gland cortex	UBERON:0035825	59.21	gold quality
upper lobe of lung	UBERON:0008948	59.12	gold quality
left adrenal gland	UBERON:0001234	58.94	gold quality
upper lobe of left lung	UBERON:0008952	58.85	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	781.01
E-GEOD-100618	yes	118.58
E-HCAD-35	yes	32.50
E-HCAD-25	yes	15.76
E-HCAD-30	no	932.44
E-ANND-3	no	2.17

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	122.3
Frontal cortex	tissue	104.3
Hypothalamus	tissue	76.3
Periaqueductal gray	tissue	72.9
Septum	tissue	71.0
Pons	tissue	65.5
Substantia nigra	tissue	58.8
Amygdala	tissue	52.3
Corpus callosum	tissue	51.1
Midbrain	tissue	50.1
Ventral forebrain	tissue	48.8
Putamen	tissue	48.6
Medulla oblongata	tissue	47.7
Thalamus	tissue	45.8
Spinal cord	tissue	43.9
Hippocampal formation	tissue	42.9
Basal ganglia	tissue	36.6	medium
Superior colliculi	tissue	35.7
Cerebral cortex	tissue	33.2	medium
Insular cortex	tissue	33.2
Entorhinal cortex	tissue	32.2
Motor cortex	tissue	31.6
Prefrontal cortex	tissue	31.5
Temporal cortex	tissue	30.3
Retrosplenial cortex	tissue	28.0
Retrosplenial and cingulate cortex	tissue	27.2
Occipital cortex	tissue	24.4
Somatosensory cortex	tissue	20.9
Olfactory bulb	tissue	19.8
Hippocampus	tissue	13.9	medium
Locus coeruleus	tissue	11.7
Nucleus accumbens	tissue	11.5
Lymph node	tissue	9.2	low
Tonsil	tissue	8.1	low
Adipose tissue	tissue	8.0	not detected
Choroid plexus	tissue	6.9
Cerebellum	tissue	6.0	high
Spleen	tissue	5.1	low
Postcentral gyrus	tissue	4.4
Adrenal gland	tissue	3.8	not detected
Breast	tissue	3.5	not detected
Salivary gland	tissue	2.7	not detected
Small intestine	tissue	2.6	not detected
Fallopian tube	tissue	2.4	low
Lung	tissue	2.3	not detected
Liver	tissue	2.3	not detected
Placenta	tissue	2.2	high
Gallbladder	tissue	2.0	not detected
Seminal vesicle	tissue	1.9	not detected
Appendix	tissue	1.8	not detected
Parathyroid gland	tissue	1.5	not detected
Smooth muscle	tissue	1.5	not detected
Colon	tissue	1.5	not detected
Rectum	tissue	1.3	not detected
Cervix	tissue	1.2	not detected
Heart muscle	tissue	1.2	not detected
Esophagus	tissue	1.1	not detected
Urinary bladder	tissue	1.1	not detected
Duodenum	tissue	1.1	not detected
Stomach 1	tissue	1.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (51.1), Ventral spinal cord (43.9), Subiculum (42.9), Dorsal spinal cord (42.1), Dorsal hippocampus (39.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting P2RY12 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 71 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-5002-5P	99.76	70.84	1763

Functional genomics

gnomAD constraint: pLI 0.0827, LOEUF 1.16, missense Z 1.26 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000302632 — one region, missense o/e 0.87.

Literature-anchored findings (GeneRIF, showing 40)

• Characterization and channel coupling of the nucleotide receptor in brain capillary endothelial cells (PMID:12080041)
• identification of the reactive cysteine residues on the human P2Y(12) receptor by site-directed mutagenesis using pCMBS as the thiol reagent (PMID:12560222)
• PI3-K activation is signaled by rapid feedback amplification that involves P2Y(12) receptor-mediated activation of Syk. (PMID:12606772)
• 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)
• Intercellular calcium communication is primarily mediated by a signaling mchanism operating between this protein, ITGA2B and ITGB3. (PMID:12668663)
• In healthy subjects ADP-induced platelet aggregation is associated with a haplotype of the P2Y12 receptor gene. Carriers of the H2 haplotype may have an increased risk of atherothrombosis and less response to platelet inhibitors (PMID:12912815)
• Supports P2Y(12) as a drug target compared with P2Y(1). (PMID:14644082)
• ADP-mediated P2Y1 and P2Y12 receptor activation supports LPA-induced platelet aggregation. (PMID:14645014)
• The P2Y12 H2 haplotype is associated with atherosclerosis. (PMID:14662702)
• stimulation of the human P2Y12 receptor stably expressed in Chinese hamster ovary cells activates two major intracellular signaling mechanisms leading either to cell proliferation or to actin cytoskeleton reorganization (PMID:14717977)
• Whereas P2RY1 antagonism did not affect collagen or thrombin-induced thrombin generation, P2RY12 antagonism did decrease both, suggesting that ADP potentiates thrombin generation primarily through the P2Y12 receptor (PMID:15099288)
• GIRK channels are important functional effectors of the P2Y(12) receptor in human platelets. (PMID:15142872)
• the Src family kinase inhibitor PP1 selectively potentiates the contribution to the calcium response by P2Y(12), although inhibition of adenylate cyclase by P2Y(12) is unaffected (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)
• platelet ADP receptor P2Y(12) and clusterin are downregulated in patients with systemic lupus erythematosus (PMID:15304052)
• Results describe the cloning of DNA sequences encoding the murine ortholog of the human P2Y12 receptor, and its expression in the mouse brain. (PMID:15464998)
• P2Y12 receptors could play a key role in the hypersensitivity of platelets in type 2 diabetic patients. (PMID:15483100)
• Absence of desensitization of the Gi protein-coupled P2Y12 receptor-dependent responses could represent a mechanism to preserve the hemostatic properties in platelets (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)
• Galpha(i) signaling downstream of P2Y12 activation, but not Galpha(q) or Galpha(z) signaling downstream of P2Y1 or alpha2A activation, respectively, has a requirement for lipid rafts that is necessary for its function in ADP-mediated platelet activation (PMID:15869601)
• P2Y12 ADP receptor has a role in tyrosine phosphorylation of proteins of 27 and 31 kDa in thrombin-stimulated human platelets (PMID:15886804)
• a P2Y12 34C>T polymorphism may have a role in development of ischemic cerebrovascular events in patients with peripheral artery disease (PMID:15933261)
• function in the platelet procoagulant response (PMID:15968399)
• There is no association between P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease. (PMID:16181985)
• Identification of 5-phosphoribosyl 1-pyrophosphate and leukotriene E4 as P2Y12 receptor agonists. (PMID:16185654)
• Results suggest that P2Y12 plays a potentiatory role in ADP-induced shape change through regulation of the Rho kinase pathway. (PMID:16236603)
• 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)
• Data show that at relatively high concentration of agonist, inhibition of the P2Y12 receptor and of calcium mobilization result in complete inhibition of PAR4-induced aggregation, with no effect on either thrombin or PAR1-mediated platelet aggregation. (PMID:16837456)
• Outside-in signaling via P2Y12 and both PI3Kbeta and PI3Kgamma isoforms is required for maintenance of a platelet aggregate. (PMID:16840732)
• No influence of the T744C polymorphism of the P2Y12 receptor gene on clopidogrel response in acute coronary syndrome (PMID:17337040)
• the haplotype H2 of purinergic receptor P2Y G-protein coupled 12 (P2RY12) was significantly associated with a lower risk of incident Deep vein thrombosis/pulmonary embolism as compared to the reference haplotype H1 (PMID:17707382)
• Gene sequence variations of the P2Y12 receptor gene are associated with the presence of significant coronary artery disease, particularly in non-smoking individuals (PMID:17803810)
• common variation in the P2Y12 gene predicts restenosis in percutaneous coronary intervention-treated patients (PMID:18175333)
• The P2Y(13) Met-158-Thr polymorphism is in tight linkage disequilibrium with the P2Y(12) locus but is not associated with acute myocardial infaction or classical cardiovascular risk factors (PMID:18213371)
• Use VerifyNow P2Y12 assay to measure platelet P2Y12 receptor blockade by prasugrel and clopidogrel. (PMID:18278193)
• Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation (PMID:18577829)
• present data clearly show that P2Y purinoceptor 11 and P2Y purinoceptor 12 are expressed in human pancreatic islets (PMID:18726826)
• the the G(i)-coupled P2Y12 receptor has a role in the regulation of diacylglycerol-mediated events in activated platelets (PMID:18755689)
• plays a critical role in the regulation of integrin alphaIIb beta3 functions. (review) (PMID:18800613)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	p2ry12	ENSDARG00000069945
mus_musculus	P2ry12	ENSMUSG00000036353
rattus_norvegicus	P2ry12	ENSRNOG00000013902

