F2RL3

Summary

F2RL3 (F2R like thrombin or trypsin receptor 3, HGNC:3540) is a protein-coding gene on chromosome 19p13.11, encoding Proteinase-activated receptor 4 (Q96RI0). Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis.

This gene encodes a member of the protease-activated receptor subfamily, part of the G-protein coupled receptor 1 family of proteins. The encoded receptor is proteolytically processed to reveal an extracellular N-terminal tethered ligand that binds to and activates the receptor. This receptor plays a role in blood coagulation, inflammation and response to pain. Hypomethylation at this gene may be associated with lung cancer in human patients.

Source: NCBI Gene 9002 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 91 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003950

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3540
Approved symbol	F2RL3
Name	F2R like thrombin or trypsin receptor 3
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	PAR4
Ensembl gene	ENSG00000127533
Ensembl biotype	protein_coding
OMIM	602779
Entrez	9002

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000248076, ENST00000599210

RefSeq mRNA: 1 — MANE Select: NM_003950 NM_003950

CCDS: CCDS12350

Canonical transcript exons

ENST00000248076 — 2 exons

Exon	Start	End
ENSE00000873498	16889573	16892606
ENSE00001228788	16888999	16889298

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 89.43.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6044 / max 111.5307, expressed in 309 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174446	0.8175	224
174444	0.3220	84
174449	0.2253	80
174448	0.0709	19
174445	0.0701	28
174450	0.0622	34
174447	0.0222	11
174451	0.0142	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	89.43	gold quality
upper lobe of left lung	UBERON:0008952	87.25	gold quality
lung	UBERON:0002048	79.85	gold quality
left lobe of thyroid gland	UBERON:0001120	79.33	gold quality
omental fat pad	UBERON:0010414	79.32	gold quality
thyroid gland	UBERON:0002046	79.13	gold quality
adipose tissue	UBERON:0001013	78.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.46	gold quality
islet of Langerhans	UBERON:0000006	74.68	gold quality
right lobe of thyroid gland	UBERON:0001119	73.23	gold quality
thoracic mammary gland	UBERON:0005200	72.15	gold quality
lower esophagus mucosa	UBERON:0035834	71.49	gold quality
monocyte	CL:0000576	70.96	gold quality
leukocyte	CL:0000738	70.36	gold quality
pancreas	UBERON:0001264	70.22	gold quality
body of stomach	UBERON:0001161	69.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.62	gold quality
transverse colon	UBERON:0001157	68.23	gold quality
colonic epithelium	UBERON:0000397	68.04	gold quality
small intestine	UBERON:0002108	67.84	gold quality
body of pancreas	UBERON:0001150	67.54	gold quality
gastrocnemius	UBERON:0001388	67.05	gold quality
stomach	UBERON:0000945	67.02	gold quality
adult mammalian kidney	UBERON:0000082	65.98	gold quality
mucosa of transverse colon	UBERON:0004991	65.65	gold quality
heart left ventricle	UBERON:0002084	65.41	gold quality
intestine	UBERON:0000160	65.14	gold quality
gall bladder	UBERON:0002110	65.13	gold quality
colon	UBERON:0001155	64.94	gold quality
lymph node	UBERON:0000029	64.87	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	28.16
E-ANND-3	yes	7.00
E-MTAB-5061	yes	6.82
E-MTAB-6075	no	44.18
E-ENAD-27	no	4.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, NR1H3

miRNA regulators (miRDB)

56 targeting F2RL3, 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-4775	99.98	75.00	6394
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-942-5P	99.41	68.40	1977

Literature-anchored findings (GeneRIF, showing 40)

