PTGFR

Summary

PTGFR (prostaglandin F receptor, HGNC:9600) is a protein-coding gene on chromosome 1p31.1, encoding Prostaglandin F2-alpha receptor (P43088). Receptor for prostaglandin F2-alpha (PGF2-alpha).

The protein encoded by this gene is member of the G-protein coupled receptor family. This protein is a receptor for prostaglandin F2-alpha (PGF2-alpha), which is known to be a potent luteolytic agent, and may also be involved in modulating intraocular pressure and smooth muscle contraction in uterus. Knockout studies in mice suggest that the interaction of PGF2-alpha with this receptor may initiate parturition in ovarian luteal cells and thus induce luteolysis. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5737 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 48 total
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9600
Approved symbol	PTGFR
Name	prostaglandin F receptor
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	FP
Ensembl gene	ENSG00000122420
Ensembl biotype	protein_coding
OMIM	600563
Entrez	5737

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000370756, ENST00000370757, ENST00000370758, ENST00000497923, ENST00000885093, ENST00000885094, ENST00000885095, ENST00000945159

RefSeq mRNA: 2 — MANE Select: NM_000959 NM_000959, NM_001039585

CCDS: CCDS30759, CCDS686

Canonical transcript exons

ENST00000370757 — 3 exons

Exon	Start	End
ENSE00002177701	78492672	78493541
ENSE00003841492	78536406	78540701
ENSE00003848876	78490974	78491236

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 95.16.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4661 / max 535.8679, expressed in 723 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3664	6.0842	710
3666	0.2220	59
3667	0.0812	21
3668	0.0406	15
3663	0.0263	8
3665	0.0118	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.16	gold quality
mucosa of stomach	UBERON:0001199	88.33	gold quality
tibial nerve	UBERON:0001323	87.34	gold quality
bronchial epithelial cell	CL:0002328	85.86	gold quality
synovial joint	UBERON:0002217	83.39	gold quality
epithelium of bronchus	UBERON:0002031	82.70	gold quality
smooth muscle tissue	UBERON:0001135	81.52	gold quality
bronchus	UBERON:0002185	81.44	gold quality
stromal cell of endometrium	CL:0002255	81.28	gold quality
tendon	UBERON:0000043	81.02	gold quality
urethra	UBERON:0000057	80.33	gold quality
skin of hip	UBERON:0001554	80.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.14	gold quality
gall bladder	UBERON:0002110	78.92	gold quality
right coronary artery	UBERON:0001625	78.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.36	gold quality
body of uterus	UBERON:0009853	77.77	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.67	gold quality
tibial artery	UBERON:0007610	77.33	gold quality
popliteal artery	UBERON:0002250	77.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.74	gold quality
nipple	UBERON:0002030	75.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.17	gold quality
skin of leg	UBERON:0001511	74.84	gold quality
pericardium	UBERON:0002407	74.50	gold quality
zone of skin	UBERON:0000014	73.90	gold quality
left coronary artery	UBERON:0001626	73.86	gold quality
left uterine tube	UBERON:0001303	73.55	gold quality
skin of abdomen	UBERON:0001416	73.35	gold quality
minor salivary gland	UBERON:0001830	72.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, GATA1, NFKB1, NFKB, NKX3-1, RELA, SP1, STAT1, USF1

miRNA regulators (miRDB)

153 targeting PTGFR, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-450A-1-3P	100.00	69.33	1837
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-5692A	100.00	74.40	6850
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Literature-anchored findings (GeneRIF, showing 40)

