F2RL1

Summary

F2RL1 (F2R like trypsin receptor 1, HGNC:3538) is a protein-coding gene on chromosome 5q13.3, encoding Proteinase-activated receptor 2 (P55085). Receptor for trypsin and trypsin-like enzymes coupled to G proteins.

This gene encodes a member of the G-protein coupled receptor 1 family of proteins. The encoded cell surface receptor is activated through proteolytic cleavage of its extracellular amino terminus, resulting in a new amino terminus that acts as a tethered ligand that binds to an extracellular loop domain. Activation of the receptor has been shown to stimulate vascular smooth muscle relaxation, dilate blood vessels, increase blood flow, and lower blood pressure. This protein is also important in the inflammatory response, as well as innate and adaptive immunity.

Source: NCBI Gene 2150 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 51 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Transcription factor: yes — 19 downstream targets (CollecTRI)
• MANE Select transcript: NM_005242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3538
Approved symbol	F2RL1
Name	F2R like trypsin receptor 1
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Aliases	PAR2
Ensembl gene	ENSG00000164251
Ensembl biotype	protein_coding
OMIM	600933
Entrez	2150

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000296677, ENST00000514165

RefSeq mRNA: 1 — MANE Select: NM_005242 NM_005242

CCDS: CCDS4033

Canonical transcript exons

ENST00000296677 — 2 exons

Exon	Start	End
ENSE00001082780	76832690	76835315
ENSE00001169714	76819030	76819264

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2007 / max 505.0893, expressed in 917 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57154	5.5972	839
57155	3.9941	696
57156	0.6095	280

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	99.07	gold quality
colonic mucosa	UBERON:0000317	98.92	gold quality
jejunal mucosa	UBERON:0000399	98.62	gold quality
upper leg skin	UBERON:0004262	97.19	gold quality
duodenum	UBERON:0002114	95.93	gold quality
nephron tubule	UBERON:0001231	95.18	gold quality
rectum	UBERON:0001052	95.11	gold quality
skin of hip	UBERON:0001554	94.30	gold quality
gingival epithelium	UBERON:0001949	94.26	gold quality
ileal mucosa	UBERON:0000331	94.20	gold quality
gingiva	UBERON:0001828	93.31	gold quality
mucosa of transverse colon	UBERON:0004991	92.94	gold quality
choroid plexus epithelium	UBERON:0003911	92.76	gold quality
islet of Langerhans	UBERON:0000006	92.50	gold quality
nipple	UBERON:0002030	92.14	gold quality
upper arm skin	UBERON:0004263	92.12	gold quality
caput epididymis	UBERON:0004358	91.68	gold quality
seminal vesicle	UBERON:0000998	91.11	gold quality
penis	UBERON:0000989	91.09	gold quality
mammalian vulva	UBERON:0000997	91.01	gold quality
renal medulla	UBERON:0000362	90.27	gold quality
skin of abdomen	UBERON:0001416	90.26	gold quality
gall bladder	UBERON:0002110	90.13	gold quality
kidney epithelium	UBERON:0004819	89.80	gold quality
epithelial cell of pancreas	CL:0000083	89.75	gold quality
zone of skin	UBERON:0000014	89.32	gold quality
esophagus squamous epithelium	UBERON:0006920	88.85	gold quality
pancreatic ductal cell	CL:0002079	88.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.53	gold quality
squamous epithelium	UBERON:0006914	88.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

19 targets.

Target	Regulation
AREG	Activation
CD44	Activation
CORO1C	Activation
CTSD	Repression
DUSP6	Activation
F2RL1	Activation
FOSL1	Activation
ITGB4	Repression
KLF6	Activation
MSC	Repression
RAB3A	Activation
RARG	Repression
SDC4	Activation
SERPINB2	Activation
THBS1	Activation
TNFRSF12A	Activation
TSPAN15	Repression
TXNIP	Repression
WWOX	Activation

Upstream regulators (CollecTRI, top): F2RL1

miRNA regulators (miRDB)

69 targeting F2RL1, 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-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4420	99.82	70.08	1624

Literature-anchored findings (GeneRIF, showing 40)

