F2R

Summary

F2R (coagulation factor II thrombin receptor, HGNC:3537) is a protein-coding gene on chromosome 5q13.3, encoding Proteinase-activated receptor 1 (P25116). High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores.

Coagulation factor II receptor is a 7-transmembrane receptor involved in the regulation of thrombotic response. Proteolytic cleavage leads to the activation of the receptor. F2R is a G-protein coupled receptor family member. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2149 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 54 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001992

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3537
Approved symbol	F2R
Name	coagulation factor II thrombin receptor
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Aliases	TR, CF2R, PAR1, PAR-1
Ensembl gene	ENSG00000181104
Ensembl biotype	protein_coding
OMIM	187930
Entrez	2149

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000319211, ENST00000505600

RefSeq mRNA: 2 — MANE Select: NM_001992 NM_001311313, NM_001992

CCDS: CCDS4032

Canonical transcript exons

ENST00000319211 — 2 exons

Exon	Start	End
ENSE00001259490	76732314	76735770
ENSE00001259499	76716126	76716395

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 97.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.9356 / max 637.3052, expressed in 1562 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57143	45.0054	1554
57148	0.5816	376
57147	0.3267	170
57145	0.3223	192
57146	0.2808	142
57144	0.2623	130
57149	0.1566	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.29	gold quality
ventricular zone	UBERON:0003053	95.61	gold quality
decidua	UBERON:0002450	95.22	gold quality
ganglionic eminence	UBERON:0004023	94.75	gold quality
right lung	UBERON:0002167	94.08	gold quality
gall bladder	UBERON:0002110	93.18	gold quality
skin of hip	UBERON:0001554	92.78	gold quality
right coronary artery	UBERON:0001625	92.61	gold quality
lower lobe of lung	UBERON:0008949	92.59	gold quality
descending thoracic aorta	UBERON:0002345	92.18	gold quality
upper leg skin	UBERON:0004262	92.05	gold quality
thoracic aorta	UBERON:0001515	91.65	gold quality
ascending aorta	UBERON:0001496	91.53	gold quality
aorta	UBERON:0000947	89.48	gold quality
cortical plate	UBERON:0005343	89.33	gold quality
skin of abdomen	UBERON:0001416	89.27	gold quality
skin of leg	UBERON:0001511	88.68	gold quality
minor salivary gland	UBERON:0001830	88.65	gold quality
embryo	UBERON:0000922	88.60	gold quality
zone of skin	UBERON:0000014	88.52	gold quality
spleen	UBERON:0002106	88.18	gold quality
tibial artery	UBERON:0007610	88.00	gold quality
popliteal artery	UBERON:0002250	87.99	gold quality
adrenal tissue	UBERON:0018303	87.92	gold quality
calcaneal tendon	UBERON:0003701	87.85	gold quality
smooth muscle tissue	UBERON:0001135	87.75	gold quality
left coronary artery	UBERON:0001626	87.56	gold quality
jejunal mucosa	UBERON:0000399	87.24	gold quality
granulocyte	CL:0000094	86.98	gold quality
upper lobe of lung	UBERON:0008948	86.91	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	665.08
E-HCAD-10	yes	41.44
E-CURD-112	yes	37.73
E-HCAD-9	yes	17.14
E-MTAB-9067	yes	11.88
E-MTAB-5061	yes	11.03
E-ANND-3	yes	7.47
E-GEOD-83139	yes	7.40
E-MTAB-8205	no	364.01

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
CD44	Activation
CORO1C	Activation
FOSL1	Activation
KLF6	Activation
RAB3A	Activation
SDC4	Activation
THBS1	Activation
TNFRSF12A	Activation

Upstream regulators (CollecTRI, top): AP1, AR, EGR1, JUN, NFATC1, PAX8, RARA, SP1, SP3, STAT3, TFAP2A, TP53, TWIST1, TWIST2

miRNA regulators (miRDB)

113 targeting F2R, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583

Literature-anchored findings (GeneRIF, showing 40)