• identification of amino acids contributing to ligand speificity or signal transduction properties of this protein (PMID:12519077)
• isolation and sequencing of 4106-bp promoter DNA fragment that contains -2436-bp of 5’-flanking sequence; identification of transcription initiation start site (PMID:14746914)
• PGF(2 alpha)-FP receptor may promote endometrial tumorigenesis via phospholipase C-mediated phosphorylation of EGF receptor and MAPK signaling pathways. (PMID:14764825)
• prostaglandin F2alpha production is stimulated by withdrawal of ovarian steroids through nuclear factor-kappaB activation via oxygen radicals (PMID:15118249)
• Alterations in the amino acid sequence of the C-terminal domain of PTGFR and their effects on GTP-binding protein signalling are reported. (PMID:15651980)
• The regulation of the FP receptor and the stimulation of production of PGF2alpha in melanocytes in response to ultraviolet radiation suggest that PGF2alpha could act as an autocrine factor for melanocyte differentiation. (PMID:15748887)
• uteroglobin plays important roles in maintaining homeostasis in organs that are vulnerable to inadvertent stimulation of FP-mediated inflammatory response by inhibiting the prostaglandin F2alpha receptor (PMID:16061484)
• The rabbit prostaglandin F receptor (FP) couples to the inhibitory G protein, Gi, to inhibit vasopressin action in the cortical collecting duct. (PMID:16096282)
• FP receptor activation of Rho signaling by PGF(2alpha) can interfere with nuclear division (PMID:16378246)
• NFkappaB is involved in both basal and interleukin 1beta-stimulated transcription of the PTGFR gene. (PMID:16855208)
• level at term may facilitate the decidua contribution to parturition, and its regulation and role should be examined further. (PMID:16911823)
• rs3753380 and rs3766355, SNPs in the promoter and intron 1 regions of the FP receptor gene, correlate with a response to short-term latanoprost treatment in normal volunteers. (PMID:17467803)
• role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line (PMID:17478553)
• A novel PGF2alpha receptor single nucleotide polymorphism (SNP), IVS -97A>T, is common in the Malaysian patients with glaucoma. (PMID:17582204)
• Data show that prostag;andins E2 and F2alpha can mobilize inositol 1,4,5-trisphosphate, induce ERK1/2 phosphorylation and induce cyclooxygenase-2 expression via the FP receptor. (PMID:18316157)
• Bimatoprost lacks effects on the FP receptor but may interact with the FP-altFP receptor heterodimer to induce alterations in second messenger signalling. (PMID:18587449)
• FPR signalling mechanism(s) regulating MLC-2 phosphorylation likely extend beyond those classically established for G(q/11)-coupled receptors (PMID:18703533)
• urinary 8-iso-prostaglandin excretion is enhanced in microalbuminuric compared to nonmicroalbuminuric hypertensive patients or controls (PMID:19280705)
• Expression and functional evidence of the PTGFR mediating contraction in human umbilical vein are reported. (PMID:19289115)
• Oxytocin, its receptor and the PGF(2alpha) receptor are involved in the regulation of labour through a paracrine mechanism. (PMID:19347709)
• demonstrates that co-activation of the FP and EP2 receptors results in enhanced release of cAMP via FP receptor-G alpha(q)-Ca(2+)-calmodulin pathway by activating calcium sensitive adenylyl cyclase 3 isoform. (PMID:19782748)
• our data have elucidated the molecular and cellular mechanism whereby PGF(2alpha) regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression (PMID:19819266)
• This study investigated the expression of IL-11 and role of prostaglandin F(2alpha)-F-prostanoid receptor (FP receptor) signaling in the modulation of IL-11 expression in endometrial adenocarcinoma cells. (PMID:20008143)
• The prostaglandin F(2alpha) can directly regulate endothelial cell network formation but not endothelial cell proliferation. (PMID:20092633)
• Data show a labour-associated decrease in PTGFR-v1 and PTGFR transcript variant 2 mRNA expression in lower segment myometrial samples. (PMID:20519365)
• Dental pulp cells expressed prostaglandin FP receptors as analysed by RT-PCR, which showed the presence of 396-bp PCR product. Pulp cells also expressed FP receptor protein (64 kD) as analysed by Western blotting. (PMID:20536573)
• These data demonstrate a role for the FP receptor in regulation of the chemokine CCL20, which can mediate proliferation of endometrial adenocarcinoma epithelial cells. (PMID:20816914)
• we found no indication for an association between SNPs in the prostaglandin F(2alpha) receptor gene or SLCO2A1 and IOP response to prostaglandin analogs in a population of European descent. (PMID:22060278)
• The results of this study suggested that significant novel association signals near the genes PTGFR, and provide supportive evidence for the previously reported association signals near ANK3 and within the 3p21.1 locus. (PMID:22182935)
• we provide evidence that PGF2alpha induces COX-2 expression via the FP receptor and phosphorylates CREB1 by PKC, thus increasing CREB1 binding to the COX-2 promoter and the expression of COX-2 in human amnion fibroblasts. (PMID:22919060)
• The F-prostaglandin receptor is a novel marker for tumor endothelial cells in renal cell carcinoma. (PMID:23356224)
• An association was found between SNPs of the FP receptor gene and the response to latanoprost in patients with glaucoma or OH. (PMID:24457363)
• Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients (PMID:25339146)
• Angiotensin II type I and prostaglandin F2alpha receptors cooperatively modulate signaling in vascular smooth muscle cells (PMID:25512374)
• The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. (PMID:25704319)
• The results indicated that the rs12731181 G allele of the Prostaglandin F2alpha Receptor Gene was associated with susceptibility to essential hypertension. (PMID:25977569)
• these results indicated that the actions of AKR1C3 can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer. (PMID:26170067)
• The genotype frequencies of six SNPs in AFAP1, GMDS and PTGFR genes were conformed to Hardy-Weinberg equilibrium (HWE). (PMID:27862086)
• Data suggest that allosteric communication between heterodimeric AT1R and PTGFR is mediated through GNAQ and may also involve proximal phospholipase C but not distal protein kinase C signaling partners; PTGFR activation has negligible effects on AT1R-based conformational biosensors. (AT1R = angiotensin II receptor, type 1; PTGFR = prostaglandin F2alpha receptor; GNAQ = GTP-binding protein G[q] subunit alpha) (PMID:28584054)
• Data, including data from studies using transgenic mice, suggest that signaling via prostaglandin-F2alpha/PTGFR and Camk2g/p38/Foxo1 MAP kinase/calcium pathways are involved in regulation of hepatic gluconeogenesis in both obesity and fasting. (PTGFR = prostaglandin F2alpha receptor; Camk2g = calcium-calmodulin-dependent protein kinase type 2 gamma; p38 = p38 MAP kinase; Foxo1 = forkhead box transcription factor O1) (PMID:29773555)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptgfr	ENSDARG00000074016
mus_musculus	Ptgfr	ENSMUSG00000028036
rattus_norvegicus	Ptgfr	ENSRNOG00000046468
drosophila_melanogaster	CG7497	FBGN0036742