• When expressed in respiratory epithelial cells and cell lines, protease-activated receptor 4 (PAR4)induces the release of IL-6, IL-8, and PGE2. (PMID:11907122)
• Activation of platelets via the PAR4 pathway, by treatment with PAR4 agonist peptide AYPGKF, results in thrombin-induced thromboxane production by platelets. (PMID:12006403)
• The signal from PAR4 stabilizes platelet-platelet aggregate formation in the absence of P2Y12 activation by ADP. (PMID:12008957)
• PAR4 is activated independently of GPIbalpha and ADP (PMID:12871418)
• Important role in regulation of thromboxane formation in platelets responding to thrombin through prolonged elevation of Ca(2+) and activation of phospholipase A(2). Can be activated by relatively low concentrations of thrombin in human platelets. (PMID:12888878)
• Protease-activated receptor-4 exodomains utilize dual prolines and an anionic retention motif for thrombin recognition and cleavage. (PMID:13678420)
• PAR-1 and PAR-4 have roles in activating GPIb translocation into the cytoskeleton in platelets (PMID:14521606)
• plasmin induces platelet aggregation primarily through slow cleavage of PAR-4; prolonged incubation with plasmin desensitized platelets to further stimulation by thrombin. (PMID:14973136)
• 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)
• beta- and gamma-thrombin selectively activate PAR-4; physiological roles are demonstrated (PMID:15203717)
• 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)
• new class of cell-penetrating inhibitors, termed pepducins, that provide insight into previously unidentified roles of PAR1 and PAR4 in protease signaling. (PMID:16952995)
• cooperative PAR(1)/PAR(4) signaling network that contributes to thrombin-mediated tumor cell migration in hepatocellular carcinoma (PMID:17323377)
• PARs (PAR-1, PAR-2, and PAR-4) are overexpressed in prostate cancer and may serve as potential predictors of recurrence. The data suggest potential role of PARs in autocrine and paracrine mechanisms of prostate cancer. (PMID:17373694)
• similar to the guinea-pig gallbladder, both PAR(1) and PAR(2) but not PAR(4) mediate muscle contraction in the human gallbladder (PMID:18179608)
• Results show the induction of Par-4 by the chemopreventive agent 3,3’ diindolylmethane in pancreatic cancer cells in vitro. (PMID:18427961)
• PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. (PMID:18480058)
• Coordinate activation of human platelet protease-activated receptor-1 and -4 in response to subnanomolar alpha-thrombin (PMID:18682394)
• PAR4 uses its anionic cluster to interact with alpha-thrombin. This interaction is important even in the presence of protease-activated receptor 1 (PAR1). (PMID:19053259)
• These data highlight the role of PAR4 as a new important player in the control of colon tumors and underline the critical role of ErbB-2 transactivation. (PMID:19058300)
• murine platelets are more sensitive to plasmin than human platelets due to differences in the primary sequence of PAR4. In contrast to thrombin-dependent activation of platelets,, mPAR3 inhibits plasmin-induced PAR4 activation. (PMID:19437337)
• both Cat-G and PAR(4) play key roles in generating and/or amplifying relapses in ulcerative colitis (PMID:19528350)
• Complement protease MASP-1 activates human endothelial cells through PAR4 cleavage (PMID:19667088)
• Human cytomegalovirus induces PARs expression through transcriptional activation in endothelial cells, increasing sensitivity to thrombin. (PMID:20155436)
• Thrombin enhances the migration of chondrosarcoma cells by increasing MMP-2 and MMP-13 expression through the PAR/PLC/PKCalpha/c-Src/NF-kappaB signal transduction pathway. (PMID:20175118)
• Data show that PAR1 and PAR4-activating peptides were as effective as thrombin in inducing annexin V binding in combination with collagen-related peptide in diluted whole blood and platelet rich plasma, but not in washed platelets. (PMID:20230207)
• SPSB1 and SPSB4 bind strongly to both Par-4 and VASA peptides. (PMID:20561531)
• Results suggest that lower levels of protease-activated receptors 1 and 4 contribute to the poor thrombin induced aggregation observed with newborn platelets, which can not be compensated by higher levels of GPIbalpha. (PMID:20807173)
• Low concentrations of alpha-thrombin accelerate tissue factor-induced thrombin generation on the surface of vascular smooth muscle cells, and this effect is mediated by PAR-3 and PAR-4. (PMID:20930172)
• Protease-activated receptor signaling in platelets activates cytosolic phospholipase A2alpha differently for cyclooxygenase-1 and 12-lipoxygenase catalysis. (PMID:21127289)
• High glucose enhances smooth muscle cell responsiveness to thrombin through transcriptional upregulation of PAR-4, mediated via PKC and NFkappaB. (PMID:21164077)
• The present study elucidates further differences in human platelet PAR signalling regulation and provides evidence for a cross-talk in which PAR4 signalling counteracts mechanisms involved in PAR1 signalling down-regulation. (PMID:21391917)
• Data show that frog TFF2 activates protease-activated receptor (PAR) 1 to induce human platelet aggregation, and suggest that human TFF2 promotes cell migration via PAR4. (PMID:21461878)
• down-regulation of PAR4 expression occurs frequently in gastric cancers and exhibits association with more aggressive gastric cancer (PMID:21635966)
• PKC inhibition markedly enhances Ca2+ signaling and phosphatidylserine exposure downstream of protease-activated receptor-1 but not protease-activated receptor-4 in human platelets. (PMID:21649850)
• PAR4 is down-regulated in the colonic mast cells of post-infectious irritable bowel syndrome. (PMID:22151913)
• The F2RL3 rs773857 risk allele homozygotes are associated with risk for increased platelet count and hyperactivity. (PMID:22228373)
• mutations that disrupted dimer formation had reduced calcium mobilization in response to the PAR4 agonist peptide. (PMID:22318735)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	F2RL3	ENSDARG00000079399
mus_musculus	F2rl3	ENSMUSG00000050147
rattus_norvegicus	F2rl3	ENSRNOG00000068093