• Though PAR1 is insufficient to induce metastasis in cells with low TF expression, it enhances the metastatic potential of cells with high TF expression, indicating a possible synergy between TF and PAR1 in promoting metastasis. (PMID:11816709)
• Proteolytic activation of PAR1 is required for thrombin stimulation and the control of angiogenic processes in tissue repair. (PMID:11888681)
• When expressed in respiratory epithelial cells and cell lines, protease-activated receptor 1 (PAR1)induces the release of IL-6, IL-8, and PGE2. (PMID:11907122)
• PAR-1 is upregulated in pancreatic cancer (PMID:11964083)
• CLL B cells consistently express thrombin receptor mRNA; co-expression of angiogenic molecules and receptors suggest autocrine pathways of stimulation. (PMID:11986954)
• Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis. Review. (PMID:12023853)
• a novel role for Go proteins in the signal transduction of thrombin receptors in HMECs (human microvascular endothelial cells) that regulates calcium signaling (PMID:12039967)
• target for endothelial cell protein C receptor (EPCR)-dependent activated protein C(APC) signaling, suggesting a role for this receptor cascade in protection from sepsis (PMID:12052963)
• down-regulation is controlled by sorting nexin 1 (PMID:12058063)
• These data suggest that an untranslated RNA plays a role in PAR-1 gene expression during embryonic growth. (PMID:12084570)
• Both PAR1 and PAR2 upregulate COX-2, but not COX-1, expression in HUVEC cells (PMID:12195707)
• PAR1-mediated proinflammatory cytokine release from respiratory epithelial cells in vitro is inhibited by pretreatment with house dust mite allergen Der p 1. (PMID:12370395)
• stimulation of PAR-1 or PAR-2 on HUR leads to iPLA(2)-catalyzed phospholipid hydrolysis, resulting in the production of metabolites that may mediate inflammation or provide cytoprotection to the bladder. (PMID:12372769)
• The number of PAR-1 receptors on the platelet surface is associated with the intervening sequence IVSn-14 A/T intronic variation, and it was also found to govern the platelet response to the SFLLRN agonist in terms of aggregation & P-selectin expression. (PMID:12406873)
• Thrombin upregulates COX-2-derived prostaglandin E2 synthesis by both catalytic cleavage of PAR1 and bFGF-dependent noncatalytic activity (PMID:12505789)
• PAR1 is a primary mediator of RhoA activation, signaling, and cytoskeletal reorganization when expressed on LNCaP prostate cancer cells. (PMID:12534282)
• data suggest that activated protein C regulates calcium concentration in human brain endothelium and in human umbilical vein endothelial cells by binding to endothelial protein C receptor and signaling via protease activated receptor-1 (PMID:12586611)
• Activation and up-regulation of PAR1 is tightly coupled to brain inflammation and neuronal damage during HIV-1 infection. (PMID:12594292)
• Review. PAR1 expression correlates with the invasion properties of breast carcinoma. Part of the molecular mechanism of PAR1 invasion involves the formation of focal contact complexes on PAR1 activation. (PMID:12637343)
• the aberrant expression of the functional thrombin receptor PAR-1 in colon cancers and its important involvement in cell proliferation and motility (PMID:12707033)
• gastric epithelial cells express thrombin receptors and that these receptors may play a protective role in the gastric mucosa. (PMID:12737439)
• This review focuses on the role of the thrombin receptor in melanoma and its regulation by AP-2. (PMID:12789289)
• differentiation of human monocytes is associated with differential expression of functionally active PARs that mediate distinct regulatory functions in inflammation and atherogenesis. (PMID:12805069)
• PAR1 could be clearly detected on the surface of eosinophils, however thrombin had no effect on eosinophil function (PMID:12832443)
• PAR-1 mediates the proliferation-modulating effects of thrombin on prostate cancer cells. (PMID:12883880)
• analysis of the PAR-1 promoter regions bp -365 to -329 and bp -206 to -180 demonstrated that Sp1 was predominantly bound to the PAR-1 promoter in metastatic cells, whereas AP-2 was bound to the PAR-1 promoter in nonmetastatic cells. (PMID:12975361)
• Our data suggest that thrombin/PAR-1 may inhibit Sp1-dependent HCMV replication, which might be an important regulatory mechanism for HCMV persistence and replication in RPE (PMID:13680213)
• PAR1 is the predominant thrombin receptor on invasive extravillous trophoblasts;findings support a role for PAR1, and potentially PAR2 and PAR3 in the invasive phase of human placentation (PMID:14507634)
• PAR-1 and PAR-4 have roles in activating GPIb translocation into the cytoskeleton in platelets (PMID:14521606)
• PAR-1 signaling, along with thrombin, has a role in up-regulating the synthesis of TFPI-2 via a MAPK/COX-2-dependent pathway (PMID:14623891)
• PAR-1 mRNA was expressed specifically in the mesenchymal portions, including dermal papilla and connective tissue sheath, of anagen hair follicles. (PMID:14632180)
• thrombin disarms PAR-1 from further proteolytic activation, but leaves the receptor responsive for non-tethered ligands (PMID:14642534)
• stroke patients exhibited significant cleavage and internalization of PAR-1 and failed to respond to thrombin in vitro, indicating that high concentrations of thrombin occur with acute cerebrovascular ischemic events in vivo (PMID:14961162)
• Results reveal that a novel alteration in trafficking of activated protease-activated receptor 1 causes persistent signaling, and may contribute to breast carcinoma cell invasion. (PMID:14966279)
• the information that specifies PAR1 shedding resides within its N-terminal exodomain rather than its heptahelical segment; and ADAM17/TACE or a metalloproteinase with similar properties mediates PAR1 shedding (PMID:14982936)
• internalization of activated PAR1 is controlled by multiple regulatory mechanisms involving phosphorylation and a highly conserved tyrosine-based motif, YXXL (PMID:15023990)
• evidence that only one of the thrombin platelet receptors, PAR1 or PAR4, is sufficient to induce intracellular signaling leading to the cleavage of the beta3 cytoplasmic domain (PMID:15045135)
• PAR-1 and PAR-4 signal Rap1B activation, the ability of thrombin to activate this GTPase independently of secreted ADP involves costimulation of both receptors as well as binding to GPIb-IX-V. (PMID:15078882)
• results suggest stimulation of both the PAR1 & PAR4 receptors are necessary for thrombin-induced procoagulant activity, & the P2Y(12) receptor, but not the P2Y(1) receptor, is responsible for potentiation of agonist-induced platelet procoagulant activity (PMID:15099288)
• The inactivation of PAR1 due to proteolytic removal of the ligand region may contribute to the termination of the intracellular signaling initiated by thrombin in the vascular endothelial cells. (PMID:15183114)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	F2R	ENSDARG00000059507
danio_rerio	f2r	ENSDARG00000060012
danio_rerio	f2r2.1	ENSDARG00000077638
danio_rerio	f2r2.2	ENSDARG00000086236
danio_rerio	F2R	ENSDARG00000086262
danio_rerio	F2R	ENSDARG00000087469
danio_rerio	F2R	ENSDARG00000090041
mus_musculus	F2r	ENSMUSG00000048376
rattus_norvegicus	F2r	ENSRNOG00000048043

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

Proteinase-activated receptor 1 — P25116 (reviewed: P25116)

Alternative names: Coagulation factor II receptor, Thrombin receptor

All UniProt accessions (2): P25116, G3XAL6

UniProt curated annotations — full annotation on UniProt →

Function. High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores. The thrombin-activated receptor signaling pathway is mediated through PTX-insensitive G proteins, activation of phospholipase C resulting in the production of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) which binds to InsP3 receptors causing calcium release from the stores. In astrocytes, the calcium released into the cytosol allows the Ca(2+)-dependent release of L-glutamate into the synaptic cleft through BEST1, that targets the neuronal postsynaptic GRIN2A/NMDAR receptor resulting in the synaptic plasticity regulation. May play a role in platelets activation and in vascular development. Mediates up-regulation of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, triggered by coagulation factor Xa (F10) in cardiac fibroblasts and umbilical vein endothelial cells.

Subcellular location. Cell membrane.

Tissue specificity. Platelets and vascular endothelial cells.

Post-translational modifications. Proteolytic cleavage by thrombin generates a new N-terminus that functions as a tethered ligand. Also proteolytically cleaved by cathepsin CTSG. Cleavage at 41-Arg-|-Ser-42 by CTSG and GZMK results in receptor activation while cleavage at 55-Phe-|-Trp-56 results in inhibition of receptor activation. Phosphorylated in the C-terminal tail; probably mediating desensitization prior to the uncoupling and internalization of the receptor.

Domain organisation. The cleaved signal peptide may not be degraded and may function as an intracellular angiogenesis inhibitor peptide known as parstatin.

Induction. Up-regulated by coagulation factor X (F10) (activated).