• upregulation of PAR-2 in respiratory epithelium of asthmatics (PMID:11692107)
• Purified human eosinophils express functional PAR2 and are activated by serine proteases (e.g., trypsin) through this receptor. (PMID:11714832)
• When expressed in respiratory epithelial cells and cell lines, protease-activated receptor 2 (PAR2) induces the release of IL-6, IL-8, and PGE2. (PMID:11907122)
• Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2. (PMID:12123809)
• Stimulation of PAR2 in colon mucosa significantly enhanced ion transport. This increase is dependent on the increase in intracellular Ca2+. (PMID:12139406)
• We conclude that hPAR(2) N-linked glycosylation and sialylation regulates receptor expression and/or signalling (PMID:12171601)
• Both PAR1 and PAR2 upregulate COX-2, but not COX-1, expression in HUVEC cells (PMID:12195707)
• Proinflammatory cytokine release from respiratory epithelial cells in response to activated house dust mite allergen Der p 1 involves activation of PAR2. (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)
• PAR2 in SMCs of the human coronary arteries plays a crucial role in the cell migration induced by TF/FVIIa complex (PMID:12479889)
• PAR-2 expression was higher in pancreatic cancers with infiltrative growth pattern than in those with expansive growth pattern and in those with severe fibrosis. PAR-2 is involved in cancer invasion & the induction of fibrosis in human pancreatic cancer. (PMID:12527925)
• PAR2 is a primary mediator of RhoA activation, signaling, and cytoskeletal reorganization when expressed on LNCaP prostate cancer cells. (PMID:12534282)
• Expression of wild-type rab11a accelerated recovery of PAR2 at cell surface and resensitization of PAR2 signaling. rab5a required for PAR2 endocytosis and resensitization; rab11a contributes to trafficking of PAR2 from Golgi apparatus to plasma membrane. (PMID:12540381)
• HAT regulates cellular functions of human bronchial epithelial cells via activation of protease-activated receptor-2. (PMID:12630574)
• trypsin induces PGE2 release and COX-2 in human airway smooth muscle cells in asthma, which is unlikely to be via PAR-2 activation. (PMID:12754192)
• Protease-activated receptor-2 expression is activated by trypsin in human pancreatic cancers (PMID:12792776)
• differentiation of human monocytes is associated with differential expression of functionally active PARs that mediate distinct regulatory functions in inflammation and atherogenesis. (PMID:12805069)
• trypsin and PAR2 modulate eosinophil functions, including shape change, release of cysteinyl leukotrienes, and generation of reactive oxygen species (PMID:12832443)
• The endogenous PAR-2 agonist tryptase was increased in atopic dermatitis (AD) patients. PAR-2 was enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists enhanced itching (PMID:12867500)
• -2 expressed by renal resident cells and activated by either mast cell tryptase or FXa may induce extracellular matrix deposition modifying the PAI-1/PA balance and inducing TGF-beta expression (PMID:12874461)
• proteinase-activated receptor-2 mediated phagocytosis is Rho dependent and proteinase-activated receptor-2 signals to Rho and cAMP in keratinocytes (PMID:12925212)
• findings support a role for PAR1, and potentially PAR2 and PAR3 in the invasive phase of human placentation (PMID:14507634)
• Proinflammatory role of proteinase-activated receptor-2 in dermatitis. (PMID:14519665)
• In the gastric mucosa, PAR-2 modulates multiple functions and exerts mucosal cytoprotection mainly by activating sensory neurons, as discussed in this review. (PMID:14585156)
• proteases in cockroach extract activate par-2 in human bronchial eptihelail cells which then induces Il-8 expression (PMID:14657869)
• The agonists of PAR-2 and trypsin are potent secretagogues of human colon mast cells, which are likely to contribute to the development of inflammatory disorders in human gut. (PMID:14760751)
• activated by German cockroach extract in human bronchi epithelial cell line, and genetrating calcium oscillations by releasing calcium from thapsigargin sensitive calcium stores. (PMID:14767448)
• signaling pathways downstream of PAR2 activation that lead to colon cancer cell proliferation in a cancer colon cell line. (PMID:15010475)
• Human airway trypsin-like protease might promote PAR-2-mediated IL-8 production to accumulate inflammatory cells in the epidermal layer of psoriasis (PMID:15102084)
• PAR-2 mediates cutaneous pigmentation both through increased uptake of melanosomes by keratinocytes, as well as by release of PGE(2) and PGF(2alpha) (PMID:15140225)
• data confirm a role for PAR1 in migration and metastasis and demonstrate an unexpected role for PAR2 in thrombin-dependent tumor cell migration and in metastasis (PMID:15280447)
• Diverse functions of arrestins in regulating PAR2 signaling and trafficking. (PMID:15475570)
• the degree of fibroblast proliferation, attenuated by extracellular matrix and upregulated by growth factors, influences whether fibroblasts express PAR-2 (PMID:15482468)
• protease-activated receptor-2-mediated migration of tumor cells requires both beta-arrestin-1 and -2 (PMID:15489220)
• Increased expression of protease-activated receptor 2 is associated with papillary adenocarcinoma of the gallbladder (PMID:15492786)
• present study describes how TMPRSS2 may contribute to prostate tumour metastasis via the activation of PAR-2 (PMID:15537383)
• possible involvement of PAR2 in menstruation and other architectural changes of the endometrium occurring during the menstrual cycle (PMID:15585570)
• PAR2 may play an important regulatory role of human keratinocytes during inflammation and immune response. (PMID:15654951)
• analysis of PAR1 cleavage and signaling in response to activated protein C and thrombin (PMID:15665002)
• results provide further evidence for a role of protease-activated receptor 2(PAR-2) in inflammatory airway disease (PMID:15809358)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	f2rl1.1	ENSDARG00000068856
danio_rerio	f2rl1.2	ENSDARG00000077540
mus_musculus	F2rl1	ENSMUSG00000021678
rattus_norvegicus	F2rl1	ENSRNOG00000018003

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

Proteinase-activated receptor 2 — P55085 (reviewed: P55085)

Alternative names: Coagulation factor II receptor-like 1, G-protein coupled receptor 11, Thrombin receptor-like 1

All UniProt accessions (2): D6RJH3, P55085

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3. Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o)-alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at ‘Ser-536’; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as pro-inflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders. Probably mediates activation of pro-inflammatory and pro-fibrotic responses in fibroblasts, triggered by coagulation factor Xa (F10). Mediates activation of barrier protective signaling responses in endothelial cells, triggered by coagulation factor Xa (F10).

Subunit / interactions. Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed in tissues with especially high levels in pancreas, liver, kidney, small intestine, and colon. Moderate expression is detected in many organs, but none in brain or skeletal muscle. Expressed in endothelial cells.

Post-translational modifications. A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Activating serine proteases include trypsin, mast cell tryptase, GZMK, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine protease 1/ST14. Subsequent cleavage by serine proteases, including neutrophil elastase and cathepsin G, leads to receptor deactivation. At least in part, implicated proteases are also shown to activate the receptor; the glycosylation status of the receptor is thought to contribute to the difference. In addition to conventional trypsin-like proteases activated by other proteases and glycosidases derived from bacteria, fungi and insects. Activated by serine protease allergens such as dust mite Der p3 and Der p9 and mold Pen c13. Activated by P.gingivalis arginine-specific (trypsin-like) cysteine proteinases called gingipains. Activated by S.griseus exogenous chitinase. Activated by A.alternata aspartate protease; the cleavage generates non-conventional processed forms. Proteolytically cleaved by coagulation factor Xa (F10); cleavage results in activation of F2RL1-dependent signaling. N-glycosylated and sialylated. Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin. Monoubiquitinated by CBL at the plasma membrane and in early endosomes; not required for receptor endocytosis but for translocation to late endosomes or lysosomes. Deubiquitination involves STAMBP and USP8; required for lysosomal trafficking and receptor degradation.

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

Miscellaneous. Synthetic PAR agonist peptides (APs) that mimic the first six amino acids of the newly formed N-terminus activate the native, uncleaved receptor nonenzymatically by binding directly to the corresponding second extracellular loop to mediate signaling.

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

RefSeq proteins (1): NP_005233* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002281	Pro_rcpt_2	Family
IPR003912	Protea_act_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (69 total): helix 17, mutagenesis site 16, topological domain 8, transmembrane region 7, sequence variant 4, chain 3, glycosylation site 2, sequence conflict 2, strand 2, signal peptide 1, propeptide 1, region of interest 1, compositionally biased region 1, site 1, lipid moiety-binding region 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5NDD	X-RAY DIFFRACTION	2.8
9D0A	ELECTRON MICROSCOPY	3.1
9E7R	ELECTRON MICROSCOPY	3.18
8ZME	ELECTRON MICROSCOPY	3.2
8ZMD	ELECTRON MICROSCOPY	3.25
5NDZ	X-RAY DIFFRACTION	3.6
5NJ6	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55085-F1	82.92	0.55

Antibody-complex structures (SAbDab): 3 — 5NJ6, 8ZME, 9D0A

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): 36–37 (cleavage; by trypsin and gzmk)

Post-translational modifications (1): 361

Disulfide bonds (1): 148–226

Glycosylation sites (2): 30, 222

Mutagenesis-validated functional residues (16):