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

Proteinase-activated receptor 4 — Q96RI0 (reviewed: Q96RI0)

Alternative names: Coagulation factor II receptor-like 3, Thrombin receptor-like 3

All UniProt accessions (2): Q96RI0, M0R0Y0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed, with highest levels in lung, pancreas, thyroid, testis and small intestine. Not expressed in brain, kidney, spinal cord and peripheral blood leukocytes. Also detected in platelets.

Post-translational modifications. A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.

Activity regulation. Activated upon interaction by mucunain, a cowhage (Mucuna pruriens) plant cysteine proteinase.

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

RefSeq proteins (1): NP_003941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR003912	Protea_act_rcpt	Family
IPR003944	Prot_act_rcpt_4	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (30 total): topological domain 8, transmembrane region 7, sequence variant 4, region of interest 2, mutagenesis site 2, signal peptide 1, propeptide 1, chain 1, site 1, glycosylation site 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2ZPK	X-RAY DIFFRACTION	1.8
3QDZ	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RI0-F1	80.67	0.53

Antibody-complex structures (SAbDab): 1 — 2ZPK

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 (1): 47–48 (cleavage; by thrombin or trypsin)

Disulfide bonds (1): 149–228

Glycosylation sites (1): 56

Mutagenesis-validated functional residues (2):

Position	Phenotype
47	no proteolytic cleavage (by thrombin or trypsin).
68	no effect on receptor activation.

Function

Pathways and Gene Ontology

Reactome pathways

3 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)

MSigDB gene sets: 186 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_VESICLE_ORGANIZATION, GOBP_PLATELET_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, MORF_RAD51L3, GOBP_MONOATOMIC_CATION_TRANSPORT, GOLDRATH_ANTIGEN_RESPONSE, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT

GO Biological Process (11): signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), blood coagulation (GO:0007596), response to wounding (GO:0009611), platelet activation (GO:0030168), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), platelet dense granule organization (GO:0060155), platelet aggregation (GO:0070527), hemostasis (GO:0007599), thrombin-activated receptor signaling pathway (GO:0070493)

GO Molecular Function (3): protease binding (GO:0002020), G protein-coupled receptor activity (GO:0004930), thrombin-activated receptor activity (GO:0015057)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
hemostasis	1
wound healing	1
coagulation	1
response to stress	1
cell activation	1
blood coagulation	1
release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
secretory granule organization	1
platelet activation	1
homotypic cell-cell adhesion	1
regulation of body fluid levels	1
enzyme binding	1
transmembrane signaling receptor activity	1
proteinase-activated receptor activity	1
thrombin-activated receptor signaling pathway	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F2RL3	D6RE68	D6RE68	744
F2RL3	AHRR	A9YTQ3	717
F2RL3	PAWR	Q96IZ0	694
F2RL3	NR1I2	O75469	611
F2RL3	MYO1G	B0I1T2	606
F2RL3	ALPG	P10696	591
F2RL3	LRRN3	Q9H3W5	554
F2RL3	GFI1	Q99684	505
F2RL3	GNG12	Q9UBI6	475
F2RL3	DAPK3	O43293	470
F2RL3	EPRS1	P07814	448
F2RL3	TAC3	Q9UHF0	441
F2RL3	F2	P00734	425
F2RL3	PRSS23	O95084	419
F2RL3	FAM167A	Q96KS9	398

IntAct

12 interactions, top by confidence:

A	B	Type	Score
	F2RL3	psi-mi:“MI:0915”(physical association)	0.580
F2RL3		psi-mi:“MI:0915”(physical association)	0.580
	CTNND1	psi-mi:“MI:0914”(association)	0.500
F2RL3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
F2RL3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
F2RL3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): F2RL3 (Synthetic Lethality), F2RL3 (Affinity Capture-RNA), F2RL3 (Affinity Capture-MS), F2RL3 (Affinity Capture-MS), F2RL3 (Affinity Capture-MS), F2RL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8PUB9, O00155, O00270, O14842, O14843, O15529, O43603, O46685, O60755, O88626, O88634, O88853, O88854, O88855, P0C5I1, P46092, P46093, P50132, Q149R9, Q15722, Q15743, Q1JQB3, Q3T181, Q3UFD7, Q3ZC80, Q4KLH9, Q6XKD3, Q76JU8, Q76JU9, Q76JV1, Q86VZ1, Q8BUD0, Q8BYC4, Q8HYC3, Q8K3T4, Q8TDS5, Q8TDU9, Q920E0, Q924U0, Q96G91