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

RefSeq proteins (2): NP_001298242, NP_001983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000935	Thrmbn_rcpt	Family
IPR003912	Protea_act_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (60 total): helix 16, topological domain 8, transmembrane region 7, sequence variant 6, glycosylation site 5, strand 4, turn 3, site 2, mutagenesis site 2, sequence conflict 2, signal peptide 1, propeptide 1, chain 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3LU9	X-RAY DIFFRACTION	1.8
3BEF	X-RAY DIFFRACTION	2.2
3HKI	X-RAY DIFFRACTION	2.2
3VW7	X-RAY DIFFRACTION	2.2
1NRR	X-RAY DIFFRACTION	2.4
3HKJ	X-RAY DIFFRACTION	2.6
9D4Z	ELECTRON MICROSCOPY	2.74
1NRP	X-RAY DIFFRACTION	3
8XOR	ELECTRON MICROSCOPY	3
1NRN	X-RAY DIFFRACTION	3.1
1NRO	X-RAY DIFFRACTION	3.1
8XOS	ELECTRON MICROSCOPY	3.2
1NRQ	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25116-F1	74.50	0.45

Antibody-complex structures (SAbDab): 3 — 8XOR, 8XOS, 9D4Z

Functional residue map

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

Catalytic / active sites (2): 41–42 (cleavage; by thrombin, gzmk and ctsg); 55–56 (cleavage; by ctsg)

Post-translational modifications (1): 418

Disulfide bonds (1): 175–254

Glycosylation sites (5): 35, 62, 75, 250, 259

Mutagenesis-validated functional residues (2):

Position	Phenotype
41	abolished and activation cleavage by gzmk.
55–56	abolishes cleavage by ctsg but not by thrombin.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140875

MSigDB gene sets: 539 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_REGULATION_OF_COAGULATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_VESICLE_ORGANIZATION, GOLDRATH_IMMUNE_MEMORY

GO Biological Process (47): connective tissue replacement involved in inflammatory response wound healing (GO:0002248), negative regulation of glomerular filtration (GO:0003105), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), establishment of synaptic specificity at neuromuscular junction (GO:0007529), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), response to wounding (GO:0009611), anatomical structure morphogenesis (GO:0009653), platelet activation (GO:0030168), regulation of blood coagulation (GO:0030193), positive regulation of blood coagulation (GO:0030194), positive regulation of cell migration (GO:0030335), response to lipopolysaccharide (GO:0032496), regulation of interleukin-1 beta production (GO:0032651), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of collagen biosynthetic process (GO:0032967), positive regulation of Rho protein signal transduction (GO:0035025), dendritic cell homeostasis (GO:0036145), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), cell-cell junction maintenance (GO:0045217), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of vasoconstriction (GO:0045907), positive regulation of smooth muscle contraction (GO:0045987), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), regulation of synaptic plasticity (GO:0048167), homeostasis of number of cells within a tissue (GO:0048873), release of sequestered calcium ion into cytosol (GO:0051209), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of calcium ion transport (GO:0051928), platelet dense granule organization (GO:0060155), positive regulation of ERK1 and ERK2 cascade (GO:0070374), thrombin-activated receptor signaling pathway (GO:0070493)

GO Molecular Function (6): G-protein alpha-subunit binding (GO:0001965), G protein-coupled receptor activity (GO:0004930), signaling receptor binding (GO:0005102), thrombin-activated receptor activity (GO:0015057), G-protein beta-subunit binding (GO:0031681), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), caveola (GO:0005901), cell surface (GO:0009986), platelet dense tubular network (GO:0031094), neuromuscular junction (GO:0031594), postsynaptic membrane (GO:0045211), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Platelet activation, signaling and aggregation	1
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood coagulation	3
protein binding	3
cellular anatomical structure	3
G protein-coupled receptor signaling pathway	2
cell population proliferation	2
regulation of cell population proliferation	2
positive regulation of cytokine production	2
endosome	2
intracellular membrane-bounded organelle	2
wound healing involved in inflammatory response	1
connective tissue replacement	1
regulation of glomerular filtration	1
glomerular filtration	1
negative regulation of multicellular organismal process	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
regulation of biological quality	1
neuromuscular junction development	1
synapse organization	1
positive regulation of cellular process	1
negative regulation of cellular process	1
response to stress	1
developmental process	1
anatomical structure development	1
cell activation	1
regulation of response to external stimulus	1
regulation of coagulation	1
regulation of wound healing	1
regulation of hemostasis	1
regulation of blood coagulation	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to molecule of bacterial origin	1
response to lipid	1

Protein interactions and networks

STRING

2056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F2R	PROCR	Q9UNN8	978
F2R	THBD	P07204	965
F2R	GNAQ	P50148	892
F2R	EPRS1	P07814	889
F2R	PITRM1	Q5JRX3	871
F2R	MMP1	P03956	828
F2R	GNA12	Q03113	824
F2R	F3	P13726	817
F2R	F2	P00734	793
F2R	MARK3	P27448	782
F2R	S1PR3	Q99500	781
F2R	SELP	P16109	772
F2R	TFPI	P10646	728
F2R	ITGA2B	P08514	700
F2R	CCL2	P13500	694

IntAct

39 interactions, top by confidence:

A	B	Type	Score
PROCR	F2R	psi-mi:“MI:0915”(physical association)	0.640
PROCR	F2R	psi-mi:“MI:0914”(association)	0.640
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
F2R	F2	psi-mi:“MI:0407”(direct interaction)	0.440
F2R	TMED2	psi-mi:“MI:0915”(physical association)	0.400
F2R	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	F2R	psi-mi:“MI:0915”(physical association)	0.400
F2R	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	F2R	psi-mi:“MI:0915”(physical association)	0.400
F2R	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	F2R	psi-mi:“MI:0915”(physical association)	0.400
GNA13	F2R	psi-mi:“MI:0915”(physical association)	0.400
CHRD	F2R	psi-mi:“MI:0915”(physical association)	0.370
ATP13A2	F2R	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
CRYL1	MYO9A	psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
F2R	CAV1	psi-mi:“MI:0914”(association)	0.350
CAV1	F2R	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): F2R (Affinity Capture-Western), F2R (Co-localization), F2R (Co-localization), ARRDC3 (FRET), PDCD6IP (Affinity Capture-Western), MAPK14 (Affinity Capture-Western), TAB1 (Affinity Capture-Western), TAB2 (Affinity Capture-Western), F2R (Affinity Capture-MS), F2R (Affinity Capture-MS), CXCL14 (Reconstituted Complex), F2R (Reconstituted Complex), SNX1 (Affinity Capture-Western), F2R (Affinity Capture-MS), F2R (Affinity Capture-MS)