Paralogs (7): TBXA2R (ENSG00000006638), PTGER3 (ENSG00000050628), PTGER2 (ENSG00000125384), PTGIR (ENSG00000160013), PTGER1 (ENSG00000160951), PTGDR (ENSG00000168229), PTGER4 (ENSG00000171522)

Protein

Protein identifiers

Prostaglandin F2-alpha receptor — P43088 (reviewed: P43088)

Alternative names: Prostanoid FP receptor

All UniProt accessions (2): P43088, F2Z2Z6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum. Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and isoform 5 are proposed to be a receptor for prostamides including the synthetic analog bimatoprost.

Subunit / interactions. Isoform 1 can form heterodimers with isoform 5 (and probably other isoforms).

Subcellular location. Cell membrane.

Tissue specificity. Eye.

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

Isoforms (7)

UniProt ID	Names	Canonical?
P43088-1	1	yes
P43088-2	2, FP(S), VAR-1
P43088-3	3, VAR-2
P43088-4	4, VAR-3
P43088-5	5, altFP4, VAR-4
P43088-6	6, VAR-5
P43088-7	7, VAR-6

RefSeq proteins (2): NP_000950, NP_001034674 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000141	PglndnF_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR008365	Prostanoid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (50 total): helix 13, splice variant 11, topological domain 8, transmembrane region 7, turn 5, glycosylation site 2, strand 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8XJK	ELECTRON MICROSCOPY	2.63
8IUK	ELECTRON MICROSCOPY	2.67
8IQ4	ELECTRON MICROSCOPY	2.7
8XJL	ELECTRON MICROSCOPY	2.77
8IUL	ELECTRON MICROSCOPY	2.78
8XJM	ELECTRON MICROSCOPY	2.85
8IUM	ELECTRON MICROSCOPY	3.14
8IQ6	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43088-F1	80.73	0.53

Antibody-complex structures (SAbDab): 8 — 8IQ4, 8IQ6, 8IUK, 8IUL, 8IUM, 8XJK, 8XJL, 8XJM

Functional residue map

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

Disulfide bonds (1): 108–186

Glycosylation sites (2): 4, 19

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-391908	Prostanoid ligand receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 190 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_INFLAMMATORY_RESPONSE, REACTOME_EICOSANOID_LIGAND_BINDING_RECEPTORS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, EVI1_05, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MARTINEZ_RB1_TARGETS_UP, MODULE_289, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_PROSTAGLANDIN, GOBP_RESPONSE_TO_KETONE