Diamond homologs: A0A2L0VBG2, E7EM37, E9QJ73, O18821, O18935, O19012, O19014, O19025, O19032, O42329, O62169, O75388, O77700, O77713, O77715, O77721, O77830, O88634, P16395, P30968, P30969, P32236, P32237, P32251, P49651, P49922, P97288, Q01776, Q15722, Q19PY9, Q29003, Q2V2K5, Q6UNA4, Q6XKD3, Q8CH60, Q8JG69, Q8JG70, Q8MJ88, Q8NGA4, Q8SPZ1

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
F2RL3	up-regulates	GNAI1	binding
F2	up-regulates	F2RL3	binding
F2RL3	up-regulates	GNA12	binding
F2RL3	up-regulates	GNA13	binding
F2RL3	“up-regulates activity”	GNAS	binding
F2RL3	“up-regulates activity”	GNAL	binding
F2RL3	“up-regulates activity”	GNAI1	binding
F2RL3	“up-regulates activity”	GNAI3	binding
F2RL3	“up-regulates activity”	GNAO1	binding
F2RL3	“up-regulates activity”	GNAZ	binding
F2RL3	“up-regulates activity”	GNAQ	binding
F2RL3	“up-regulates activity”	GNA14	binding
Thrombin	“up-regulates activity”	F2RL3	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
19:16889296:ATG:A	donor_gain	0.9900
19:16889297:TGGTG:T	donor_loss	0.9900
19:16889299:GTGAG:G	donor_loss	0.9900
19:16889300:T:A	donor_loss	0.9900
19:16889301:GAGTG:G	donor_loss	0.9900
19:16889572:GACA:G	acceptor_gain	0.9900
19:16889295:GATG:G	donor_gain	0.9800
19:16889299:G:GG	donor_gain	0.9800
19:16889571:A:AG	acceptor_gain	0.9800
19:16889572:G:GG	acceptor_gain	0.9800
19:16889291:T:TA	donor_gain	0.9700
19:16889292:G:GA	donor_gain	0.9700
19:16889567:TCCCA:T	acceptor_loss	0.9700
19:16889568:CCCA:C	acceptor_loss	0.9700
19:16889569:CCAGA:C	acceptor_loss	0.9700
19:16889570:CA:C	acceptor_loss	0.9700
19:16889571:A:AT	acceptor_loss	0.9700
19:16889572:GACAG:G	acceptor_loss	0.9700
19:16889287:G:GT	donor_gain	0.9600
19:16889575:A:AG	acceptor_gain	0.9600
19:16889576:G:GG	acceptor_gain	0.9600
19:16889302:AGTGG:A	donor_loss	0.9400
19:16889572:GAC:G	acceptor_gain	0.9400
19:16889576:GC:G	acceptor_gain	0.9400
19:16889576:GCAC:G	acceptor_gain	0.9400
19:16889293:G:GG	donor_gain	0.9300
19:16889297:TG:T	donor_gain	0.9300
19:16889298:GG:G	donor_gain	0.9300
19:16889572:GA:G	acceptor_gain	0.9200
19:16889575:AGCAC:A	acceptor_gain	0.9100

AlphaMissense

2392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:16889974:A:C	S171R	0.986
19:16889976:C:A	S171R	0.986
19:16889976:C:G	S171R	0.986
19:16890436:A:C	S325R	0.986
19:16890438:C:A	S325R	0.986
19:16890438:C:G	S325R	0.986
19:16890448:A:C	S329R	0.984
19:16890450:C:A	S329R	0.984
19:16890450:C:G	S329R	0.984
19:16889889:G:C	W142C	0.982
19:16889889:G:T	W142C	0.982
19:16890196:T:C	F245L	0.978
19:16890198:C:A	F245L	0.978
19:16890198:C:G	F245L	0.978
19:16890460:A:C	S333R	0.978
19:16890462:C:A	S333R	0.978
19:16890462:C:G	S333R	0.978
19:16890502:T:C	F347L	0.978
19:16890504:C:A	F347L	0.978
19:16890504:C:G	F347L	0.978
19:16890358:A:C	S299R	0.975
19:16890360:C:A	S299R	0.975
19:16890360:C:G	S299R	0.975
19:16889887:T:A	W142R	0.973
19:16889887:T:C	W142R	0.973
19:16890145:T:A	C228S	0.972
19:16890146:G:C	C228S	0.972
19:16889814:C:A	N117K	0.966
19:16889814:C:G	N117K	0.966
19:16890115:T:C	F218L	0.957