ESM2 similar proteins: A0A4W3GG95, A7YY44, B0F9W3, B0UXR0, B2GV46, B3G515, B5X337, E7FEL0, O00398, O46685, O70526, P21556, P25023, P25105, P25116, P26824, P30411, P30558, P32299, P43657, P46002, P46093, P49019, P50132, P56488, Q00991, Q15743, Q1JQB3, Q28642, Q3UFD7, Q4G072, Q4KLH9, Q61038, Q62035, Q80Z39, Q8BFQ3, Q8BFU7, Q8BLG2, Q8BMC0, Q8BUD0

Diamond homologs: A7YY44, B2GV46, D4A7K7, E9QJ73, F1MV99, O00254, O08565, O08675, O08858, O09047, O42179, O62747, O88634, O88680, O97571, P21109, P25024, P25025, P25116, P26824, P30558, P32250, P32745, P33766, P35344, P35383, P35411, P41231, P41232, P43657, P47749, P47900, P48042, P48748, P49238, P55085, P55086, P55919, P55920, P56488

SIGNOR signaling

54 interactions.

A	Effect	B	Mechanism
F2R	up-regulates	GNA13
F2R	down-regulates	LATS1
F2R	down-regulates	LATS2
F2R	up-regulates	GNA13	binding
F2R	up-regulates	GNAI1	binding
F2	up-regulates	F2R	cleavage
F2R	up-regulates	GNA12	binding
F2	up-regulates	F2R	binding
F2R	“up-regulates quantity by expression”	RAB3A	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	TNFRSF12A	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	CORO1C	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	KLF6	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	THBS1	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	CD44	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	SDC4	“transcriptional regulation”
TWIST2	“down-regulates quantity by repression”	F2R	“transcriptional regulation”
TWIST1	“down-regulates quantity by repression”	F2R	“transcriptional regulation”
F2R	“up-regulates activity”	GNAI1	binding
F2R	“up-regulates activity”	GNAI3	binding
F2R	“up-regulates activity”	GNAO1	binding
F2R	“up-regulates activity”	GNAZ	binding
F2R	“up-regulates activity”	GNAQ	binding
F2R	“up-regulates activity”	GNA14	binding
F2R	“up-regulates activity”	GNA15	binding
F2R	“up-regulates activity”	GNA12	binding
“PAR-1 (Protease-Activated Receptor) Selective Activating Peptide”	“up-regulates activity”	F2R	“chemical activation”
F2R	down-regulates	LATS1/2
STK11	“up-regulates activity”	F2R	phosphorylation
BMX	“down-regulates activity”	F2R	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	5	8.8×	5e-03
positive regulation of gene expression	5	7.8×	8e-03
G protein-coupled receptor signaling pathway	5	7.2×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

277 predictions. Top by Δscore:

Variant	Effect	Δscore
5:76732312:A:AG	acceptor_gain	1.0000
5:76732313:G:GA	acceptor_gain	1.0000
5:76716392:CCAG:C	donor_loss	0.9900
5:76716393:CAG:C	donor_loss	0.9900
5:76716396:G:GA	donor_loss	0.9900
5:76716397:T:A	donor_loss	0.9900
5:76732308:TTTCA:T	acceptor_loss	0.9900
5:76732309:TTCA:T	acceptor_loss	0.9900
5:76732310:TCAG:T	acceptor_loss	0.9900
5:76732311:CAG:C	acceptor_loss	0.9900
5:76732312:AG:A	acceptor_loss	0.9900
5:76732313:G:GC	acceptor_loss	0.9900
5:76732313:GA:G	acceptor_gain	0.9900
5:76732313:GAAT:G	acceptor_gain	0.9900
5:76732313:GAATC:G	acceptor_gain	0.9900
5:76716396:G:GG	donor_gain	0.9800
5:76716391:GCCAG:G	donor_gain	0.9700
5:76732313:GAA:G	acceptor_gain	0.9700
5:76732306:T:G	acceptor_gain	0.9600
5:76716947:G:GT	donor_gain	0.9200
5:76732305:A:AG	acceptor_gain	0.9200
5:76730601:C:G	donor_gain	0.8900
5:76716825:G:GT	donor_gain	0.8700
5:76732300:A:G	acceptor_gain	0.8600
5:76716246:TG:T	donor_gain	0.8200
5:76732301:T:G	acceptor_gain	0.7700
5:76732299:A:AG	acceptor_gain	0.7100
5:76716663:G:GT	donor_gain	0.7000
5:76730600:GCTGG:G	donor_gain	0.7000
5:76716238:A:T	donor_gain	0.6900

AlphaMissense

2768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:76732571:A:C	S116R	0.998
5:76732573:C:A	S116R	0.998
5:76732573:C:G	S116R	0.998
5:76732814:A:C	S197R	0.998
5:76732816:C:A	S197R	0.998
5:76732816:C:G	S197R	0.998
5:76733303:A:C	S360R	0.998
5:76733305:C:A	S360R	0.998
5:76733305:C:G	S360R	0.998
5:76733306:A:C	S361R	0.998
5:76733308:C:A	S361R	0.998
5:76733308:C:G	S361R	0.998
5:76732729:G:C	W168C	0.996
5:76732729:G:T	W168C	0.996
5:76732904:T:A	W227R	0.996
5:76732904:T:C	W227R	0.996
5:76733201:T:C	F326L	0.996
5:76733203:C:A	F326L	0.996
5:76733203:C:G	F326L	0.996
5:76733312:A:C	S363R	0.996
5:76733314:C:A	S363R	0.996
5:76733314:C:G	S363R	0.996
5:76732824:G:C	R200P	0.995
5:76732812:T:A	I196K	0.994
5:76732585:C:A	N120K	0.993
5:76732585:C:G	N120K	0.993
5:76732656:T:C	L144P	0.993
5:76732664:G:C	A147P	0.993
5:76733090:T:C	C289R	0.993
5:76732727:T:A	W168R	0.992

dbSNP variants (sampled 300 via entrez): RS1000009737 (5:76731777 C>A,T), RS1000197474 (5:76734293 G>A), RS1000200777 (5:76722193 C>T), RS1000302704 (5:76735447 C>T), RS1000476355 (5:76716193 C>G,T), RS1000633032 (5:76734619 C>T), RS1000681999 (5:76728815 C>G,T), RS1001326957 (5:76717391 C>T), RS1001516381 (5:76719582 C>G,T), RS1001525089 (5:76720742 T>A), RS1001624528 (5:76726314 G>A), RS1001747178 (5:76714919 G>A), RS1001960097 (5:76724743 T>C), RS1001983848 (5:76734156 C>A,G,T), RS1001988365 (5:76714750 T>C)