Position	Phenotype
30	increases sensitivity towards tryptase. decreases cell surface expression; when associated with a-222.
36	abolished and activation cleavage by gzmk.
135	slight reduction in ligand-mediated receptor activation.
154	severe reduction in ligand-mediated receptor activation.
157	severe reduction in ligand-mediated receptor activation.
210	no defect in ligand-mediated receptor activation.
222	decreases cell surface expression; when associated with a-30. loss of sensitivity towards all tested proteases.
222	no defect in ligand-mediated receptor activation.
227	no defect in ligand-mediated receptor activation.
227	slight reduction in ligand-mediated receptor activation.
228	severe reduction in ligand-mediated receptor activation.
327	slight reduction in ligand-mediated receptor activation.
355–363	abolishes signaling through accumulation of intracellular calcium and phosphoinositide; no effect in signaling through m
361	loss of palmitoylation; increases surface expression and internalization following trypsin activation, decreases sensiti
363	reduces receptor desensitization and internalization, activates erk1/2; when associated with a-366.
366	reduces receptor desensitization and internalization, activates erk1/2; when associated with a-363.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 581 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_EPITHELIUM_DEVELOPMENT, BROWNE_HCMV_INFECTION_6HR_DN, WANG_CLIM2_TARGETS_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, BOYAULT_LIVER_CANCER_SUBCLASS_G56_DN, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (56): T cell activation involved in immune response (GO:0002286), positive regulation of leukocyte chemotaxis (GO:0002690), positive regulation of cytokine production involved in immune response (GO:0002720), positive regulation of glomerular filtration (GO:0003104), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), blood coagulation (GO:0007596), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), regulation of blood coagulation (GO:0030193), positive regulation of cell migration (GO:0030335), positive regulation of actin filament depolymerization (GO:0030836), positive regulation of pseudopodium assembly (GO:0031274), negative regulation of chemokine production (GO:0032682), positive regulation of chemokine production (GO:0032722), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of superoxide anion generation (GO:0032930), positive regulation of toll-like receptor 2 signaling pathway (GO:0034137), negative regulation of toll-like receptor 3 signaling pathway (GO:0034140), positive regulation of toll-like receptor 3 signaling pathway (GO:0034141), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), positive regulation of Rho protein signal transduction (GO:0035025), neutrophil activation (GO:0042119), vasodilation (GO:0042311), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of eosinophil degranulation (GO:0043311), positive regulation of GTPase activity (GO:0043547), innate immune response (GO:0045087), cell-cell junction maintenance (GO:0045217), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of JNK cascade (GO:0046328), negative regulation of JNK cascade (GO:0046329), positive regulation of JNK cascade (GO:0046330), negative regulation of insulin secretion (GO:0046676), leukocyte migration (GO:0050900)

GO Molecular Function (9): G-protein alpha-subunit binding (GO:0001965), protease binding (GO:0002020), 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), signaling receptor activity (GO:0038023), proteinase-activated receptor activity (GO:0001648), protein binding (GO:0005515)

GO Cellular Component (5): early endosome (GO:0005769), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), pseudopodium (GO:0031143), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	6
protein binding	3
chemokine production	2
regulation of chemokine production	2
lymphocyte activation involved in immune response	1
immune response	1
T cell activation	1
positive regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
leukocyte chemotaxis	1
positive regulation of chemotaxis	1
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
regulation of glomerular filtration	1
glomerular filtration	1
positive regulation of multicellular organismal process	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological quality	1
hemostasis	1
wound healing	1
coagulation	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
blood coagulation	1
regulation of response to external stimulus	1
regulation of coagulation	1
regulation of wound healing	1
regulation of hemostasis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin filament depolymerization	1
regulation of actin filament depolymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of protein depolymerization	1
positive regulation of supramolecular fiber organization	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F2RL1	S1PR1	P21453	786
F2RL1	TRPA1	O75762	779
F2RL1	S1PR3	Q99500	732
F2RL1	SPHK1	Q9NYA1	728
F2RL1	PITRM1	Q5JRX3	724
F2RL1	SPHK2	Q9NRA0	715
F2RL1	GNAQ	P50148	688
F2RL1	PROCR	Q9UNN8	653
F2RL1	F3	P13726	608
F2RL1	EPRS1	P07814	570
F2RL1	ARRB1	P49407	563
F2RL1	ARRB2	P32121	561
F2RL1	TRPV1	Q8NER1	548
F2RL1	HP	P00737	524
F2RL1	GNA12	Q03113	495

IntAct

127 interactions, top by confidence:

A	B	Type	Score
F2RL1	TMED2	psi-mi:“MI:0915”(physical association)	0.700
TMED2	F2RL1	psi-mi:“MI:0403”(colocalization)	0.700
TMED2	F2RL1	psi-mi:“MI:0915”(physical association)	0.700
COPS5	F2RL1	psi-mi:“MI:0915”(physical association)	0.640
F2RL1	COPS5	psi-mi:“MI:0915”(physical association)	0.640
F2RL1	COPS5	psi-mi:“MI:0403”(colocalization)	0.640
COPS5	F2RL1	psi-mi:“MI:0403”(colocalization)	0.640
Arrb1	F2RL1	psi-mi:“MI:0403”(colocalization)	0.600
Arrb1	F2RL1	psi-mi:“MI:0915”(physical association)	0.600
F2RL1	CBL	psi-mi:“MI:0403”(colocalization)	0.560
F2RL1	CBL	psi-mi:“MI:0915”(physical association)	0.560
CBL	F2RL1	psi-mi:“MI:0915”(physical association)	0.560
PRNP	F2RL1	psi-mi:“MI:0915”(physical association)	0.550
PRNP	F2RL1	psi-mi:“MI:2364”(proximity)	0.550
PTDSS2	F2RL1	psi-mi:“MI:0915”(physical association)	0.550
Arrb1	Raf1	psi-mi:“MI:0403”(colocalization)	0.540
Arrb1	Raf1	psi-mi:“MI:0915”(physical association)	0.540
Arrb1	Raf1	psi-mi:“MI:0914”(association)	0.540
	UBXN8	psi-mi:“MI:0914”(association)	0.530
OGFOD3	CLGN	psi-mi:“MI:0914”(association)	0.530

BioGRID (196): F2RL1 (Affinity Capture-RNA), GEMIN4 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), SLMAP (Affinity Capture-MS), RINT1 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), F2RL1 (Reconstituted Complex), SLMAP (Affinity Capture-MS), HSDL2 (Affinity Capture-MS), INTS12 (Affinity Capture-MS), C19orf25 (Affinity Capture-MS), F2RL1 (Two-hybrid), F2RL1 (Affinity Capture-MS), F2RL1 (Proximity Label-MS), HSPA1B (Affinity Capture-Western)

ESM2 similar proteins: A7YY44, B0UXR0, B5X337, E7FEL0, O00254, O08675, O14843, O15529, O15552, O46685, P25116, P26824, P30558, P34996, P46093, P47749, P47900, P48042, P49650, P49651, P49652, P50132, P55085, P55086, P56488, P59902, Q00991, Q09QM4, Q13304, Q15743, Q1JQB3, Q2HJA4, Q3UFD7, Q4KLH9, Q58D85, Q63645, Q76EI6, Q86VZ1, Q8BFQ3, Q8BLG2

Diamond homologs: A1ZAX0, B2ZI34, E7F7V7, F1MV99, F1R332, O08726, O08786, O43603, O54798, O54799, O62709, O88626, O88854, O97666, O97772, O97967, P05363, P08911, P08912, P21451, P21729, P22270, P24053, P24530, P25101, P26684, P28088, P28336, P28646, P30550, P30551, P30552, P30553, P30796, P30872, P30873, P30937, P30974, P31391, P32238

SIGNOR signaling

61 interactions.