Paralogs (6): GPR87 (ENSG00000138271), PTAFR (ENSG00000169403), GPR34 (ENSG00000171659), P2RY14 (ENSG00000174944), GPR171 (ENSG00000174946), P2RY13 (ENSG00000181631)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1918089) 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 platelet physiology	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
Pan troglodytes	P60019	100.0%	Diamond
Pan paniscus	Q3SAG9	100.0%	Diamond
Gorilla gorilla gorilla	Q6XCF2	100.0%	Diamond
Cricetulus griseus	P58825	98.8%	Diamond
Macaca fascicularis	Q95KC3	98.0%	Diamond
Meriones unguiculatus	Q99PE4	93.6%	Diamond
Bos taurus	Q3ZBK9	93.1%	Diamond
Sus scrofa	Q9XSD4	86.5%	Diamond
Cavia porcellus	P21556	86.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
AADACL2-AS1	ncRNA	101928142
LINC02066	ncRNA	105374158
MED12L	protein-coding	116931
IGSF10	protein-coding	285313
AADACL2	protein-coding	344752
MIR5186	ncRNA	100847036
P2RY13	protein-coding	53829
CLRN1-AS1	ncRNA	116933
GPR171	protein-coding	29909
GPR87	protein-coding	53836
CLRN1	protein-coding	7401
P2RY14	protein-coding	9934

Protein

Protein identifiers

P2Y purinoceptor 12 — Q9H244 (reviewed: Q9H244)

Alternative names: ADP-glucose receptor, P2T(AC), P2Y(AC), P2Y(cyc), P2Y12 platelet ADP receptor, SP1999

All UniProt accessions (1): Q9H244

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for ADP and ATP coupled to G proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in the platelets, lower levels in the brain. Lowest levels in the lung, appendix, pituitary and adrenal gland. Expressed in the spinal cord and in the fetal brain.

Disease relevance. Bleeding disorder, platelet-type, 8 (BDPLT8) [MIM:609821] A condition characterized by mild to moderate mucocutaneous bleeding, and excessive bleeding after surgery or trauma. The defect is due to severe impairment of platelet response to ADP resulting in defective platelet aggregation. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The transmembrane domain is composed of seven transmembrane helices; most of these are not strictly perpendicular to the plane of the membrane, but are tilted and/or kinked. Agonist binding promotes a conformation change in the extracellular loops that leads to an inward movement of the transmembrane helices. Antagonists such as AZD1283 can bind to an overlapping site, but block the inward movement of the transmembrane helices.

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

RefSeq proteins (2): NP_073625, NP_795345 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR005394	P2Y12_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (65 total): helix 16, binding site 10, mutagenesis site 9, topological domain 8, transmembrane region 7, sequence variant 4, modified residue 2, glycosylation site 2, disulfide bond 2, chain 1, region of interest 1, compositionally biased region 1, strand 1, turn 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
4PXZ	Crystal structure of P2Y12 receptor in complex with 2MeSADP	X-RAY DIFFRACTION	2.5
4NTJ	Structure of the human P2Y12 receptor in complex with an antithrombotic drug	X-RAY DIFFRACTION	2.62
7PP1	Crystal structure of the P2Y12 receptor in complex with the inverse agonist selatogrel.	X-RAY DIFFRACTION	2.78
7XXI	Cryo-EM structure of the purinergic receptor P2Y12R in complex with 2MeSADP and Gi	ELECTRON MICROSCOPY	3
4PY0	Crystal structure of P2Y12 receptor in complex with 2MeSATP	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H244-F1	85.11	0.59

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, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

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 (10)

Position	Role
93	ADP
97	ADP
105	ADP
156–159	ADP
175–179	ADP
187	ADP
191	ADP
256–259	ADP
263	ADP
280	ADP

Post-translational modifications (2)

Type	Positions
Phosphoserine	55, 57

Disulfide bonds (2)

Type	Positions
Disulfide bond	17–270, 97–175

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	6, 13

Mutagenesis-validated functional residues (9)

Position	Phenotype
80	abolishes adp binding.
83	no effect on adp binding.
97	abolishes adp binding.
156	slightly decreases affinity for adp.
159	slightly decreases affinity for adp.
175	abolishes adp binding.
256	decreases affinity for adp.
280	abolishes adp binding.
281	abolishes adp binding.