Disease associations

OMIM: gene MIM:187930 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001335_13	Mean platelet volume	1.000000e-15
GCST001337_14	Platelet count	1.000000e-09
GCST004616_7	Platelet distribution width	8.000000e-23
GCST006218_55	Erosive tooth wear (severe vs non-severe)	8.000000e-10
GCST006218_91	Erosive tooth wear (severe vs non-severe)	8.000000e-06
GCST006226_16	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST009268_10	Dental caries (decayed, missing and filled tooth surfaces)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3974 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,259 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL493982	VORAPAXAR	4	1,021
CHEMBL2103856	ATOPAXAR	2	208
CHEMBL2105699	ATOPAXAR HYDROBROMIDE	2	30

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs168753	F2R		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Proteinase-activated receptors

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
vorapaxar	Antagonist	8.09	pKi
[3H]haTRAP	Agonist	7.82	pKd
atopaxar	Antagonist	7.72	pIC50
SCH-79797	Antagonist	7.15	pIC50
RWJ-56110	Antagonist	6.36	pIC50
TFLLR-NH2	Full agonist	5.41	pEC50
F16357	Agonist	5.19	pIC50

Binding affinities (BindingDB)

176 measured of 176 human assays (176 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[6-[(E)-2-[(3R,4R,7aR)-6,6-difluoro-7a-[hydroxy(1,3-thiazol-4-yl)methyl]-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	0.9 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
(3R,4R,5S,7aR)-4-[(E)-2-[5-(2-chlorophenyl)-2-pyridinyl]ethenyl]-6,6-difluoro-3,5-dimethyl-7a-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]-3a,4,5,7-tetrahydro-3H-2-benzofuran-1-one	IC50	0.9 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
(3R,4R,5S,7aR)-4-[(E)-2-[5-(2-chlorophenyl)-2-pyridinyl]ethenyl]-6,6-difluoro-3,5-dimethyl-7a-[(1-methyltetrazol-5-yl)methyl]-3a,4,5,7-tetrahydro-3H-2-benzofuran-1-one	IC50	1 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,7aR)-6,6-difluoro-7a-[hydroxy(1,3-thiazol-2-yl)methyl]-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.2 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,7aR)-6,6-difluoro-7a-[hydroxy(1,3-oxazol-2-yl)methyl]-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.2 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
(3R,4R,5S,7aR)-4-[(E)-2-[5-(2-chlorophenyl)-2-pyridinyl]ethenyl]-6,6-difluoro-3,5-dimethyl-7a-(1,2,4-oxadiazol-3-ylmethyl)-3a,4,5,7-tetrahydro-3H-2-benzofuran-1-one	IC50	1.2 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aR)-7a-(aminomethyl)-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]-6-methylbenzonitrile	IC50	1.2 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(1,3-thiazol-5-ylmethylamino)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,7aS)-6,6-difluoro-3,5-dimethyl-7a-(4-methyltriazol-1-yl)-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.4 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S)-6,6-difluoro-3,5-dimethyl-1-oxo-3,3a,4,5,7,7a-hexahydro-2H-isoindol-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.5 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S)-6,6-difluoro-3,5-dimethyl-1-oxo-3,3a,4,5,7,7a-hexahydro-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.6 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(1,3-thiazol-4-ylmethylamino)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.6 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]pyrimidin-2-yl]-N,N-dimethylbenzamide	IC50	1.67 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-[(1R,3aS,6R,7R,7aR)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-4-fluorobenzamide	IC50	1.7 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-methoxy-6-[6-methoxy-4-[[2-(4-methoxyphenyl)pyrimidin-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	IC50	1.8 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-[6-[(E)-2-[(3R,4R,7aR)-6,6-difluoro-7a-[hydroxy(1,3-oxazol-4-yl)methyl]-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	1.9 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aS)-6,6-difluoro-7a-hydroxy-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
(3R,4R,5S,7aR)-4-[(E)-2-[5-(2-chlorophenyl)-2-pyridinyl]ethenyl]-6,6-difluoro-3,5-dimethyl-7a-[(2-methyltetrazol-5-yl)methyl]-3a,4,5,7-tetrahydro-3H-2-benzofuran-1-one	IC50	2.1 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,7aS)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(1,3-thiazol-2-ylmethylamino)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2.2 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]benzamide	IC50	2.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aR)-7a-(aminomethyl)-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,7aS)-6,6-difluoro-3,5-dimethyl-7a-(1,3-oxazol-4-ylmethylamino)-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2.4 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aR,4R,5S,7aS)-6,6-difluoro-7a-methoxy-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2.5 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
(3R,4R,5S)-4-[(E)-2-[5-(2-chlorophenyl)-2-pyridinyl]ethenyl]-6,6-difluoro-3,5-dimethyl-3,3a,4,5,7,7a-hexahydro-2-benzofuran-1-one	IC50	2.7 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aR)-6,6-difluoro-7a-(hydroxymethyl)-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2.7 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-7a-(cyclopropylmethylamino)-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	2.7 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-3-cyanobenzamide	IC50	2.7 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-1,3-thiazole-2-carboxamide	IC50	2.8 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-methoxy-6-[6-methoxy-4-[[3-(5-methoxy-2-pyridinyl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	IC50	2.86 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-4-cyanobenzamide	IC50	2.9 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
6-(4-((2-(2-fluoropyridin-4-yl)pyrimidin-4-yl)methoxy)-6-methoxybenzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	IC50	2.97 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-[6-[(E)-2-[(3R,4R,7aR)-6,6-difluoro-7a-[hydroxy(pyridin-2-yl)methyl]-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-6,6-difluoro-3,5-dimethyl-7a-[(1-methylimidazol-2-yl)methylamino]-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-3-fluorobenzamide	IC50	3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-6-chloropyridine-3-carboxamide	IC50	3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aS)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(tetrazol-1-yl)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	3.1 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(pyridin-2-ylmethylamino)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	3.1 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
(1R,3aR,7R)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-N-cyclobutyl-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-carboxamide	IC50	3.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[(1R,3aR,6S,7R)-7-[(E)-2-[5-(2-chlorophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]acetonitrile	IC50	3.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aS)-7a-amino-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]-6-methylbenzonitrile	IC50	3.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
methyl (1R,3aR,6S,7R)-5,5-difluoro-7-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-carboxylate	IC50	3.4 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-5-methyl-1,2-oxazole-3-carboxamide	IC50	3.4 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
N-[(1R,3aS,6S,7R,7aS)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]cyclopropanecarboxamide	IC50	3.5 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-methoxy-6-[6-methoxy-4-[[3-methoxy-5-(2-methoxypyrimidin-5-yl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	IC50	3.61 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[3-(5-methoxypyrazin-2-yl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	IC50	3.63 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-[(1R,3aR,7R)-7-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-5,5-difluoro-1,6-dimethyl-3-oxo-4,6,7,7a-tetrahydro-1H-2-benzofuran-3a-yl]-1-methylpyrazole-3-carboxamide	IC50	3.7 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,7aS)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(pyridin-4-ylmethylamino)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	3.9 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aS)-7a-(cyclobutylamino)-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	4.1 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,4R,5S,7aS)-6,6-difluoro-7a-(hydroxyamino)-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	4.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-7a-[(3-chloro-2-hydroxypropyl)amino]-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	IC50	4.3 nM	US-9340530: Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists

ChEMBL bioactivities

1114 potent at pChembl≥5 of 1209 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Kd	0.04	nM	CHEMBL267059
9.82	Kd	0.15	nM	RWJ-58259
9.36	Kd	0.44	nM	CHEMBL275003
9.15	Kd	0.7	nM	CHEMBL275946
9.09	Kd	0.82	nM	CHEMBL428311
9.05	IC50	0.9	nM	CHEMBL4111522
9.05	IC50	0.9	nM	CHEMBL3954641
9.00	IC50	0.99	nM	CHEMBL3939323
9.00	IC50	1	nM	CHEMBL3942006
8.96	IC50	1.1	nM	VORAPAXAR
8.96	Ki	1.1	nM	VORAPAXAR
8.92	IC50	1.2	nM	CHEMBL4111522
8.92	IC50	1.2	nM	CHEMBL4113709
8.92	IC50	1.2	nM	CHEMBL4114937
8.92	IC50	1.2	nM	CHEMBL3931589
8.92	IC50	1.2	nM	CHEMBL3966338
8.89	IC50	1.3	nM	CHEMBL3091980
8.89	IC50	1.3	nM	CHEMBL3897109
8.89	Kd	1.3	nM	RWJ-54003
8.85	IC50	1.4	nM	CHEMBL4106770
8.82	IC50	1.5	nM	VORAPAXAR
8.82	IC50	1.5	nM	CHEMBL3933019
8.80	IC50	1.6	nM	CHEMBL3937747
8.80	IC50	1.6	nM	CHEMBL3968240
8.77	IC50	1.7	nM	CHEMBL4113548
8.74	Ki	1.8	nM	CHEMBL442649
8.72	IC50	1.9	nM	CHEMBL4110608
8.70	IC50	2	nM	CHEMBL3897962
8.70	IC50	2	nM	CHEMBL5084411
8.68	IC50	2.1	nM	CHEMBL3930471
8.66	IC50	2.2	nM	CHEMBL3091980
8.66	IC50	2.2	nM	CHEMBL4110608
8.66	IC50	2.2	nM	CHEMBL4111197
8.66	Kd	2.2	nM	CHEMBL269345
8.64	IC50	2.3	nM	CHEMBL3932907
8.64	IC50	2.3	nM	CHEMBL3927578
8.62	IC50	2.4	nM	CHEMBL4109959
8.62	Kd	2.4	nM	CHEMBL268328
8.60	IC50	2.5	nM	CHEMBL4113709
8.60	IC50	2.5	nM	CHEMBL3985342
8.57	IC50	2.7	nM	CHEMBL3091993
8.57	Ki	2.7	nM	CHEMBL371069
8.57	IC50	2.7	nM	CHEMBL3980810
8.57	IC50	2.7	nM	CHEMBL3930467
8.57	IC50	2.7	nM	CHEMBL3907652
8.57	IC50	2.7	nM	CHEMBL3961310
8.55	IC50	2.8	nM	CHEMBL3916203
8.54	IC50	2.9	nM	CHEMBL3091993
8.54	IC50	2.9	nM	CHEMBL3908486
8.52	Ki	3	nM	CHEMBL3985900