A	Effect	B	Mechanism
F2	up-regulates	F2RL1	binding
F2RL1	“up-regulates quantity by expression”	RAB3A	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	TNFRSF12A	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	CORO1C	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	F2RL1	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	KLF6	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	THBS1	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	CD44	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	SDC4	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	DUSP6	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	WWOX	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	AREG	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	SERPINB2	“transcriptional regulation”
F2RL1	“down-regulates quantity by repression”	TXNIP	“transcriptional regulation”
F2RL1	“down-regulates quantity by repression”	RARG	“transcriptional regulation”
F2RL1	“down-regulates quantity by repression”	ITGB4	“transcriptional regulation”
F2RL1	“down-regulates quantity by repression”	CTSD	“transcriptional regulation”
F2RL1	“down-regulates quantity by repression”	MSC	“transcriptional regulation”
F2RL1	“down-regulates quantity by repression”	TSPAN15	“transcriptional regulation”
F2RL1	“up-regulates activity”	GNAS	binding
F2RL1	“up-regulates activity”	GNAI1	binding
F2RL1	“up-regulates activity”	GNAI3	binding
F2RL1	“up-regulates activity”	GNAO1	binding
F2RL1	“up-regulates activity”	GNAZ	binding
F2RL1	“up-regulates activity”	GNAQ	binding
F2RL1	“up-regulates activity”	GNA14	binding
F2RL1	“up-regulates activity”	GNA15	binding
“PAR-1 (Protease-Activated Receptor) Selective Activating Peptide”	“up-regulates activity”	F2RL1	“chemical activation”
N-[(2S)-1-[[(2S)-1-[[3-[4-(Aminomethyl)piperidine-1-carbonyl]phenyl]methylamino]-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	“down-regulates activity”	F2RL1	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ion transport by P-type ATPases	5	15.7×	2e-03
Ion homeostasis	5	15.4×	2e-03
Cardiac conduction	6	9.9×	3e-03
Ion channel transport	6	8.7×	4e-03
Muscle contraction	6	7.0×	8e-03
Transport of small molecules	13	5.0×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
calcium ion transport	6	11.4×	3e-03
protein localization to plasma membrane	8	9.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

321 predictions. Top by Δscore:

Variant	Effect	Δscore
5:76832686:A:AG	acceptor_gain	1.0000
5:76832686:ACAG:A	acceptor_gain	1.0000
5:76832687:CAGGA:C	acceptor_loss	1.0000
5:76832688:A:AC	acceptor_loss	1.0000
5:76832688:A:AG	acceptor_gain	1.0000
5:76832689:G:GG	acceptor_gain	1.0000
5:76832689:GGA:G	acceptor_gain	1.0000
5:76819260:CCAAG:C	donor_loss	0.9900
5:76819261:CAAG:C	donor_loss	0.9900
5:76819263:AGGT:A	donor_loss	0.9900
5:76819265:G:A	donor_loss	0.9900
5:76819266:T:A	donor_loss	0.9900
5:76832683:T:A	acceptor_gain	0.9900
5:76832687:C:G	acceptor_gain	0.9900
5:76832688:AG:A	acceptor_gain	0.9900
5:76832689:GG:G	acceptor_gain	0.9900
5:76832689:GGAA:G	acceptor_gain	0.9900
5:76832689:GGAAC:G	acceptor_gain	0.9800
5:76832687:CAGG:C	acceptor_gain	0.9600
5:76832688:AGG:A	acceptor_gain	0.9600
5:76819265:G:GG	donor_gain	0.9500
5:76832685:TACA:T	acceptor_gain	0.9500
5:76832686:ACAGG:A	acceptor_gain	0.9200
5:76832689:G:T	acceptor_gain	0.9200
5:76820513:AAT:A	acceptor_gain	0.8300
5:76820512:TAA:T	acceptor_gain	0.8200
5:76820198:G:GT	donor_gain	0.8000
5:76820485:GTGC:G	acceptor_gain	0.8000
5:76832684:GTACA:G	acceptor_gain	0.8000
5:76820318:G:GT	donor_gain	0.7300

AlphaMissense

2589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:76833030:G:C	W141C	0.996
5:76833030:G:T	W141C	0.996
5:76833505:T:C	F300L	0.995
5:76833507:C:A	F300L	0.995
5:76833507:C:G	F300L	0.995
5:76833028:T:A	W141R	0.994
5:76833028:T:C	W141R	0.994
5:76833050:G:A	C148Y	0.994
5:76833115:A:C	S170R	0.994
5:76833117:T:A	S170R	0.994
5:76833117:T:G	S170R	0.994
5:76833202:T:A	W199R	0.993
5:76833202:T:C	W199R	0.993
5:76833514:A:C	S303R	0.993
5:76833516:T:A	S303R	0.993
5:76833516:T:G	S303R	0.993
5:76833049:T:A	C148S	0.992
5:76833050:G:C	C148S	0.992
5:76833051:T:G	C148W	0.992
5:76833283:T:A	C226S	0.992
5:76833284:G:A	C226Y	0.992
5:76833284:G:C	C226S	0.992
5:76833285:T:G	C226W	0.991
5:76833283:T:C	C226R	0.990
5:76833502:T:C	C299R	0.990
5:76833050:G:T	C148F	0.989
5:76833358:T:C	F251L	0.989
5:76833360:T:A	F251L	0.989
5:76833360:T:G	F251L	0.989
5:76833616:A:C	S337R	0.989

dbSNP variants (sampled 300 via entrez): RS1000180334 (5:76824069 C>T), RS1000195683 (5:76823898 T>C), RS1000209871 (5:76818140 G>A,T), RS1000396757 (5:76818727 G>T), RS1000459569 (5:76823155 G>A), RS1000661398 (5:76830363 C>A,T), RS1001060023 (5:76829177 A>G), RS1001143627 (5:76817239 G>T), RS1001215504 (5:76823539 C>T), RS1001326365 (5:76826939 C>A,G), RS1001336481 (5:76827182 A>G), RS1001344249 (5:76827956 C>T), RS1001491553 (5:76834461 G>A), RS1001582364 (5:76833569 A>C,G), RS1001793746 (5:76827608 T>TC)

Disease associations

OMIM: gene MIM:600933 | 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
GCST007016_5	Serum bilirubin levels x sex interaction in metabolic syndrome	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5963 (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: 258 (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
CHEMBL463763	TRIPTOLIDE	3	258

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2243057	F2RL1		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 (17 total), top 17:

Ligand	Action	Affinity	Parameter
Isox-Cha-Chg-Ala-Arg-Dpr(4FB)-NH2	Agonist	7.89	pEC50
Isox-Cha-Chg-ARK(Sulfo-Cy5)-NH2	Agonist	7.8	pEC50
AZ3451	Negative	7.64	pIC50
AC264613	Agonist	7.5	pEC50
AY77	Agonist	7.48	pEC50
I-191	Antagonist	7.1	pIC50
AZ2429	Full agonist	6.7	pEC50
AC-55541	Agonist	6.7	pEC50
GB110	Agonist	6.55	pEC50
I-287	Negative	6.41	pIC50
GB88	Antagonist	5.7	pIC50
AZ8838	Antagonist	5.64	pIC50
2-furoyl-LIGRLO-amide	Full agonist	5.4	pKi
P2pal18S	Antagonist	5.4	pIC50
AZ7188	Antagonist	5.22	pIC50
AC-98170	Agonist	5.2	pEC50
C391	Antagonist	4.84	pIC50

Binding affinities (BindingDB)

54 measured of 60 human assays (60 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(R)-(3-ethyl-8-fluoroindolizin-5-yl)-(1H-imidazol-2-yl)methanol	IC50	200 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3-ethyl-8-fluoroindolizin-5-yl)-(1H-imidazol-2-yl)methanol	IC50	300 nM	US-10550089: Inhibitors of protease-activated receptor-2
(S)-(3-ethyl-7-fluoro-1-benzofuran-4-yl)-(1H-imidazol-2-yl)methanol	IC50	330 nM	US-10550089: Inhibitors of protease-activated receptor-2
(R)-(3-ethyl-7-fluoro-1-benzothiophen-4-yl)-(1H-imidazol-2-yl)methanol	IC50	600 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3-ethyl-7-fluoro-1-benzofuran-4-yl)-(1H-imidazol-2-yl)methanol	IC50	750 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3-cyclopropyl-7-fluoro-1-benzofuran-4-yl)-(1H-imidazol-2-yl)methanol	IC50	860 nM	US-10550089: Inhibitors of protease-activated receptor-2
(R)-[2-(2,5-dihydropyrrol-1-yl)-4-fluorophenyl]-(1H-imidazol-2-yl)methanol	IC50	900 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-8-methylnaphthalen-1-yl)-(1H-imidazol-2-yl)methanol	IC50	900 nM	US-10550089: Inhibitors of protease-activated receptor-2
(S)-(4-fluoro-2-pyrrolidin-1-ylphenyl)-(1H-imidazol-2-yl)methanol	IC50	960 nM	US-10550089: Inhibitors of protease-activated receptor-2
(8-fluoro-3-methylindolizin-5-yl)-(1H-imidazol-2-yl)methanol	IC50	970 nM	US-10550089: Inhibitors of protease-activated receptor-2
(S)-(3-ethyl-7-fluoro-1-benzothiophen-4-yl)-(1H-imidazol-2-yl)methanol	IC50	970 nM	US-10550089: Inhibitors of protease-activated receptor-2
[2-(2,5-dihydropyrrol-1-yl)-4-fluorophenyl]-(1H-imidazol-2-yl)methanol	IC50	1050 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-1-methylindazol-7-yl)-(1H-imidazol-2-yl)methanol	IC50	1230 nM	US-10550089: Inhibitors of protease-activated receptor-2
(R)-(4-fluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol	IC50	1290 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-1-methylindol-7-yl)-(1H-imidazol-2-yl)methanol	IC50	1390 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluorodibenzofuran-1-yl)-(1H-imidazol-2-yl)methanol	IC50	1450 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-2-pyrrolidin-1-ylphenyl)-(1H-imidazol-2-yl)methanol	IC50	1520 nM	US-10550089: Inhibitors of protease-activated receptor-2
(7-fluoro-3-methyl-1-benzofuran-4-yl)-(1H-imidazol-2-yl)methanol	IC50	1630 nM	US-10550089: Inhibitors of protease-activated receptor-2
(S)-(4-fluoro-1-methylindol-7-yl)-(1H-imidazol-2-yl)methanol	IC50	1650 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3,4-difluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol	IC50	1660 nM	US-10550089: Inhibitors of protease-activated receptor-2
(1-ethyl-5-fluoroindolizin-8-yl)-(1H-imidazol-2-yl)methanol	IC50	1900 nM	US-10550089: Inhibitors of protease-activated receptor-2
(8-fluoro-3-propan-2-ylindolizin-5-yl)-(1H-imidazol-2-yl)methanol	IC50	1910 nM	US-10550089: Inhibitors of protease-activated receptor-2
(R)-[7-fluoro-3-(2,2,2-trifluoroethyl)-1-benzofuran-4-yl]-(1H-imidazol-2-yl)methanol	IC50	2120 nM	US-10550089: Inhibitors of protease-activated receptor-2
[7-fluoro-3-(2,2,2-trifluoroethyl)-1-benzofuran-4-yl]-(1H-imidazol-2-yl)methanol	IC50	2170 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol	IC50	2930 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3-chloro-8-fluoroindolizin-5-yl)-(1H-imidazol-2-yl)methanol	IC50	3380 nM	US-10550089: Inhibitors of protease-activated receptor-2
[4-fluoro-2-(1,3-thiazol-4-yl)phenyl]-(1H-imidazol-2-yl)methanol	IC50	3600 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-Fluoro-2-((S)-3- fluoropyrrolidin-1- yl)phenyl)(1H-imidazol- 2-yl)methanol	IC50	3870 nM	US-10550089: Inhibitors of protease-activated receptor-2
(S)-(3,4-difluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol	IC50	4000 nM	US-10550089: Inhibitors of protease-activated receptor-2
[2-(1-bicyclo[3.1.0]hexanyl)-4-fluorophenyl]-(1H-imidazol-2-yl)methanol	IC50	4320 nM	US-10550089: Inhibitors of protease-activated receptor-2
[2-(azetidin-1-yl)-4-fluorophenyl]-(1H-imidazol-2-yl)methanol	IC50	4500 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3,4-difluoro-2-pyrazol-1-ylphenyl)-(1H-imidazol-2-yl)methanol	IC50	4600 nM	US-10550089: Inhibitors of protease-activated receptor-2
(2-(3- Azabicyclo[3.1.0] hexan-3-yl)-4- fluorophenyl)(1H- imidazol-2-yl)methanol	IC50	4670 nM	US-10550089: Inhibitors of protease-activated receptor-2
(2-(3,3- Difluoropyrrolidin-1- yl)-4-fluorophenyl)(1H- imidazol-2-yl)methanol	IC50	4910 nM	US-10550089: Inhibitors of protease-activated receptor-2
(2-cyclopentyl-4-fluorophenyl)-(1H-imidazol-2-yl)methanol	IC50	5000 nM	US-10550089: Inhibitors of protease-activated receptor-2
[2-(cyclopenten-1-yl)-4-fluorophenyl]-(1H-imidazol-2-yl)methanol	IC50	5180 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3-chloro-2-propylphenyl)-(1H-imidazol-2-yl)methanol	IC50	5450 nM	US-10550089: Inhibitors of protease-activated receptor-2
[4-fluoro-2-[(E)-prop-1-enyl]phenyl]-(1H-imidazol-2-yl)methanol	IC50	5640 nM	US-10550089: Inhibitors of protease-activated receptor-2
[2-(cyclopenten-1-yl)phenyl]-(1H-imidazol-2-yl)methanol	IC50	6270 nM	US-10550089: Inhibitors of protease-activated receptor-2
(3-chloro-2-pyrazol-1-ylphenyl)-(1H-imidazol-2-yl)methanol	IC50	6400 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-Fluoro-2-(3-fluoro-3- methylazetidin-1- yl)phenyl)(1H-imidazol- 2-yl)methanol	IC50	6730 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-Fluoro-2-(3- methylazetidin-1- yl)phenyl)(1H-imidazol- 2-yl)methanol	IC50	6880 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-Fluoro-2-((R)-3- fluoropyrrolidin-1- yl)phenyl)(1H-imidazol- 2-yl)methanol	IC50	6960 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-2-pyrazol-1-ylphenyl)-(1H-imidazol-2-yl)methanol	IC50	7210 nM	US-10550089: Inhibitors of protease-activated receptor-2
(1-ethyl-4-fluoroindol-7-yl)-(1H-imidazol-2-yl)methanol	IC50	7210 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-fluoro-2-pyrrolidin-1-ylphenyl)-(1H-1,2,4-triazol-5-yl)methanol	IC50	7790 nM	US-10550089: Inhibitors of protease-activated receptor-2
(5-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-8-yl)-(1H-imidazol-2-yl)methanol	IC50	9230 nM	US-10550089: Inhibitors of protease-activated receptor-2
[4-fluoro-2-[(Z)-prop-1-enyl]phenyl]-(1H-imidazol-2-yl)methanol	IC50	9660 nM	US-10550089: Inhibitors of protease-activated receptor-2
(2-cyclobutyl-4-fluorophenyl)-(1H-imidazol-2-yl)methanol	IC50	11500 nM	US-10550089: Inhibitors of protease-activated receptor-2
(4-Fluoro-2-((R)-3- methylpyrrolidin-1- yl)phenyl)(1H-imidazol- 2-yl)methanol	IC50	13100 nM	US-10550089: Inhibitors of protease-activated receptor-2