Function

Pathways and Gene Ontology

Reactome pathways

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

12 pathways:

ID	Pathway	Evidence
R-HSA-392170	ADP signalling through P2Y purinoceptor 12	curated
R-HSA-418594	G alpha (i) signalling events	curated
R-HSA-417957	P2Y receptors	curated
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: 256 (showing top): GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, GOBP_MYELOID_LEUKOCYTE_MIGRATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, REACTOME_P2Y_RECEPTORS, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_FOREBRAIN_DEVELOPMENT

GO Biological Process (26): substrate-dependent cell migration, cell extension (GO:0006930), 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), hemostasis (GO:0007599), calcium-mediated signaling (GO:0019722), cerebral cortex radial glia-guided migration (GO:0021801), cell projection organization (GO:0030030), lamellipodium assembly (GO:0030032), platelet activation (GO:0030168), positive regulation of integrin activation by cell surface receptor linked signal transduction (GO:0033626), positive regulation of cell adhesion mediated by integrin (GO:0033630), response to axon injury (GO:0048678), regulation of chemotaxis (GO:0050920), positive regulation of chemotaxis (GO:0050921), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), platelet aggregation (GO:0070527), cellular response to ATP (GO:0071318), visual system development (GO:0150063), positive regulation of ruffle assembly (GO:1900029), regulation of microglial cell migration (GO:1904139), positive regulation of microglial cell migration (GO:1904141), G protein-coupled adenosine receptor signaling pathway (GO:0001973), signal transduction (GO:0007165), blood coagulation (GO:0007596), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589)

GO Molecular Function (5): G protein-coupled adenosine receptor activity (GO:0001609), G protein-coupled ADP receptor activity (GO:0001621), guanyl-nucleotide exchange factor activity (GO:0005085), G protein-coupled purinergic nucleotide receptor activity (GO:0045028), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (5): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), cell projection membrane (GO:0031253), cell body membrane (GO:0044298)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by GPCR	2
Signal amplification	1
Nucleotide-like (purinergic) receptors	1
GPCR downstream signalling	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

57 GO namespaces:

Category	Terms
G protein-coupled receptor activity	3
cellular anatomical structure	3
plasma membrane bounded cell projection assembly	2
G protein-coupled receptor signaling pathway	2
chemotaxis	2
substrate-dependent cell migration	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
regulation of body fluid levels	1
intracellular signaling cassette	1
cerebral cortex radially oriented cell migration	1
telencephalon glial cell migration	1
cellular component organization	1
lamellipodium organization	1
cell activation	1
blood coagulation	1
cell surface receptor signaling pathway	1
integrin activation	1
positive regulation of integrin activation	1
cell adhesion mediated by integrin	1
regulation of cell adhesion mediated by integrin	1
positive regulation of cell adhesion	1
response to wounding	1
regulation of response to external stimulus	1
regulation of locomotion	1
positive regulation of response to external stimulus	1
positive regulation of locomotion	1
regulation of chemotaxis	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
platelet activation	1
homotypic cell-cell adhesion	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
sensory system development	1
ruffle assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of ruffle assembly	1
G protein-coupled adenosine receptor signaling pathway	1
ADP binding	1
G protein-coupled purinergic nucleotide receptor activity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
purinergic nucleotide receptor activity	1
G protein-coupled purinergic nucleotide receptor signaling pathway	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
plasma membrane region	1
plasma membrane bounded cell projection	1
plasma membrane	1
cell body	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 36 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	BP	mutant phenotype
platelet aggregation	BP	mutant phenotype
cell surface	CC	high-throughput assay
membrane	CC	direct assay
G protein-coupled ADP receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,714 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RY12	P2RX1	P51575	973
P2RY12	TMEM119	Q4V9L6	900
P2RY12	CYP2C19	P33259	887
P2RY12	TREM2	Q9NZC2	815
P2RY12	SALL1	Q9NSC2	778
P2RY12	OLFML3	Q9NRN5	750
P2RY12	AIF1	P55008	747
P2RY12	CSF1R	P07333	741
P2RY12	PPIG	Q13427	733
P2RY12	APOE	P02649	732
P2RY12	CST7	O76096	731
P2RY12	CD68	P34810	720
P2RY12	GP6	Q9HCN6	719
P2RY12	ITGA2B	P08514	718
P2RY12	TYROBP	O43914	717

IntAct

Human interaction partners of P2RY12 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
GPR89A	association	0.350	2

BioGRID (137 interactions; top human partners by supporting records): ATP5B (Affinity Capture-MS; 3 records), ATP5F1 (Affinity Capture-MS; 3 records), C19orf25 (Affinity Capture-MS; 3 records), CAV1 (Affinity Capture-MS; 3 records), CERS5 (Affinity Capture-MS; 3 records), CERS6 (Affinity Capture-MS; 3 records), CRELD1 (Affinity Capture-MS; 3 records), EBP (Affinity Capture-MS; 3 records), ECSIT (Affinity Capture-MS; 3 records), GEMIN8 (Affinity Capture-MS; 3 records), GOLGA5 (Affinity Capture-MS; 3 records), GOLPH3 (Affinity Capture-MS; 3 records), GPR89A (Affinity Capture-MS; 3 records), ITPR2 (Affinity Capture-MS; 3 records), KIAA2013 (Affinity Capture-MS; 3 records)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
P2RY12	“up-regulates activity”	GNAI1	binding
P2RY12	“up-regulates activity”	GNAI3	binding
P2RY12	“up-regulates activity”	GNAO1	binding
P2RY12	“up-regulates activity”	GNAZ	binding
ADP	“up-regulates activity”	P2RY12	“chemical activation”

Protein complexes (CORUM) (2)

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

2 complexes by size:

Complex	Subunits	Members
★ F2RL3-P2RY12 cpmplex	2	F2RL3, P2RY12
★ P2Y purinoceptor 12	1	P2RY12

Disease & clinical

Genetic variants

Variant evidence for P2RY12: 20 ClinVar records (4 pathogenic / likely pathogenic); 8 PharmGKB clinical annotations; 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	8
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2572656	NM_022788.5(P2RY12):c.662dup (p.Arg222fs)	Likely pathogenic	criteria provided, single submitter	1
3361598	NM_001393769.1(MED12L):c.4354_4355insG (p.Leu1452fs)	Likely pathogenic	criteria provided, single submitter	1
4529923	NM_001393769.1(MED12L):c.2394_2395del (p.Val800fs)	Likely pathogenic	criteria provided, single submitter	1
3391828	GRCh37/hg19 3q24-25.1(chr3:146504503-151662391)x1	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore P2RY12’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 140):

Position(s)	Effect	Δscore	Sites
3:151338860–151338861	acceptor_loss	1.0000	4
3:151340594–151340595	donor_loss	1.0000	5
3:151338869	acceptor_gain	0.9900
3:151340761–151340762	acceptor_loss	0.9900	6
3:151340771	acceptor_gain	0.9900
3:151384690–151384691	donor_loss	0.9900	4
3:151338861	acceptor_loss	0.9800
3:151384691	donor_loss	0.9800
3:151338861	acceptor_loss	0.9700
3:151384690	donor_loss	0.9600

AlphaMissense

851 missense substitutions predicted likely pathogenic (of 2,264 scored), across 222 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
D70	8	0.983	0.995
F198	8	0.976	0.997
D294	8	0.972	0.988
H253	8	0.965	0.995
H187	8	0.964	0.984
F249	8	0.939	0.997
F305	8	0.920	0.993
N65	8	0.870	0.994
F114	8	0.868	0.945
D121	8	0.853	0.933
D84	8	0.824	0.897
C97	7	0.992	0.997
C175	7	0.988	0.996
F252	7	0.969	0.991
F104	7	0.963	0.987
F62	7	0.954	0.975
W149	7	0.953	0.998
F245	7	0.949	0.990
N43	7	0.935	0.986
K179	7	0.926	0.996