dbSNP variants (sampled 300 via entrez): RS1000302889 (19:16887762 A>G), RS1000477078 (19:16888671 C>A,G,T), RS1000778813 (19:16887872 G>A), RS1000985112 (19:16891457 G>A), RS1001168161 (19:16890762 G>A), RS1001497038 (19:16887248 G>A,C), RS1001720765 (19:16889093 G>A), RS1002285066 (19:16888055 G>A), RS1003705783 (19:16889382 G>A,C), RS1004480920 (19:16887354 A>C,G), RS1004496884 (19:16892466 T>C), RS1004574288 (19:16887614 G>A), RS1004609946 (19:16891883 A>G), RS1004798871 (19:16891321 G>C), RS1004829616 (19:16889108 G>A)

Disease associations

OMIM: gene MIM:602779 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_141	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010475	deoxycholate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4691 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25 (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
CHEMBL3716552	BMS-986141	2	25

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Proteinase-activated receptors

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
BMS-986120	Antagonist	9.3	pIC50
BMS-986141	Antagonist	9.3	pIC50
UDM-001651	Antagonist	8.62	pIC50
YD-3	Antagonist	6.89	pIC50
ML354	Antagonist	6.85	pIC50

Binding affinities (BindingDB)

966 measured of 968 human assays (968 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(6-fluoro-3-pyridinyl)-4-[[6-methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazole	EC50	0.18 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[2-(2-methylpropyl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.21 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
[4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]phenyl]methanol	EC50	0.23 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-(6-(((6-Methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-yl)oxy)methyl)pyridin-2-yl)-N,N-dimethylbenzamide	IC50	0.23 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-Methoxy-6-(6-methoxy-4-((6-(4-methoxytetrahydro-2H-pyran-4-yl)pyridin-2-yl)methoxy)benzofuran-2-yl)imidazo[2,1-b][1,3,4]thiadiazole	IC50	0.23 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-1,4-oxazepane	EC50	0.24 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[2-(4-methylsulfonylpiperazin-1-yl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.25 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N-methylbenzamide	EC50	0.26 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
(2R,6S)-4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-2,6-dimethylmorpholine	EC50	0.26 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]benzamide	EC50	0.26 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
dicyclopropyl-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]methanol	EC50	0.26 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[2-(4-methyloxan-4-yl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.26 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-2-morpholin-4-yl-1,3-thiazol-5-yl]propan-2-ol	EC50	0.27 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-2,6-dimethyloxan-4-ol	EC50	0.27 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-[4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]oxan-4-yl]-2-methylpropane-2-sulfonamide	EC50	0.27 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-(2-cyanoethyl)-N-ethyl-4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]benzamide	EC50	0.27 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-[4-[[2-(3,4-dihydro-2H-chromen-4-yl)-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	EC50	0.28 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-5-methyl-1,3-thiazol-2-yl]oxan-4-ol	EC50	0.29 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-(4-fluorooxan-4-yl)-4-[[6-methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazole	EC50	0.29 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-5-(trifluoromethyl)-1,3-thiazol-2-yl]morpholine	EC50	0.3 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-tert-butyl-4-[4-[[6-fluoro-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N-methylbenzamide	EC50	0.3 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
8-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-1,4-dioxa-8-azaspiro[4.5]decane	EC50	0.31 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
1-cyclohexyl-1-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]ethanol	EC50	0.31 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-(2-fluoro-4-pyridinyl)-4-[[6-methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)-1-benzofuran-4-yl]oxymethyl]-5-methyl-1,3-thiazole	EC50	0.31 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
(S)-2-(1-Fluoroethyl)-6-(4-((6-(4-fluorotetrahydro-2H-pyran-4-yl)pyridin-2-yl)methoxy)-6-methoxybenzo-furan-2-yl)imidazo[2,1-b][1,3,4]thiadiazole	IC50	0.31 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[(2-phenyl-1,3-thiazol-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.32 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[(2-pyridin-4-yl-1,3-thiazol-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.32 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[5-ethyl-4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]morpholine	EC50	0.32 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
5-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-1,2-oxazole	EC50	0.32 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-[4-[[3-[(3-chlorophenyl)methoxy]phenyl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	IC50	0.32 nM	US-9862730: Imidazothiadiazole derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[2-(3,3,3-trifluoropropyl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.33 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-5-(methoxymethyl)-1,3-thiazol-2-yl]morpholine	EC50	0.33 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-[4-[[2-(4,4-difluorocyclohexyl)-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	EC50	0.33 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]oxan-4-ol	EC50	0.33 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
8-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-8-ol	EC50	0.33 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-[4-[[2-(2-fluoro-4-pyridinyl)-5-propan-2-yl-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	EC50	0.34 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-[4-[[2-(2-fluoro-4-pyridinyl)-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	EC50	0.34 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-[(1S)-1-fluoroethyl]-6-[4-[[2-(4-fluorooxan-4-yl)-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.34 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-[4-[[2-(6-fluoro-3-pyridinyl)-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	EC50	0.35 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-hydroxy-4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]cyclohexan-1-one	EC50	0.35 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
6-(4-((6-(4-Fluorotetrahydro-2H-pyran-4-yl)pyridin-2-yl)methoxy)-6-methoxybenzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	IC50	0.35 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-1,4-thiazinane 1,1-dioxide	EC50	0.36 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
4-[4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]piperazin-1-yl]sulfonylbenzonitrile	EC50	0.36 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
[4-[4-[[6-fluoro-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]phenyl]-pyrrolidin-1-ylmethanone	EC50	0.36 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
N-(cyanomethyl)-4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N-methylbenzamide	EC50	0.36 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[3-(2-propoxypyrimidin-5-yl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	IC50	0.36 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
(S)-2-(1-Fluoroethyl)-6-(6-methoxy-4-((6-(4-methoxytetrahydro-2H-pyran-4-yl)pyridin-2-yl)methoxy)benzofuran-2-yl)imidazo[2,1-b][1,3,4]thiadiazole	IC50	0.36 nM	US-9518064: Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
3-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-oxazol-2-yl]-8-oxa-3-azabicyclo[3.2.1]octane	EC50	0.37 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
2-methoxy-6-[6-methoxy-4-[[2-(1-methylsulfonylpiperidin-4-yl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	EC50	0.37 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation
1-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]cyclohexan-1-ol	EC50	0.37 nM	US-9688695: Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation

ChEMBL bioactivities

2720 potent at pChembl≥5 of 2722 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.64	IC50	0.0229	nM	CHEMBL3715848
10.15	Kd	0.07	nM	CHEMBL3716726
10.07	Kd	0.086	nM	BMS-986141
10.01	Kd	0.098	nM	CHEMBL3716726
10.00	Kd	0.1	nM	BMS-986141
9.74	EC50	0.18	nM	CHEMBL3715479
9.70	IC50	0.2	nM	CHEMBL3716230
9.68	EC50	0.21	nM	CHEMBL3718225
9.68	EC50	0.21	nM	CHEMBL6056014
9.64	EC50	0.23	nM	CHEMBL3716420
9.64	IC50	0.23	nM	CHEMBL3715013
9.64	IC50	0.23	nM	CHEMBL3716902
9.62	EC50	0.24	nM	CHEMBL3716230
9.60	EC50	0.25	nM	CHEMBL3717127
9.59	EC50	0.26	nM	CHEMBL3718763
9.59	EC50	0.26	nM	CHEMBL3717042
9.59	EC50	0.26	nM	CHEMBL3717235
9.59	EC50	0.26	nM	CHEMBL3717808
9.59	EC50	0.26	nM	CHEMBL3715840
9.57	EC50	0.27	nM	CHEMBL3718631
9.57	EC50	0.27	nM	CHEMBL3716142
9.57	EC50	0.27	nM	CHEMBL3718707
9.57	EC50	0.27	nM	CHEMBL3717618
9.55	EC50	0.28	nM	CHEMBL3717706
9.54	EC50	0.29	nM	CHEMBL3715442
9.54	EC50	0.29	nM	CHEMBL3716059
9.54	IC50	0.29	nM	CHEMBL3717308
9.52	EC50	0.3	nM	CHEMBL3715043
9.52	EC50	0.3	nM	CHEMBL3717937
9.52	IC50	0.3	nM	CHEMBL3715848
9.52	IC50	0.3	nM	CHEMBL3718639
9.52	IC50	0.3	nM	CHEMBL3717937
9.52	IC50	0.3	nM	CHEMBL3717235
9.51	EC50	0.31	nM	CHEMBL3718801
9.51	EC50	0.31	nM	CHEMBL3715853
9.51	EC50	0.31	nM	CHEMBL3714842
9.51	IC50	0.31	nM	CHEMBL3718355
9.49	EC50	0.32	nM	CHEMBL3717419
9.49	EC50	0.32	nM	CHEMBL3718267
9.49	EC50	0.32	nM	CHEMBL3717956
9.49	EC50	0.32	nM	CHEMBL3716160
9.49	EC50	0.32	nM	CHEMBL3715848
9.49	IC50	0.32	nM	CHEMBL3732089