ChEMBL bioactivities

409 potent at pChembl≥5 of 479 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.15	IC50	0.7	nM	CHEMBL5273903
8.70	IC50	2	nM	CHEMBL3582250
8.70	IC50	2	nM	CHEMBL3582248
8.70	IC50	2	nM	CHEMBL4470628
8.40	EC50	4	nM	CHEMBL2431724
8.38	IC50	4.2	nM	CHEMBL3582251
8.32	IC50	4.8	nM	CHEMBL3582251
8.30	IC50	5	nM	CHEMBL3582250
8.30	IC50	5	nM	CHEMBL3582248
8.00	EC50	10	nM	CHEMBL2431724
7.85	IC50	14	nM	TRIPTOLIDE
7.75	EC50	18	nM	CHEMBL4100763
7.70	EC50	19.95	nM	CHEMBL4100763
7.64	IC50	23	nM	TRIPTOLIDE
7.64	IC50	23	nM	CHEMBL5431335
7.64	IC50	23	nM	CHEMBL4128763
7.60	EC50	25	nM	CHEMBL2431720
7.60	EC50	25.12	nM	CHEMBL459723
7.60	EC50	25.12	nM	CHEMBL509819
7.52	EC50	30	nM	CHEMBL494502
7.50	EC50	31.62	nM	CHEMBL4095478
7.50	EC50	31.62	nM	CHEMBL494502
7.48	EC50	33	nM	CHEMBL4095478
7.30	EC50	50.12	nM	CHEMBL461639
7.21	EC50	62	nM	CHEMBL4073996
7.21	EC50	62	nM	CHEMBL4798456
7.20	EC50	63.1	nM	CHEMBL4073996
7.14	EC50	73	nM	CHEMBL4782345
7.10	EC50	79.43	nM	CHEMBL4092076
7.10	EC50	79.43	nM	CHEMBL4093061
7.10	EC50	80	nM	CHEMBL4092076
7.10	EC50	80	nM	CHEMBL4093061
7.08	EC50	84	nM	CHEMBL4793975
7.05	EC50	90	nM	CHEMBL4793975
7.05	IC50	90	nM	CHEMBL5404935
7.02	EC50	95	nM	CHEMBL4071278
7.00	EC50	100	nM	CHEMBL238396
7.00	EC50	100	nM	CHEMBL267729
7.00	EC50	100	nM	CHEMBL414319
7.00	EC50	100	nM	CHEMBL236037
7.00	EC50	100	nM	CHEMBL236292
7.00	EC50	100	nM	CHEMBL236293
7.00	EC50	100	nM	CHEMBL398128
7.00	EC50	100	nM	CHEMBL392253
7.00	IC50	100	nM	CHEMBL509819
7.00	IC50	100	nM	CHEMBL2431716
7.00	EC50	100	nM	CHEMBL4071278
7.00	IC50	100	nM	CHEMBL4470628
6.96	IC50	109	nM	CHEMBL2431716
6.90	EC50	125.9	nM	CHEMBL459509