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Glioblastoma Multiforme)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	0.000184

Disease associations

OMIM: gene MIM:600515 | disease phenotypes: MIM:609821

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
platelet-type bleeding disorder 8	Strong	Autosomal recessive	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
platelet-type bleeding disorder 8	Definitive	AR
platelet-type bleeding disorder 8	Moderate	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Bleeding and platelet disorders	green
Inherited bleeding disorders	green

Mondo (1): platelet-type bleeding disorder 8 (MONDO:0012354)

Orphanet (1): Bleeding disorder due to P2Y12 defect (Orphanet:36355)

HPO phenotypes

8 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000421	Epistaxis
HP:0000978	Bruising susceptibility
HP:0001892	Abnormal bleeding
HP:0001934	Persistent bleeding after trauma
HP:0004846	Prolonged bleeding after surgery
HP:0004866	Impaired ADP-induced platelet aggregation
HP:0031364	Ecchymosis

GWAS associations

1 associations:

Study	Trait	p-value
GCST006479_25	Diverticular disease	9e-11

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009959	diverticular disease

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C565220	Bleeding Disorder Due To P2RY12 Defect *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2001 (SINGLE PROTEIN), CHEMBL4524011 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the P2RY12 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.

10 curated-mechanism drugs:

Drug	Modality	Max phase
CANGRELOR	Small molecule	4
CANGRELOR TETRASODIUM	Small molecule	4
CLOPIDOGREL BESILATE	Small molecule	4
CLOPIDOGREL BISULFATE	Small molecule	4
PRASUGREL BESYLATE	Small molecule	4
TICAGRELOR	Small molecule	4
TICLOPIDINE HYDROCHLORIDE	Small molecule	4
SELATOGREL	Small molecule	3
ELINOGREL	Small molecule	2
REGRELOR DISODIUM	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 71,019 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL334966	CANGRELOR	4	942
CHEMBL1097279	CANGRELOR TETRASODIUM	4	115
CHEMBL1771	CLOPIDOGREL	4	40,706
CHEMBL1201772	PRASUGREL	4	856
CHEMBL398435	TICAGRELOR	4	3,116
CHEMBL760	ANAGRELIDE	4	24,027
CHEMBL4297589	SELATOGREL	3	56
CHEMBL2103828	ELINOGREL	2	281
CHEMBL1162175	REGRELOR	2	10
CHEMBL261244	REGRELOR DISODIUM	2	3
CHEMBL69139	LIXAZINONE	2	907

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs2046934	Efficacy	3	clopidogrel	Major Adverse Cardiac Events (MACE)
rs3732759	Efficacy	3	clopidogrel	Coronary Disease
rs6787801	Efficacy	3	clopidogrel
rs6787801	Efficacy	3	cangrelor
rs6809699	Efficacy	3	clopidogrel	Coronary Artery Disease
rs9859552	Efficacy	3	cangrelor
rs2046934	Efficacy	4	clopidogrel	Acute coronary syndrome;Angina Pectoris
rs6785930	Efficacy,Toxicity	4	clopidogrel

PharmGKB variants

6 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2046934	MED12L, P2RY12	3	1.75	2	clopidogrel
rs6785930	MED12L, P2RY12	4	-2.25	1	clopidogrel
rs6787801	MED12L, P2RY12	3	2.50	2	cangrelor;clopidogrel
rs6809699	MED12L, P2RY12	3	2.25	1	clopidogrel
rs9859552	MED12L, P2RY12	3	0.50	1	cangrelor
rs3732759	MED12L, P2RY12	3	2.00	1	clopidogrel