PubChem BioAssay actives

933 with measured affinity, of 1621 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
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-(3,4-difluorophenyl)propanoyl]amino]-N-(pyridin-4-ylmethyl)pentanamide	154615: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	<0.0001	uM
(2S)-4-amino-N-benzyl-2-[[(2S)-2-[[1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indazol-6-yl]carbamoylamino]-3-(3,4-difluorophenyl)propanoyl]amino]butanamide	154614: Binding Affinity of ligand against Protease-activated Receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0001	uM
2-amino-4-[[(1R)-2-(benzylamino)-1-[[(2S)-2-[[1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-(3,4-difluorophenyl)propanoyl]amino]-2-oxoethyl]amino]butanoic acid	154616: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0004	uM
(2S)-N-benzyl-5-(diaminomethylideneamino)-2-[[(2S)-2-[[1-[(4-fluorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-phenylpropanoyl]amino]pentanamide	154615: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0007	uM
(2S)-N-benzyl-5-(diaminomethylideneamino)-2-[[(2S)-2-[[1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-(3,4-difluorophenyl)propanoyl]amino]pentanamide	154615: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0008	uM
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aR)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(1H-pyrazol-5-yl)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	1322450: Antagonist activity at PAR-1 in HEK293 cells incubated for 30 mins followed by Ala-parafluoroPhe-Arg-Cha-Cit-Try-NH2 substrate addition by calcium-5 dye based FLIPR assay	ic50	0.0010	uM
Vorapaxar	1056260: Displacement of [3H]haTRAP from PAR1 in human platelet membranes after 60 mins by scintillation counting analysis	ic50	0.0011	uM
(2S)-N-benzyl-5-(diaminomethylideneamino)-2-[[(2S)-2-[[1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-(4-methoxyphenyl)propanoyl]amino]pentanamide	154615: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0013	uM
N-[(1R,3aS,7aS)-1-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-2-yl]-N-methylmethanesulfonamide	1056260: Displacement of [3H]haTRAP from PAR1 in human platelet membranes after 60 mins by scintillation counting analysis	ic50	0.0013	uM
ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-cyanophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0018	uM
2-[6-[(E)-2-[(3R,3aR,4R,5S,7aS)-6,6-difluoro-7a-hydroxy-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0020	uM
(2S)-N-benzyl-5-(diaminomethylideneamino)-2-[[(2S)-2-[[1-[(4-fluorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-(4-methoxyphenyl)propanoyl]amino]pentanamide	154615: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0022	uM
(2S)-N-benzyl-5-(diaminomethylideneamino)-2-[[(2S)-3-(4-methoxyphenyl)-2-[[3-(pyrrolidin-1-ylmethyl)-1-[[4-(trifluoromethoxy)phenyl]methyl]indol-6-yl]carbamoylamino]propanoyl]amino]pentanamide	154615: Binding affinity against Protease-activated receptor (PAR-1) using [3H]-s-(p-F-Phe)-homoarginine-L-homoarginine-KY-NH2, 10 nM (Kd= 15 nM)	kd	0.0024	uM
[(1R,3aS,7aS)-1-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-2-methyl-1,3,3a,4,5,6,7,7a-octahydroinden-2-yl] carbamate	1056260: Displacement of [3H]haTRAP from PAR1 in human platelet membranes after 60 mins by scintillation counting analysis	ic50	0.0027	uM
(3R,3aS,4S,4aR,8aS,9aR)-3-methyl-4-[(E)-2-[5-[3-(trifluoromethyl)phenyl]-2-pyridinyl]ethenyl]-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-3H-benzo[f][2]benzofuran-1-one	254321: Inhibitory constant against Protease-activated receptor 1	ki	0.0027	uM
2-[6-[(E)-2-[(3R,3aR,4R,5S,7aS)-6,6-difluoro-7a-hydroxy-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]-6-methylbenzonitrile	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0030	uM
(3R,3aS,4S,5R,6S,7aR)-4-[5-(3-fluorophenyl)-2-pyridinyl]-3,5,6-trimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0030	uM
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aR)-7a-(5-amino-1,3,4-oxadiazol-2-yl)-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	1322450: Antagonist activity at PAR-1 in HEK293 cells incubated for 30 mins followed by Ala-parafluoroPhe-Arg-Cha-Cit-Try-NH2 substrate addition by calcium-5 dye based FLIPR assay	ic50	0.0031	uM
ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-1-methyl-3-oxo-9-[(E)-2-[5-[3-(trifluoromethyl)phenyl]-2-pyridinyl]ethenyl]-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]-N-methylcarbamate	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0037	uM
ethyl (3R,3aS,4S,5R,6R,6aS,9aR)-4-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-3,5,6-trimethyl-1-oxo-3,3a,4,5,6,6a,7,9-octahydrofuro[3,4-d]isoindole-8-carboxylate	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-(N-acetyl-3-prop-2-ynoylanilino)-3-(4-fluorophenyl)propanoyl]amino]-3-[4-(diaminomethylideneamino)phenyl]propanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-methylpentanamide	211933: Antagonistic activity against tritiated agonist (SFFLRR-NH2, at 25 nM) binding to human platelet membranes measured by the GTPase assay	ic50	0.0040	uM
ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]-N-methylcarbamate	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0041	uM
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aR)-6,6-difluoro-3,5-dimethyl-1-oxo-7a-(2-oxo-3H-1,3,4-oxadiazol-5-yl)-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	1322450: Antagonist activity at PAR-1 in HEK293 cells incubated for 30 mins followed by Ala-parafluoroPhe-Arg-Cha-Cit-Try-NH2 substrate addition by calcium-5 dye based FLIPR assay	ic50	0.0042	uM
ethyl (1R,3aR,4aS,8aS,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-1,3a,4,4a,5,7,8,8a,9,9a-decahydrofuro[3,4-g]isoquinoline-6-carboxylate	298295: Displacement of [3H]haTRAP from PAR1 in human platelet membrane	ki	0.0043	uM
1-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]-3-methylurea	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0044	uM
(3R,3aR,4S,5R,6S,7aS)-5-ethyl-7a-hydroxy-3,6-dimethyl-4-[(E)-2-(5-thiophen-3-yl-2-pyridinyl)ethenyl]-3,3a,4,5,6,7-hexahydro-2-benzofuran-1-one	653501: Displacement of [3H]haTRAP from human PAR1 after 1 hr by TopCount scintillation counting	ic50	0.0046	uM
1-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]-3-ethylurea	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0048	uM
(3R,3aS,4R,5S,7aR)-6,6-difluoro-4-[5-(3-fluorophenyl)-2-pyridinyl]-3,5-dimethyl-3,3a,4,5,7,7a-hexahydro-2-benzofuran-1-one	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0050	uM
methyl N-[[(1R,3aR,4aS,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]methyl]carbamate	1065174: Displacement of [3H]haTRAP from PAR-1 isolated from human platelets by liquid scintillation counting analysis	ki	0.0050	uM
2-[6-[(E)-2-[(1’R,3’aR,4R,4’aR,8’aR,9’S,9’aS)-1’-methyl-2,3’-dioxospiro[1,3-oxazolidine-4,6’-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-9’-yl]ethenyl]-3-pyridinyl]benzonitrile	1155054: Displacement of [3H]haTRAP from PAR-1 receptor in human platelet membranes after 1 hr by scintillation counting analysis	ki	0.0051	uM
N-[(1R,3aS,7aS)-1-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-2-yl]-N-methylacetamide	1056260: Displacement of [3H]haTRAP from PAR1 in human platelet membranes after 60 mins by scintillation counting analysis	ic50	0.0054	uM
ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-methoxyphenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0059	uM
ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3,5-difluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0059	uM
2-[6-[(E)-2-[(3R,3aR,4R,5S,7aS)-7a-amino-6,6-difluoro-3,5-dimethyl-1-oxo-2,3,3a,4,5,7-hexahydroisoindol-4-yl]ethenyl]-3-pyridinyl]benzonitrile	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0060	uM
[(1R,3aS,7aS)-1-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-2-yl] methanesulfonate	1056259: Antagonist activity at PAR1 in washed human platelets assessed as inhibition of haTRAP-induced platelet aggregation preincubated for 1 hr followed by haTRAP addition measured for 10 mins by spectrophotometric analysis	ic50	0.0060	uM
methyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0061	uM
N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]acetamide	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0062	uM
(3R,3aS,4S,4aR,8aS,9aR)-4-[(E)-2-(6-hydroxyquinolin-2-yl)ethenyl]-3-methyl-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-3H-benzo[f][2]benzofuran-1-one	262192: Displacement of [3H]haTRAP from PAR1 in human platelet membrane	ic50	0.0063	uM
N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]propanamide	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0064	uM
(3R,3aR,4S,5R,6S,7aS)-5-ethyl-7a-hydroxy-3,6-dimethyl-4-[(E)-2-(5-phenyl-2-pyridinyl)ethenyl]-3,3a,4,5,6,7-hexahydro-2-benzofuran-1-one	653501: Displacement of [3H]haTRAP from human PAR1 after 1 hr by TopCount scintillation counting	ic50	0.0064	uM
N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]cyclopropanecarboxamide	407981: Displacement of [3H]haTRAP from PAR1 in human platelets	ki	0.0065	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[acetyl-[(E)-3-phenylprop-2-enoyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-[4-(diaminomethylideneamino)phenyl]propanoyl]amino]-N-[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1,5-diamino-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-4-methylpentanamide	211933: Antagonistic activity against tritiated agonist (SFFLRR-NH2, at 25 nM) binding to human platelet membranes measured by the GTPase assay	ic50	0.0066	uM
(3R,3aS,4S,5R,6R,6aS,9aR)-4-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-N-ethyl-3,5,6-trimethyl-1-oxo-3,3a,4,5,6,6a,7,9-octahydrofuro[3,4-d]isoindole-8-carboxamide	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0070	uM
(3R,3aS,4S,5R,6R,6aS,9aR)-4-[(E)-2-[5-(2-cyanophenyl)-2-pyridinyl]ethenyl]-N,3,5,6-tetramethyl-1-oxo-3,3a,4,5,6,6a,7,9-octahydrofuro[3,4-d]isoindole-8-carboxamide	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0070	uM
(3aS,9R,9aR)-5,6-difluoro-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-3a,4,9,9a-tetrahydro-1H-benzo[f][2]benzofuran-3-one	299271: Displacement of [3H]haTRAP from PAR1	ic50	0.0070	uM
2-[6-[(E)-2-[(3R,3aS,4R,5S,7aS)-7a-amino-6,6-difluoro-3,5-dimethyl-1-oxo-3a,4,5,7-tetrahydro-3H-2-benzofuran-4-yl]ethenyl]-3-pyridinyl]benzonitrile	1823390: Antagonist activity at human PAR-1 expressed in HEK293 cells assessed as reduction in TRAP induced calcium signal at 3 uM by FLIPR analysis	ic50	0.0070	uM
(1R,3aS,7aS)-1-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]spiro[1,3,3a,4,5,6,7,7a-octahydroindene-2,5’-1,3-oxazolidine]-2’-one	1056259: Antagonist activity at PAR1 in washed human platelets assessed as inhibition of haTRAP-induced platelet aggregation preincubated for 1 hr followed by haTRAP addition measured for 10 mins by spectrophotometric analysis	ic50	0.0072	uM
(2S)-N-[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-[[(2S)-3-[4-(diaminomethylideneamino)phenyl]-2-[[(2S)-3-(4-fluorophenyl)-2-[[(E)-3-phenylprop-2-enoyl]amino]propanoyl]amino]propanoyl]amino]-4-methylpentanamide	211932: Inhibition of [3H]S-(p-F-Phe)-Har-L-Har-KY-NH2 binding to a thrombin receptor (PAR-1) membrane preparation.	ic50	0.0075	uM
(3aR,4R,9aS)-4-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-3a,4,9,9a-tetrahydro-3H-benzo[f][2]benzofuran-1-one	299271: Displacement of [3H]haTRAP from PAR1	ic50	0.0075	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[acetyl-[(E)-3-phenylprop-2-enoyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-[4-(diaminomethylideneamino)phenyl]propanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-methylpentanamide	211933: Antagonistic activity against tritiated agonist (SFFLRR-NH2, at 25 nM) binding to human platelet membranes measured by the GTPase assay	ic50	0.0075	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Particulate Matter	decreases expression, increases abundance, increases expression	4
Arsenic	affects expression, increases abundance, increases expression, decreases expression	3
Valproic Acid	affects expression, increases expression	3
cobaltous chloride	affects cotreatment, increases expression, decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases reaction	2
Air Pollutants	decreases expression, increases abundance	2
Aspirin	decreases expression	2
Copper	affects binding, decreases expression	2
Doxorubicin	affects expression, increases expression	2
Hydrogen Peroxide	increases expression, affects expression	2
Oxygen	increases expression, decreases reaction	2
Plant Extracts	affects cotreatment, increases expression, decreases reaction	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Silver Compounds	affects expression, affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
lead acetate	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
steviol	decreases expression	1
stevioside	decreases expression	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
butyraldehyde	increases expression	1
rebaudioside A	decreases expression	1