PubChem BioAssay actives

252 with measured affinity, of 714 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
(2R)-1-[(2S)-4-[6-(4-fluorophenyl)-8-propan-2-ylimidazo[1,2-b]pyridazine-2-carbonyl]-2-methylpiperazin-1-yl]-2-hydroxy-4,4-dimethylpentan-1-one	1934086: Inhibition of PAR2 expressed in human HT-29 cells incubated for 30 mins by FLIPR Tetra system method	ic50	0.0007	uM
tert-butyl 4-[6-(4-fluorophenyl)-8-propan-2-ylimidazo[1,2-b]pyridazine-2-carbonyl]-3,3-dimethylpiperazine-1-carboxylate	1229060: Antagonist activity against PAR2 in human HT29 cells assessed as inhibition of SLIGKV-induced Ca2+ responses pre-incubated for 30 mins before SLIGKV stimulation by FLIPR assay	ic50	0.0020	uM
1-[(2S)-4-[6-(4-fluorophenyl)-8-propan-2-ylimidazo[1,2-b]pyridazine-2-carbonyl]-2-methylpiperazin-1-yl]-2-thiophen-3-ylethanone	1229060: Antagonist activity against PAR2 in human HT29 cells assessed as inhibition of SLIGKV-induced Ca2+ responses pre-incubated for 30 mins before SLIGKV stimulation by FLIPR assay	ic50	0.0020	uM
4-[4-[6-(4-fluorophenyl)-8-propan-2-ylimidazo[1,2-b]pyridazine-2-carbonyl]-3,3-dimethylpiperazin-1-yl]-4-oxobutanoic acid	1515634: Antagonist activity at PAR2 in human EAhy926 cells assessed as inhibition of trypsin-induced intracellular calcium mobilization preincubated for 15 mins followed by trypsin addition by Fluo-4-AM dye based fluorescence assay	ic50	0.0020	uM
2-(6-bromo-1,3-benzodioxol-5-yl)-N-(4-cyanophenyl)-1-[(1S)-1-cyclohexylethyl]benzimidazole-5-carboxamide	1512739: Antagonist activity at human PAR2	ic50	0.0025	uM
2-[2-[2-[[(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[(2-amino-1,3-thiazole-4-carbonyl)amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentyl]amino]ethoxy]ethoxy]ethyl hexadecanoate	772491: Agonist activity at PAR2 in human 16HBE14o- cells assessed as increase in intracellular calcium level	ec50	0.0040	uM
tert-butyl 4-[8-tert-butyl-6-(4-fluorophenyl)imidazo[1,2-b]pyridazine-2-carbonyl]-3,3-dimethylpiperazine-1-carboxylate	1229060: Antagonist activity against PAR2 in human HT29 cells assessed as inhibition of SLIGKV-induced Ca2+ responses pre-incubated for 30 mins before SLIGKV stimulation by FLIPR assay	ic50	0.0042	uM
(1S,2S,4S,5S,7R,8R,9S,11S,13S)-8-hydroxy-1-methyl-7-propan-2-yl-3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-en-17-one	772483: Antagonist activity at human PAR2 expressed in human A549 cells assessed as inhibition of 2f-LIGRLO-NH2-induced NFkappaB activation by luciferase reporter gene assay	ic50	0.0140	uM
N-[1-[[2-[(2-amino-2-oxoethyl)amino]-1-cyclohexyl-2-oxoethyl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.0180	uM
2-(6-bromo-1,3-benzodioxol-5-yl)-N-(4-cyanophenyl)-1-(1-cyclohexylethyl)benzimidazole-5-carboxamide	1973688: Antagonist activity at PAR2 (unknown origin) expressed in human 1321N1 cells	ic50	0.0230	uM
(4S)-5-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-(hexadecanoylamino)pentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-carboxypropanoyl]amino]-5-oxopentanoic acid	772473: Agonist activity at human PAR2 expressed in African green monkey COS7 cells assessed as stimulation of inositol triphosphate production	ec50	0.0250	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1-[[(2S)-1,5-diamino-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]furan-2-carboxamide	363236: Agonist activity at human PAR2 expressed in HEK293T cells assessed as effect on intracellular calcium mobilization by R-SAT assay	ec50	0.0251	uM
(3S,4R)-4-(3-bromophenyl)-N-[(E)-1-(3-bromophenyl)ethylideneamino]-2-oxopyrrolidine-3-carboxamide	363236: Agonist activity at human PAR2 expressed in HEK293T cells assessed as effect on intracellular calcium mobilization by R-SAT assay	ec50	0.0251	uM
(3S,4R)-N-[(E)-1-(3-bromophenyl)ethylideneamino]-2-oxo-4-phenylpyrrolidine-3-carboxamide	772487: Agonist activity at human PAR2 expressed in HEK293T cells assessed as increase in intracellular calcium level by bioluminescence assay	ec50	0.0300	uM
N-[(2S)-1-[[(1S)-2-amino-1-cyclohexyl-2-oxoethyl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.0316	uM
(3S,4R)-N-[(E)-1-(3-bromophenyl)ethylideneamino]-1-(2-methylprop-1-enyl)-2-oxo-4-phenylpyrrolidine-3-carboxamide	363236: Agonist activity at human PAR2 expressed in HEK293T cells assessed as effect on intracellular calcium mobilization by R-SAT assay	ec50	0.0501	uM
N-[1-[[2-[[2-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-cyclohexyl-2-oxoethyl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.0620	uM
2-[(2S,5R,8S,11S)-8-[[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-[[(2S,3S)-2-[[(2S)-2-(furan-2-carbonylamino)-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methyl]-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,12,15-tetraoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;tris(2,2,2-trifluoroacetic acid)	1695460: Agonist activity at PAR2 in human EA.hy926 cells assessed as stimulation of calcium mobilization by Fluo-4-AM dye-based FLIPR assay	ec50	0.0620	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[2-[2-[2-[2-[2-[2-[2-[4-(methoxymethyl)triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]furan-2-carboxamide;bis(2,2,2-trifluoroacetic acid)	1695460: Agonist activity at PAR2 in human EA.hy926 cells assessed as stimulation of calcium mobilization by Fluo-4-AM dye-based FLIPR assay	ec50	0.0730	uM
N-[1-[[2-[[2-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-cyclohexyl-2-oxoethyl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.0794	uM
N-[1-[[(2S,3S)-1-[[2-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.0794	uM
2-[(2S,5R,8S,11S)-5-benzyl-8-[[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[(2S)-2-cyclohexyl-2-[[(2S)-3-cyclohexyl-2-(1,2-oxazole-5-carbonylamino)propanoyl]amino]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methyl]-11-[3-(diaminomethylideneamino)propyl]-3,6,12,15-tetraoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;tris(2,2,2-trifluoroacetic acid)	1695460: Agonist activity at PAR2 in human EA.hy926 cells assessed as stimulation of calcium mobilization by Fluo-4-AM dye-based FLIPR assay	ec50	0.0840	uM
2-(6-bromo-1,3-benzodioxol-5-yl)-N-phenyl-1-[(1S)-1-phenylethyl]benzimidazole-5-carboxamide	2034413: Antagonist activity at PAR2 (unknown origin)	ic50	0.0900	uM
N-[1-[[(2S,3S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.0950	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]naphthalene-2-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzothiophene-2-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyridine-2-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyridine-3-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrazine-2-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-1,2-oxazole-5-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-2-methyl-1,3-oxazole-4-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.1000	uM
N-[(2S)-3-cyclohexyl-1-[[(2S,3S)-3-methyl-1-oxo-1-(4-phenylpiperidin-1-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1327851: Agonist activity at human PAR2 expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 20 mins followed by forskolin addition for 10 mins measured after 1 hr by LANCE assay	ic50	0.1000	uM
(3S,4R)-N-[(E)-(6-bromo-2,3-dihydroinden-1-ylidene)amino]-2-oxo-4-phenylpyrrolidine-3-carboxamide	363236: Agonist activity at human PAR2 expressed in HEK293T cells assessed as effect on intracellular calcium mobilization by R-SAT assay	ec50	0.1259	uM
2-[(2S,5R,8S,11S)-8-[[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-[[(2S,3S)-2-[[(2S)-2-(furan-2-carbonylamino)-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]pentanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methyl]-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,12,15-tetraoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;tris(2,2,2-trifluoroacetic acid)	1695460: Agonist activity at PAR2 in human EA.hy926 cells assessed as stimulation of calcium mobilization by Fluo-4-AM dye-based FLIPR assay	ec50	0.1300	uM
prop-2-enyl N-[(4S)-5-amino-4-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-[[(2S,3S)-2-[[(2S)-2-(furan-2-carbonylamino)-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentyl]carbamate	587681: Agonist activity at PAR2 in human 16HBE14o cells assessed as increase in intracellular calcium levels measured every 15 second for 2 hrs by xCelligence real time cell analyzer	ec50	0.1380	uM
(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-(hexadecanoylamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]hexanoic acid	772467: Antagonist activity at PAR2 in human neutrophils assessed as inhibition of chemotactic migration of cells towards trypsin/SLIGRL-NH2	ic50	0.1400	uM
2-amino-N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-1,3-thiazole-4-carboxamide	587681: Agonist activity at PAR2 in human 16HBE14o cells assessed as increase in intracellular calcium levels measured every 15 second for 2 hrs by xCelligence real time cell analyzer	ec50	0.1420	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]furan-2-carboxamide	301247: Agonist activity at PAR2 expressed in human HT29 cells assessed as intracellular calcium release	ec50	0.1600	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-(4-nitrophenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]furan-2-carboxamide	301247: Agonist activity at PAR2 expressed in human HT29 cells assessed as intracellular calcium release	ec50	0.1700	uM
N-[1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.1995	uM
N-[(2S)-1-[[(2S,3S)-1-[[3-[4-(aminomethyl)piperidine-1-carbonyl]phenyl]methylamino]-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	1433198: Agonist activity at human PAR2 expressed in CHO cells assessed as induction of intracellular calcium release measured for 300 secs by Fluo-3 AM dye-based fluorescence assay	ec50	0.1995	uM
N-[2-[(2E)-2-[1-(3-bromophenyl)ethylidene]hydrazinyl]-2-oxo-1-(4-oxo-3H-phthalazin-1-yl)ethyl]benzamide	363236: Agonist activity at human PAR2 expressed in HEK293T cells assessed as effect on intracellular calcium mobilization by R-SAT assay	ec50	0.1995	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-3-(4-nitrophenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]furan-2-carboxamide	301247: Agonist activity at PAR2 expressed in human HT29 cells assessed as intracellular calcium release	ec50	0.2000	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-3-(4-nitrophenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]furan-2-carboxamide	772493: Agonist activity at PAR2 in human HT-29 cells assessed as increase in intracellular calcium release	ec50	0.2000	uM
(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(3,4-dichlorophenyl)propanoyl]amino]-3-methylpentanamide	301247: Agonist activity at PAR2 expressed in human HT29 cells assessed as intracellular calcium release	ec50	0.3000	uM
(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1-benzothiophen-3-yl)propanoyl]amino]-3-methylpentanamide	301247: Agonist activity at PAR2 expressed in human HT29 cells assessed as intracellular calcium release	ec50	0.3000	uM
6-amino-N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyridine-3-carboxamide	587681: Agonist activity at PAR2 in human 16HBE14o cells assessed as increase in intracellular calcium levels measured every 15 second for 2 hrs by xCelligence real time cell analyzer	ec50	0.3110	uM
N-[(2S)-1-[[(2S,3S)-1-[4-[2-[4-(aminomethyl)piperidin-1-yl]-2-oxoethyl]anilino]-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide	526378: Agonist activity at PAR2 receptor in human HT-29 cells assessed as induction of intracellular calcium release	ec50	0.3162	uM
N-[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-(4-iodophenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-2-methyl-1,3-oxazole-4-carboxamide	301247: Agonist activity at PAR2 expressed in human HT29 cells assessed as intracellular calcium release	ec50	0.3200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	8
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	4
Estradiol	affects cotreatment, increases expression, decreases expression, decreases reaction	4
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression	3
Cyclosporine	increases expression, decreases expression	3
Particulate Matter	increases reaction, affects cotreatment, increases abundance, increases expression	3
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
entinostat	increases expression, affects cotreatment	2
belinostat	decreases expression, increases expression, affects cotreatment	2
Arsenic Trioxide	increases expression, decreases response to substance	2
Panobinostat	affects cotreatment, increases expression	2
Vehicle Emissions	increases expression, increases reaction, decreases reaction, increases secretion	2
Barium	increases transport, affects reaction, decreases reaction	2
Methotrexate	increases expression	2
Smoke	decreases expression	2
cyclopiazonic acid	decreases reaction, increases transport	1
sotorasib	affects cotreatment, decreases expression	1
allyl isothiocyanate	decreases reaction, increases activity, increases reaction	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression, increases expression	1
quercitrin	increases expression	1
cinnamaldehyde	decreases reaction, increases activity, increases reaction	1
tris(2-butoxyethyl) phosphate	affects expression	1
dodecyldimethylamine oxide	increases expression	1
methylparaben	decreases expression	1
tanshinone	increases expression	1