PharmGKB variant annotations

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

32 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs6787801	cangrelor	Other	Allele G is associated with 5% lower ADP-induced peak platelet aggregation in-vitro when exposed to cangrelor as compared to genotype AA.	PMID:20126830
rs2046934	clopidogrel	Efficacy	Genotypes AG + GG are associated with increased likelihood of platelet aggregation inhibition when treated with clopidogrel in people with Coronary Disease as compared to genotype AA.	PMID:25730082
rs2046934	clopidogrel	Efficacy	Allele A is associated with increased risk of major adverse cardiac events (mace) when treated with clopidogrel as compared to allele G.	PMID:26870959
rs2046934	clopidogrel	Efficacy	Genotype AA is associated with increased response to clopidogrel in people with Coronary Disease as compared to genotypes AG + GG.	PMID:27566695
rs3732759	clopidogrel	Efficacy	Genotype GG is associated with decreased response to clopidogrel in people with Coronary Disease as compared to genotypes AA + AG.	PMID:27566695
rs2046934	aspirin, clopidogrel	Efficacy	Genotypes AG + GG are associated with increased platelet reactivity when treated with aspirin and clopidogrel as compared to genotype AA.	PMID:28255319
rs2046934	aspirin, clopidogrel	Toxicity	Genotypes AG + GG are associated with increased risk of major adverse cardiac events (mace) when treated with aspirin and clopidogrel as compared to genotype AA.	PMID:28255319
rs2046934	clopidogrel	Toxicity	Genotype GG is associated with increased likelihood of Acute coronary syndrome when treated with clopidogrel as compared to genotypes AA + AG.	PMID:28261502
rs6785930	clopidogrel	Toxicity	Genotypes AA + AG is associated with increased risk of adverse events when treated with clopidogrel as compared to genotype GG.	PMID:28383427
rs6785930	clopidogrel	Efficacy	Genotypes AA + AG is associated with increased resistance to clopidogrel as compared to genotype GG.	PMID:28383427
rs6809699	clopidogrel	Toxicity	Genotypes AA + AC is associated with increased risk of adverse events when treated with clopidogrel as compared to genotype CC.	PMID:28383427
rs6809699	clopidogrel	Efficacy	Genotypes AA + AC is associated with increased resistance to clopidogrel as compared to genotype CC.	PMID:28383427
rs6787801	clopidogrel	Efficacy	Allele G is associated with decreased residual on-clopidogrel platelet reactivity when treated with clopidogrel in people with Coronary Artery Disease as compared to allele A.	PMID:20031628
rs6801273	clopidogrel	Efficacy	Allele T is associated with decreased residual on-clopidogrel platelet reactivity when treated with clopidogrel in people with Coronary Artery Disease as compared to allele C.	PMID:20031628
rs10935838	clopidogrel	Efficacy	Genotype AG is associated with decreased platelet aggregation when exposed to clopidogrel in healthy individuals as compared to genotype GG.	PMID:27756942
rs2046934	clopidogrel	Efficacy	Genotype AG is associated with decreased platelet aggregation when exposed to clopidogrel in healthy individuals as compared to genotype AA.	PMID:27756942
rs5853517	clopidogrel	Efficacy	Genotype T/del is associated with decreased platelet aggregation when exposed to clopidogrel in healthy individuals as compared to genotype del/del.	PMID:27756942
rs6809699	clopidogrel	Efficacy	Genotype AC is associated with decreased platelet aggregation when exposed to clopidogrel in healthy individuals as compared to genotype CC.	PMID:27756942
rs6809699	clopidogrel	Efficacy	Genotypes AA + AC is associated with increased resistance to clopidogrel in people with Coronary Disease as compared to genotype CC.	PMID:36581799
rs6785930	clopidogrel	Efficacy	Genotypes AA + AG is associated with increased likelihood of Drug Resistance when treated with clopidogrel in people with Coronary Disease as compared to genotype GG.	PMID:39927599
rs6809699	clopidogrel	Efficacy	Genotypes AA + AC is associated with increased likelihood of high on-treatment platelet reactivity when treated with clopidogrel in people with Acute coronary syndrome or Coronary Disease as compared to genotype CC.	PMID:41028360
rs2046934			Allele G is associated with increased risk of Coronary Artery Disease as compared to allele A.	PMID:17803810
rs2046934		Other	Allele G is associated with increased risk of Peripheral Vascular Diseases as compared to allele A.	PMID:14662702
rs2046934		Other	Allele G is associated with increased platelet aggregation.	PMID:12912815
rs6809699	clopidogrel	Efficacy	Genotype AA is associated with stronger aggreagtion when treated with clopidogrel in people with Coronary Artery Disease as compared to genotypes AC + CC.	PMID:18485500
rs6809699	clopidogrel	Efficacy	Genotype AA is associated with increased risk of non-response when treated with clopidogrel in people with Coronary Artery Disease as compared to genotypes AC + CC.	PMID:18485500
rs6809699	clopidogrel	Efficacy	Genotype AA is associated with increased risk of clopidogrel resistance when treated with clopidogrel in people with Coronary Artery Disease as compared to genotypes AC + CC.	PMID:18485500
rs9859552	cangrelor	Other	Genotype TT is associated with 20% and 17% less inhibition of platelet aggregation with crangrelor (0.05 and 0.25 microM) in-vitro when exposed to cangrelor as compared to genotype GG.	PMID:20126830
rs2046934	clopidogrel	Efficacy	Genotypes AG + GG are associated with increased platelet activation response to ADP when treated with clopidogrel in people with Acute coronary syndrome as compared to genotype AA.	PMID:23751603
rs2046934	clopidogrel	Other	Genotypes AG + GG are associated with decreased platelet function when treated with clopidogrel in people with Acute coronary syndrome as compared to genotype AA.	PMID:18577829
rs6785930	clopidogrel	Efficacy	Allele A is associated with increased risk of neurological events when treated with clopidogrel in people with Peripheral Vascular Diseases as compared to genotype GG.	PMID:15933261
rs6787801	clopidogrel	Efficacy	Genotypes AG + GG are associated with high on-treatment platelet reactivity in CYP2C19*1/*1 carriers when treated with clopidogrel in patients undergoing percutaneous coronary intervention as compared to genotype AA.	PMID:21831410

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — P2Y receptors

Most potent curated ligand interactions (29 total), top 25:

Ligand	Action	Affinity	Parameter
[3H]2MeSADP	Full agonist	9.6	pIC50
2MeSADP	Full agonist	9.2	pKi
selatogrel	Antagonist	8.7	pKd
ADPβS	Full agonist	8.6	pIC50
[3H]AZ12464237	Antagonist	8.5	pKd
[3H]PSB-0413	Antagonist	8.5	pKd
[3H]PSB-22219	Antagonist	8.34	pKd
PSB-22219	Antagonist	8.3	pKi
AR-C67085	Antagonist	8.2	pKd
compound 20o [PMID: 22984835]	Antagonist	8.1	pKi
cangrelor	Antagonist	8.0	pIC50
AZD1283	Antagonist	8.0	pKi
regrelor	Antagonist	7.95	pIC50
ARL66096	Antagonist	7.95	pIC50
ticagrelor	Antagonist	7.85	pKi
PSB-0702	Antagonist	7.7	pIC50
PSB-0739	Antagonist	7.6	pKi
BX 667	Antagonist	7.0	pIC50
clopidogrel (active metabolite)	Antagonist	6.9	pKi
compound 4 [PMID: 22984835]	Antagonist	6.9	pKi
compound 4 [PMID: 23083103]	Antagonist	6.9	pIC50
compound 58l [PMID: 30843696]	Antagonist	6.53	pIC50
BX 048	Antagonist	6.5	pIC50
INS49266	Antagonist	6.28	pIC50
Ap4A	Antagonist	6.0	pIC50

Binding affinities (BindingDB)