PubChem BioAssay actives

323 with measured affinity, of 539 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
2-methoxy-6-[6-methoxy-4-[(2-phenyl-1,3-thiazol-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1324436: Antagonist activity at PAR4 (unknown origin) assessed as inhibition of activating peptide-induced receptor activation	ic50	<0.0001	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N,N-dimethylbenzamide	1892454: Binding affinity to PAR4 (unknown origin) assessed as saturation binding	kd	0.0001	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-5-methyl-1,3-thiazol-2-yl]morpholine	1892454: Binding affinity to PAR4 (unknown origin) assessed as saturation binding	kd	0.0001	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-1,4-oxazepane	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0002	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-5-(trifluoromethyl)-1,3-thiazol-2-yl]morpholine	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0003	uM
6-[4-[[2-(4,4-difluorocyclohexyl)-1,3-thiazol-4-yl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0003	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]benzamide	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0003	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-5-methyl-1,3-thiazol-2-yl]-N,N-dimethylbenzamide	1727512: Inhibition of human PAR4 expressed in HEK293 cells assessed as Ala-(L-4-F-Phe)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-induced inhibition of calcium mobilization preincubated for 30 mins followed by Ala-(L-4-F-Phe)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly stimulation by FLIPR method	ic50	0.0004	uM
2-methoxy-6-[6-methoxy-4-[(2-propyl-1,3-thiazol-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0004	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]pyrimidin-2-yl]morpholine	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0004	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N-methylbenzamide	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0004	uM
2-methoxy-6-[6-methoxy-4-[(2-piperidin-1-yl-1,3-thiazol-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0004	uM
2-methoxy-6-[6-methoxy-4-[(2-propan-2-yl-1,3-thiazol-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0005	uM
2-methoxy-6-[6-methoxy-4-[[2-(thian-4-yl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0005	uM
6-[3-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]phenyl]pyridine-3-carbonitrile	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0005	uM
8-(4-chloro-6-methoxy-1,3-benzothiazol-2-yl)-3,6-dimethylquinazolin-4-one	1784082: Antagonist activity at human PAR4 expressed in Ga15-HEK293 cells assessed as reduction in PAR4 AP AYPGKF-NH2-induced cytosolic calcium incubated for 24 hrs by FLIPR - calcium mobilization assay	ic50	0.0005	uM
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	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0005	uM
2-methoxy-6-[6-methoxy-4-[[3-(6-methoxy-3-pyridinyl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0005	uM
(3,3-difluoropyrrolidin-1-yl)-[4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]phenyl]methanone	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
4-[6-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-2-pyridinyl]morpholine	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
2-methoxy-6-[6-methoxy-4-[[3-methoxy-5-(trifluoromethyl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
3-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-8-oxa-3-azabicyclo[3.2.1]octane	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-oxazol-2-yl]morpholine	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]morpholine	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
6-[4-[(2-ethyl-1,3-thiazol-4-yl)methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
[4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]phenyl]-pyrrolidin-1-ylmethanone	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
2-methoxy-6-[6-methoxy-4-[[3-[5-(trifluoromethyl)-2-pyridinyl]phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0006	uM
4-[3-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]phenyl]morpholine	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0007	uM
2-methoxy-6-[6-methoxy-4-[[3-(2-methoxypyrimidin-5-yl)phenyl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0007	uM
2-methoxy-6-[6-methoxy-4-[[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0007	uM
3-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N,N-dimethylbenzamide	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0008	uM
2-methoxy-6-[6-methoxy-4-[[2-(4-methylsulfonylphenyl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0008	uM
N-[2-[[2-[2-(methoxymethyl)-7-methylquinoxalin-5-yl]-4-methyl-1,3-benzothiazol-6-yl]oxy]ethyl]benzenesulfonamide	2090462: Antagonist activity at full length human PAR4 expressed in HEK293 cells measured after 30 mins by FLIPR calcium mobilization assay	ic50	0.0008	uM
2-methoxy-6-[6-methoxy-4-(2-phenoxyethoxy)-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0008	uM