ChEMBL screening assays

176 unique, capped per target: 89 binding, 83 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002710	Functional	Antagonist activity at PAR1 receptor assessed as inhibition of PAR1AP-induced platelet aggregation in human blood after 10 mins by chronolog dual channel aggregometry	Synthesis and pharmacological evaluation of peptide-mimetic protease-activated receptor-1 antagonists containing novel heterocyclic scaffolds. — Bioorg Med Chem
CHEMBL1026653	Binding	Displacement of [125I]thrombin from thrombin receptor in human platelet membrane	Aplysillin A, a thrombin receptor antagonist from the marine sponge Aplysina fistularis fulva. — J Nat Prod
CHEMBL4407152	ADMET	Antagonist activity at PAR1 in human platelet rich plasma assessed as inhibition of SFFLRR-induced platelet aggregation preincubated for 5 mins followed by SFFLRR addition	Discovery of Potent Protease-Activated Receptor 4 Antagonists with in Vivo Antithrombotic Efficacy. — J Med Chem

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2WS	Abcam HEK293T F2R KO	Transformed cell line	Female
CVCL_D1WA	Abcam A-549 F2R KO	Cancer cell line	Male
CVCL_D2AN	Abcam HCT 116 F2R KO	Cancer cell line	Male
CVCL_D7PP	Ubigene A-549 F2R KO	Cancer cell line	Male
CVCL_D8L2	Ubigene HCT 116 F2R KO	Cancer cell line	Male
CVCL_D9EM	Ubigene HEK293 F2R KO	Transformed cell line	Female
CVCL_E0CY	Ubigene HeLa F2R KO	Cancer cell line	Female
CVCL_E0U3	Ubigene Hep G2 F2R KO	Cancer cell line	Male
CVCL_KX02	PathHunter CHO-K1 F2R beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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