1152 measured of 1243 human assays (1276 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
CHEMBL5181634	KI	0.3 nM
CHEMBL251024	IC50	0.32 nM
CHEMBL5176593	IC50	0.33 nM
CHEMBL437204	IC50	0.5 nM
(S)-4-(4-(4-(ethylcarbamoyl)piperidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	0.58 nM
(S)-4-(4-(3-carbamoylazetidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	0.64 nM
{Cyclohexyl-[4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]quinolin-7-yloxy)-butyryl]-amino}-acetic acid methyl ester	EC50	0.7 nM
cangrelor	IC50	0.7 nM
(S)-5-(4-(butoxycarbonyl)piperazin-1-yl)-5-oxo-4-(4-(4-((2-oxopyrrolidin-1-yl)methyl)piperidin-1-yl)-6-phenylpicolinamido)pentanoic acid	KI	0.79 nM
CHEMBL1160364	IC50	0.794 nM
CHEMBL2172149	KI	0.8 nM
CHEMBL3326907	IC50	0.9 nM
(S)-4-(4-(4-(dimethylcarbamoyl)piperidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	0.98 nM
5-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]quinolin-7-yloxy)-pentanoic acid cycloheptyl-methyl-amide	EC50	1 nM
CHEMBL3288123	IC50	1 nM
(4S)-4-[({4-[3-(Dimethylamino)propyl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic Acid	KI	1 nM
CHEMBL5179719	IC50	1 nM
CHEMBL5184268	IC50	1 nM
CHEMBL5195237	IC50	1 nM
CHEMBL5173489	IC50	1 nM
CHEMBL5192953	IC50	1 nM
CHEMBL5203416	IC50	1 nM
(S)-5-(4-(butoxycarbonyl)piperazin-1-yl)-4-(4-(4-(diethylcarbamoyl)piperidin-1-yl)-6-phenylpicolinamido)-5-oxopentanoic acid	KI	1.1 nM
(S)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)-4-(6-phenyl-4-(4-(pyrrolidin-1-ylmethyl)piperidin-1-yl)picolinamido)pentanoic acid	KI	1.1 nM
(S)-4-(4-(4-(azetidine-1-carbonyl)piperidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	1.2 nM
(4S)4-[({4-[(1-Acetylpiperidin-4-yl)ethoxy]-6-phenylpyridin-2-yl}carbonyl)mino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic Acid	KI	1.3 nM
(4S)4-{[(4-{[1-(Ethoxycarbonyl)piperidin-4-yl]methoxy}-6-phenylpyridin-2-yl)carbonyl]amino}-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic Acid	KI	1.3 nM
(S)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)-4-(6-phenyl-4-((R)-3-(pyrrolidine-1-carbonyl)pyrrolidin-1-yl)picolinamido)pentanoic acid	KI	1.4 nM
(4S)5-Oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}-4-({[6-phenyl-4-({[(piperidin-4-ylmethyl)amino]carbonyl}amino)pyridin-2-yl]carbonyl}amino)pentanoic acid	KI	1.4 nM
(4S)4-{[(4-{[(2-Methoxyethoxy)carbonyl]amino}-6-phenylpyridin-2-yl)carbonyl]amino}-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid	KI	1.4 nM
(4S)5-[4-(Butoxycarbonyl)piperazin-1-yl]-5-oxo-4-[({6-phenyl-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]pyridin-2-yl}carbonyl)amino]pentanoic Acid	KI	1.5 nM
(S)-4-(4-(4-((ethylamino)methyl)piperidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	1.5 nM
(4S)4-{[(4-{4-[(Methylamino)ethyl]piperidin-1-yl}-6-phenylpyridin-2-yl)carbonyl]amino}-5-oxo-5-{4-[(pentyloxy)carbonyl]-piperazin-1-yl}pentanoic Acid	KI	1.5 nM
(4S)5-[4-(Butoxycarbonyl)iperazin-1-yl]-4-({[4-({[methyl-(tetrahydro-2H-pyran-4-ylmethyl)mino]carbonyl}oxy)6-phenylpyridin-2-yl]carbonyl}amino)5-oxopentanoic Acid	KI	1.5 nM
(4S)5-[4-(Butoxycarbonyl)piperazin-1-yl]-4-({[4-({[(3R)3-methoxypyrrolidin-1-yl]carbonyl}oxy)6-phenylpyridin-2-yl]carbonyl}-amino)5-oxopentanoic Acid	KI	1.5 nM
CHEMBL2172129	KI	1.5 nM
Selatogrel	KD	1.5 nM
(S)-4-(4-(3-(methylcarbamoyl)azetidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	1.7 nM
(S)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)-4-(6-phenyl-4-((S)-3-(pyrrolidine-1-carbonyl)pyrrolidin-1-yl)picolinamido)pentanoic acid	KI	1.7 nM
(S)-4-(4-((S)-3-(diethylcarbamoyl)pyrrolidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	1.7 nM
(S)-4-(4-(4-(2-amino-2-oxoethyl)piperazin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	1.7 nM
(4S)5-Oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}-4-{[(6-phenyl-4-{[(piperidin-4-ylmethoxy)carbonyl]amino}pyridin-2-yl)carbonyl]amino}pentanoic acid	KI	1.7 nM
(4S)5-[4-(Butoxycarbonyl)piperazin-1-yl]-4-[({4-[(morpholin-4-ylcarbonyl)xy]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxopentanoic Acid	KI	1.7 nM
(4S)-4-[({4-[(4-Acetylpiperazin-1-yl)carbonyl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic Acid	KI	1.7 nM
(4S)5-[4-(Butoxycarbonyl)piperazin-1-yl]-4-({[4-({[methyl-(tetrahydrofuran-3-yl)mino]carbonyl}oxy)6-phenylpyridin-2-yl]carbonyl}amino)5-oxopentanoic Acid	KI	1.8 nM
(4S)4-{[(4-{4-[(Dimethylamino)ethyl]piperidin-1-yl}-6-phenylpyridin-2-yl)carbonyl]amino}-5-oxo-5-{4-[(pentyloxy)carbonyl]-piperazin-1-yl}pentanoic Acid	KI	1.9 nM
(4S)4-{[(4-{[(3-Aminopropoxy)carbonyl]amino}-6-phenylpyridin-2-yl)carbonyl]amino}-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid	KI	1.9 nM
CHEMBL3798413	IC50	2 nM
(S)-4-(4-(3-(ethylcarbamoyl)azetidin-1-yl)-6-phenylpicolinamido)-5-oxo-5-(4-(pentyloxycarbonyl)piperazin-1-yl)pentanoic acid	KI	2 nM

ChEMBL bioactivities

1610 potent at pChembl≥5 of 1726 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	Kd	0.1585	nM	CHEMBL455536
9.60	Ki	0.2512	nM	CHEMBL251041
9.52	Ki	0.3	nM	CHEMBL5181634
9.50	IC50	0.3162	nM	CHEMBL251024
9.48	IC50	0.33	nM	CHEMBL5176593
9.42	Ki	0.38	nM	CHEMBL570295
9.40	IC50	0.3981	nM	CANGRELOR
9.40	IC50	0.4	nM	CANGRELOR
9.40	Ki	0.4	nM	CHEMBL567915
9.35	IC50	0.45	nM	CANGRELOR
9.34	Ki	0.46	nM	CHEMBL567561
9.30	IC50	0.5012	nM	CHEMBL437204
9.24	Ki	0.58	nM	CHEMBL601696
9.22	Ki	0.6	nM	CHEMBL567740
9.21	Ki	0.61	nM	CHEMBL565974
9.20	Ki	0.631	nM	CHEMBL249790
9.19	Ki	0.64	nM	CHEMBL601489
9.17	Ki	0.67	nM	CHEMBL565836
9.17	Ki	0.68	nM	CHEMBL570295
9.16	Ki	0.69	nM	CHEMBL568059
9.15	EC50	0.7	nM	CHEMBL90804
9.15	Ki	0.7	nM	CHEMBL567133
9.15	Ki	0.71	nM	CHEMBL567709
9.15	IC50	0.7	nM	CANGRELOR TETRASODIUM
9.10	Ki	0.8	nM	CHEMBL2172149
9.10	IC50	0.7943	nM	CHEMBL1160364
9.10	Ki	0.79	nM	CHEMBL568211
9.10	Ki	0.79	nM	CHEMBL601695
9.08	Ki	0.83	nM	CHEMBL566913
9.05	IC50	0.9	nM	CHEMBL3326907
9.05	Ki	0.9	nM	CHEMBL565409
9.04	Ki	0.92	nM	CHEMBL571599
9.01	Ki	0.98	nM	CHEMBL601698
9.00	EC50	1	nM	CHEMBL431799
9.00	EC50	1	nM	CHEMBL90237
9.00	IC50	1	nM	CHEMBL3288123
9.00	IC50	1	nM	CHEMBL5179719
9.00	IC50	1	nM	CHEMBL5184268
9.00	IC50	1	nM	CHEMBL5195237
9.00	IC50	1	nM	CHEMBL5173489
9.00	IC50	1	nM	CHEMBL5192953
9.00	IC50	1	nM	CHEMBL5203416
9.00	Ki	0.99	nM	CHEMBL570275
9.00	Ki	1	nM	CHEMBL569914
9.00	Ki	1	nM	CHEMBL569097
8.96	Ki	1.1	nM	CHEMBL601903
8.96	Ki	1.1	nM	CHEMBL601692
8.92	Ki	1.2	nM	CHEMBL567416
8.92	Ki	1.2	nM	CHEMBL570128
8.92	Ki	1.2	nM	CHEMBL566745