2-methoxy-6-[6-methoxy-4-[[2-(6-methoxy-3-pyridinyl)-1,3-thiazol-4-yl]methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0008	uM
6-[4-[[3-(furan-3-yl)phenyl]methoxy]-6-methoxy-1-benzofuran-2-yl]-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0008	uM
2-methoxy-6-[6-methoxy-4-[(3-phenylsulfanylphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0009	uM
2-methoxy-6-[6-methoxy-4-[(2-phenylpyrimidin-4-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0009	uM
6-(4,6-dimethoxy-1-benzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0010	uM
3-[2-[2-(difluoromethoxy)-7-methylquinoxalin-5-yl]-4-methyl-1,3-thiazol-5-yl]phenol	1727512: Inhibition of human PAR4 expressed in HEK293 cells assessed as Ala-(L-4-F-Phe)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-induced inhibition of calcium mobilization preincubated for 30 mins followed by Ala-(L-4-F-Phe)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly stimulation by FLIPR method	ic50	0.0010	uM
3-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]benzonitrile	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0010	uM
2-methoxy-6-[6-methoxy-4-(2-phenylethoxy)-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0011	uM
2-methoxy-6-[6-methoxy-4-[(3-pyrimidin-5-ylphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0011	uM
2-methoxy-6-[6-methoxy-4-[(4-phenyl-1,3-thiazol-2-yl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0011	uM
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]benzoic acid	1892446: Antagonist activity at full length human PAR4 expressed in HEK293 cells assessed as reduction in H-Ala-Phe(4-F)-Pro-Gly-Trp-Leu-Val-Lys-Asn-Gly-NH2 induced intracellular calcium mobilization pretreated with compound for 30 mins followed by agonist addition for 30 mins by FLIPR method	ic50	0.0011	uM
2-methoxy-6-(6-methoxy-1-benzofuran-2-yl)imidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0012	uM
[(7R)-2-(2-methoxy-7-methylquinoxalin-5-yl)-7,8-dihydrofuro[2,3-g][1,3]benzothiazol-7-yl]methyl N-(2-methylpyrimidin-5-yl)carbamate	2090462: Antagonist activity at full length human PAR4 expressed in HEK293 cells measured after 30 mins by FLIPR calcium mobilization assay	ic50	0.0012	uM
2-methoxy-6-[6-methoxy-4-[(3-phenoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0012	uM
N-[2-[[4-chloro-2-(3,6-dimethyl-4-oxoquinazolin-8-yl)-1,3-benzothiazol-6-yl]oxy]ethyl]-4-(trifluoromethyl)benzenesulfonamide	1784082: Antagonist activity at human PAR4 expressed in Ga15-HEK293 cells assessed as reduction in PAR4 AP AYPGKF-NH2-induced cytosolic calcium incubated for 24 hrs by FLIPR - calcium mobilization assay	ic50	0.0012	uM
2-methoxy-6-[6-methoxy-4-[(4-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole	1607802: Antagonist activity at full-length human PAR4 expressed in HEK293 cells assessed as inhibition of AYPGKF-induced intracellular calcium mobilization preincubated for 30 mins followed by AYPGKF addition and measured by calcium indicator-based FLIPR assay	ic50	0.0013	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases methylation, increases expression, increases methylation	4
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
zinc chromate	decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
fluorene	decreases methylation	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bivalirudin	decreases activity	1
chromium hexavalent ion	decreases expression, increases abundance	1
alanyl-tyrosyl-prolyl-glycyl-lysyl-phenylalanine	increases activity, increases uptake, affects binding	1
GYPGKF-NH(2)	increases chemical synthesis, affects binding, decreases reaction, increases activity	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	affects methylation	1
Calcium	affects binding, increases activity, increases uptake	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects binding, decreases reaction, increases activity, increases chemical synthesis	1
Smoke	increases expression	1
Thrombin	affects binding, increases activity	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

84 unique, capped per target: 56 binding, 28 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1061659	Functional	Antagonist activity at PAR4 expressed in Cos7 cells assessed as AYPGKF-mediated SRE-luciferase activity	Discovery of novel protease activated receptors 1 antagonists with potent antithrombotic activity in vivo. — J Med Chem
CHEMBL3390699	Binding	Antagonist activity at PAR4 in PAR-4-AP-stimulated human platelets compound pretreated for 5 mins by fluorescent PAC1 integrin alpha2bb3 activation assay	Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0U4	Ubigene Hep G2 F2RL3 KO	Cancer cell line	Male
CVCL_H494	CHO-K1/PAR4	Spontaneously immortalized cell line	Female
CVCL_KX03	PathHunter CHO-K1 F2RL3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA29	PathHunter U2OS F2RL3 Activated GPCR Internalization	Cancer cell line	Female

Clinical trials (associated diseases)

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