ChEMBL screening assays

146 unique, capped per target: 92 functional, 50 binding, 3 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001577	Functional	Antagonist activity at human recombinant PAR2 expressed in A549 cells assessed as inhibition of SLIGKV-NH2-induced intracellular calcium mobilization	Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists. — J Med Chem
CHEMBL1262315	Binding	Inhibition of PAR2-mediated IL1-beta and SLIGKV-NH2-induced interleukin-8 production in normal human epidermal keratinocytes at 10 uM by ELISA	Effect of 14-membered-ring macrolides on production of interleukin-8 mediated by protease-activated receptor 2 in human keratinocytes. — Antimicrob Agents Chemother
CHEMBL4619233	ADMET	Agonist activity at PK1-tagged PAR2 (unknown origin) expressed in HEK293 cells assessed as induction of beta-arrestin recruitment incubated for 90 mins by Pathhunter chemiluminescent assay	Discovery of Novel Nonpeptidic PAR2 Ligands. — ACS Med Chem Lett

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D2AP	Abcam HCT 116 F2RL1 KO	Cancer cell line	Male
CVCL_D7GE	Ubigene HEK293T F2RL1 KO	Transformed cell line	Female
CVCL_H493	CHO-K1/PAR2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU55	CHO-K1 F2RL1 Gq	Spontaneously immortalized cell line	Female
CVCL_KZ47	PathHunter HEK 293 F2RL1 beta-arrestin	Transformed cell line	Female
CVCL_LA27	PathHunter U2OS F2RL1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_LA28	PathHunter U2OS F2RL1 beta-arrestin	Cancer cell line	Female
CVCL_SM71	HAP1 F2RL1 (-) 1	Cancer cell line	Male
CVCL_XN62	HAP1 F2RL1 (-) 2	Cancer cell line	Male
CVCL_ZL09	Tango F2RL1-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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