PubChem BioAssay actives

1596 with measured affinity, of 2368 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
disodium;1-amino-4-(4-anilino-3-sulfonatoanilino)-9,10-dioxoanthracene-2-sulfonate	1443659: Competitive antagonist activity at human P2Y12 receptor expressed in CHO cells assessed as forskolin/ 2-methylthio-ADP-induced cAMP production preincubated for 10 mins followed 2-methylthio-ADP addition measured after 3.5 hrs by luciferase reporter gene assay	kd	0.0002	uM
(1S,2R,3S,4R)-2,3-dihydroxy-4-[7-[[(1R,2S)-2-phenylcyclopropyl]amino]-5-propylsulfanyltriazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1-carboxylic acid	309606: Displacement of [125I] labeled ligand from human P2Y12 receptor in human platelets	ki	0.0003	uM
ethyl 5-cyano-2-methyl-6-[4-(3-phenyl-1H-1,2,4-triazol-5-yl)piperidin-1-yl]pyridine-3-carboxylate	1871493: Inhibition of 2-MeS-ADP induced P2Y12 (unknown origin) signalling expressed in CHO cells membrane incubated for 45 mins by 35S-GTPgammaS assay	ic50	0.0003	uM
(2S)-2-[[(E)-3-[(2R,3S,4R,5R)-5-[7-(butylamino)-5-propylsulfanyltriazolo[4,5-d]pyrimidin-3-yl]-3,4-dihydroxyoxolan-2-yl]prop-2-enoyl]amino]butanedioic acid	1953760: Antagonist activity at human P2Y12 by aggregation assay	ic50	0.0003	uM
2-(2-fluoroethoxy)-6-propyl-4-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]thieno[2,3-d]pyrimidine	1850678: Displacement of [3H]-2MesADP from human P2Y12 in HEK cell membrane assessed as inhibition constant incubated for 1 hr by scintillation counter method	ki	0.0003	uM
(4S)-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)-4-[[2-phenyl-6-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]pyrimidine-4-carbonyl]amino]pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0004	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-4-[[4-[4-(ethylcarbamoyl)piperidin-1-yl]-6-phenylpyridine-2-carbonyl]amino]-5-oxopentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0004	uM
Cangrelor	1298771: Antagonist activity at P2Y12 receptor in human platelets assessed as inhibition of ADP-induced platelet aggregation by turbidimetric method	ic50	0.0004	uM
(2S)-2-[[(E)-3-[(1R,2R,3S,4R)-4-[7-(butylamino)-5-propylsulfanyltriazolo[4,5-d]pyrimidin-3-yl]-2,3-dihydroxycyclopentyl]prop-2-enoyl]amino]butanedioic acid	1953760: Antagonist activity at human P2Y12 by aggregation assay	ic50	0.0005	uM
(4S)-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)-4-[[2-phenyl-6-[4-(pyrrolidine-1-carbonyl)piperidin-1-yl]pyrimidine-4-carbonyl]amino]pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0005	uM
(1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino]-5-(3,3,3-trifluoropropylsulfanyl)triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol	309606: Displacement of [125I] labeled ligand from human P2Y12 receptor in human platelets	ki	0.0006	uM
(4S)-4-[[6-[4-(diethylaminomethyl)piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0006	uM
(4S)-4-[[6-[4-(ethylcarbamoyl)piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0006	uM
(4S)-4-[[4-[4-(ethylcarbamoyl)piperidin-1-yl]-6-phenylpyridine-2-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	457976: Inhibition of human P2Y12 receptor expressed in CHO cells	ki	0.0006	uM
(4S)-4-[[4-(3-carbamoylazetidin-1-yl)-6-phenylpyridine-2-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	457976: Inhibition of human P2Y12 receptor expressed in CHO cells	ki	0.0006	uM
tetrasodium;[dichloro(phosphonato)methyl]-[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2-methylsulfanylethylamino)-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]oxolan-2-yl]methoxy-oxidophosphoryl]oxyphosphinate	480267: Antagonist activity at P2Y12 receptor by [35S]GTPgammaS binding assay	ic50	0.0007	uM
methyl 2-[cyclohexyl-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]amino]acetate	92528: Inhibition of platelet aggregation using adenosine diphosphate (ADP) as activating agent in human platelet rich plasma (PRP)	ec50	0.0007	uM
(4S)-4-[[6-(4-aminopiperidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0007	uM
(4S)-4-[[6-[4-(2-hydroxyethoxy)piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0007	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-5-oxo-4-[[2-phenyl-6-[4-(pyrrolidine-1-carbonyl)piperidin-1-yl]pyrimidine-4-carbonyl]amino]pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0007	uM
(4S)-4-[[6-[4-[2-(ethylamino)-2-oxoethyl]piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0007	uM
[dichloro-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2,2,2-trifluoroethylamino)-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methyl]phosphonic acid	1298771: Antagonist activity at P2Y12 receptor in human platelets assessed as inhibition of ADP-induced platelet aggregation by turbidimetric method	ic50	0.0008	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-4-[[5-[2-[(2S)-2-(cyclobutylcarbamoyl)pyrrolidin-1-yl]-2-oxoethoxy]-1-phenylpyrazole-3-carbonyl]amino]-5-oxopentanoic acid	703441: Displacement of [33P]2-MeS-ADP from human recombinant P2Y12 receptor expressed in CHO cell membranes by scintillation counting method	ki	0.0008	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-4-[[6-[4-(diethylcarbamoyl)piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxopentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0008	uM
(4S)-4-[[6-[4-(azetidine-1-carbonyl)piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0008	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-5-oxo-4-[[4-[4-[(2-oxopyrrolidin-1-yl)methyl]piperidin-1-yl]-6-phenylpyridine-2-carbonyl]amino]pentanoic acid	457976: Inhibition of human P2Y12 receptor expressed in CHO cells	ki	0.0008	uM
(4S)-4-[[6-[4-[2-(methylamino)-2-oxoethyl]piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0009	uM
(4S)-4-[[6-[4-[2-(azetidin-1-yl)-2-oxoethyl]piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0009	uM
2-[3-[[4-(4-butanoyl-5-methylpyrazol-1-yl)phenyl]carbamoyl]-5-methylindol-1-yl]acetic acid	1186074: Displacement of [33P]2MeS-ADP from P2Y12 receptor (unknown origin) transfected in CHO cells after 30 mins by scintillation counting analysis	ic50	0.0009	uM
N-cyclohexyl-N-methyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanamide	92528: Inhibition of platelet aggregation using adenosine diphosphate (ADP) as activating agent in human platelet rich plasma (PRP)	ec50	0.0010	uM
N-cycloheptyl-N-methyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanamide	92528: Inhibition of platelet aggregation using adenosine diphosphate (ADP) as activating agent in human platelet rich plasma (PRP)	ec50	0.0010	uM
1-(5-butanoyl-3-cyano-6-methylsulfanyl-2-pyridinyl)-N-(1-phenylcyclopropyl)sulfonylpiperidine-4-carboxamide	1153640: Antagonist activity P2Y12 receptor in human washed platelets assessed as inhibition of ADP-induced platelet aggregation after 5 to 90 mins by spectrophotometric analysis	ic50	0.0010	uM
(4S)-4-[[4-[3-(dimethylamino)propyl]-6-phenylpyridine-2-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	461227: Displacement of [33P]ADP from human recombinant P2Y12 receptor expressed in CHO cells	ki	0.0010	uM
(4S)-4-[(6-morpholin-4-yl-2-phenylpyrimidine-4-carbonyl)amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0010	uM
(4S)-5-oxo-4-[[6-[4-[(2-oxopyrrolidin-1-yl)methyl]piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0010	uM
(4S)-4-[[4-[4-(dimethylcarbamoyl)piperidin-1-yl]-6-phenylpyridine-2-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	457976: Inhibition of human P2Y12 receptor expressed in CHO cells	ki	0.0010	uM
[4-[(2S)-3-(4-butoxycarbonylpiperazin-1-yl)-3-oxo-2-[(2-phenyl-1,3-thiazole-4-carbonyl)amino]propyl]phenyl]phosphonic acid	1871489: Displacement of tritium-labeled 2MeSADP from human P2Y12 expressed in CHO cells measured after 2 hrs by scintillation counting method	ic50	0.0010	uM
[(2R)-3-(4-butoxycarbonylpiperazin-1-yl)-2-[[5-(4-methylpiperazin-1-yl)-2-phenyl-1,3-thiazole-4-carbonyl]amino]-3-oxopropyl]phosphonic acid	1871489: Displacement of tritium-labeled 2MeSADP from human P2Y12 expressed in CHO cells measured after 2 hrs by scintillation counting method	ic50	0.0010	uM
[(2R)-3-(4-butoxycarbonylpiperazin-1-yl)-2-[[5-[butyl(methyl)amino]-2-phenyl-1,3-thiazole-4-carbonyl]amino]-3-oxopropyl]phosphonic acid	1871489: Displacement of tritium-labeled 2MeSADP from human P2Y12 expressed in CHO cells measured after 2 hrs by scintillation counting method	ic50	0.0010	uM
[(2R)-3-(4-butoxycarbonylpiperazin-1-yl)-3-oxo-2-[(2-phenyl-1,3-thiazole-4-carbonyl)amino]propyl]phosphonic acid	1871489: Displacement of tritium-labeled 2MeSADP from human P2Y12 expressed in CHO cells measured after 2 hrs by scintillation counting method	ic50	0.0010	uM
[4-[(2S)-3-(4-ethoxycarbonylpiperazin-1-yl)-3-oxo-2-[(2-phenyl-1,3-thiazole-4-carbonyl)amino]propyl]phenyl]phosphonic acid	1871489: Displacement of tritium-labeled 2MeSADP from human P2Y12 expressed in CHO cells measured after 2 hrs by scintillation counting method	ic50	0.0010	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-4-[[5-[(3S)-3-methoxypyrrolidin-1-yl]-2-phenyl-1,3-thiazole-4-carbonyl]amino]-5-oxopentanoic acid	1871489: Displacement of tritium-labeled 2MeSADP from human P2Y12 expressed in CHO cells measured after 2 hrs by scintillation counting method	ic50	0.0010	uM
(4S)-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)-4-[[6-phenyl-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]pyridine-2-carbonyl]amino]pentanoic acid	457976: Inhibition of human P2Y12 receptor expressed in CHO cells	ki	0.0011	uM
(4S)-5-(4-butoxycarbonylpiperazin-1-yl)-4-[[4-[4-(diethylcarbamoyl)piperidin-1-yl]-6-phenylpyridine-2-carbonyl]amino]-5-oxopentanoic acid	457976: Inhibition of human P2Y12 receptor expressed in CHO cells	ki	0.0011	uM
(4S)-4-[[6-(2-methoxyethoxy)-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0012	uM
(4S)-4-[[4-(2-methoxyethoxy)-6-phenylpyrimidine-2-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0012	uM
(4S)-4-[[6-(2-methoxyethylamino)-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0012	uM
(4S)-4-[[6-(3-ethoxyazetidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0012	uM
(4S)-4-[[6-(4-carbamoylpiperazin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0012	uM
(4S)-4-[[6-[4-(methylaminomethyl)piperidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxo-5-(4-pentoxycarbonylpiperazin-1-yl)pentanoic acid	443858: Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	ki	0.0012	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Clopidogrel	decreases activity, affects response to substance, affects reaction, affects binding	6
cangrelor	decreases phosphorylation, affects response to substance, affects binding, decreases abundance, decreases activity	3
Adenosine Diphosphate	affects response to substance, affects reaction, increases expression	3
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
phosphatidylinositol 3,4,5-triphosphate	affects binding, decreases abundance, decreases activity	1
CGP 52608	affects binding, increases reaction	1
CT 50547	affects binding, decreases activity	1
Ticagrelor	decreases activity, affects binding	1
Anthraquinones	decreases activity	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

160 unique, capped per target: 102 binding, 58 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042521	Binding	Binding affinity at human recombinant P2Y12 receptor expressed in CHO cells by radioligand binding assay	Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation. — *Bioorg Med Chem Lett*
CHEMBL1042522	Functional	Antagonist activity at P2Y12 receptor in human platelet rich plasma assessed as inhibition of ADP-induced platelet aggregation by light transmission aggregometry	Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Y1	Abcam A-549 P2RY12 KO	Cancer cell line	Male
CVCL_D2NT	Abcam THP-1 P2RY12 KO	Cancer cell line	Male
CVCL_H357	1321N1/P2Y12/Galpha15	Cancer cell line	Male
CVCL_KY75	PathHunter CHO-K1 P2RY12 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB07	PathHunter U2OS P2RY12 Total GPCR Internalization	Cancer cell line	Female
CVCL_ZD95	1321N1-HA-P2Y12	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 P2RY12 across ~30M SureChEMBL compounds — explore on Sugi Predict.