GO Biological Process (13): inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cytosolic calcium ion concentration (GO:0007204), parturition (GO:0007567), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), response to estradiol (GO:0032355), response to lipopolysaccharide (GO:0032496), negative regulation of apoptotic process (GO:0043066), cellular response to prostaglandin D stimulus (GO:0071799), signal transduction (GO:0007165), response to lipid (GO:0033993)

GO Molecular Function (2): prostaglandin F receptor activity (GO:0004958), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (4): extracellular region (GO:0005576), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Eicosanoid ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to lipid	2
response to oxygen-containing compound	2
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
regulation of biological quality	1
multi-organism reproductive process	1
multi-multicellular organism process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
response to molecule of bacterial origin	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cellular response to prostaglandin stimulus	1
response to prostaglandin D	1
cellular response to alcohol	1
cellular response to ketone	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to chemical	1
prostaglandin receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGFR	PTGFRN	Q9P2B2	841
PTGFR	AKR1C3	P42330	729
PTGFR	PTGES	O14684	713
PTGFR	OXTR	P30559	586
PTGFR	KRT19	P08727	582
PTGFR	PTGS2	P35354	570
PTGFR	CD9	P21926	548
PTGFR	SLCO2A1	Q92959	543
PTGFR	PECAM1	P16284	524
PTGFR	PTGER4	P35408	521
PTGFR	PTGER2	P43116	507
PTGFR	ELMOD2	Q8IZ81	494
PTGFR	CD81	P18582	491
PTGFR	AGTR1	P30556	487
PTGFR	ADGRL4	Q9HBW9	480

IntAct

11 interactions, top by confidence:

A	B	Type	Score
PTGFR	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	PTGFR	psi-mi:“MI:0915”(physical association)	0.400
PTGFR	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	PTGFR	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	PTGFR	psi-mi:“MI:0915”(physical association)	0.400
PTGFR	ATP12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): NDFIP2 (Affinity Capture-MS), MBOAT7 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), DNAJC5 (Affinity Capture-MS), ALG6 (Affinity Capture-MS), RHBDD3 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), AGTR1 (Affinity Capture-Western), PTGFR (Affinity Capture-Western), PTGFR (Reconstituted Complex), AGTR1 (PCA), AGTR1 (FRET)

ESM2 similar proteins: A5D7K8, O35932, O95136, O95977, P21731, P30557, P30987, P34972, P34978, P34979, P34980, P35375, P35408, P37289, P43088, P43114, P43115, P43116, P43117, P43118, P43119, P43252, P43253, P46069, P47752, P47901, P47936, P50131, P52592, P56486, P70263, P70597, P79393, Q13258, Q28691, Q28905, Q5R949, Q62053, Q62928, Q8MJ08

Diamond homologs: O02662, P21731, P30557, P30987, P34978, P34979, P34980, P34995, P35375, P37289, P43088, P43115, P43117, P43118, P43119, P43141, P43252, P43253, P46069, P46626, P50131, P56486, P70597, P79393, Q28524, Q28550, Q28905, Q804Q2, Q804X9, Q8R456, Q95125, Q95252, Q9BGL8, Q9QXZ9, Q9TST4, Q9UHM6, Q9XT57, Q9XT58, P32240, P35408

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PTGFR	“up-regulates activity”	GNAS	binding
PTGFR	“up-regulates activity”	GNAL	binding
PTGFR	“up-regulates activity”	GNAQ	binding
PTGFR	“up-regulates activity”	GNA14	binding
“prostaglandin F2alpha(1-)”	“up-regulates activity”	PTGFR	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2917 predictions. Top by Δscore:

Variant	Effect	Δscore
1:78398949:A:AG	acceptor_gain	1.0000
1:78398950:G:GG	acceptor_gain	1.0000
1:78399021:GCCAT:G	donor_gain	1.0000
1:78399026:G:GG	donor_gain	1.0000
1:78503912:T:G	acceptor_gain	1.0000
1:78514635:GACA:G	donor_gain	1.0000
1:78536400:TTCTA:T	acceptor_loss	1.0000
1:78536401:TCTA:T	acceptor_loss	1.0000
1:78536402:CTAGG:C	acceptor_loss	1.0000
1:78536403:TA:T	acceptor_loss	1.0000
1:78536405:G:T	acceptor_loss	1.0000
1:78382597:A:AG	acceptor_gain	0.9900
1:78382598:G:GG	acceptor_gain	0.9900
1:78398950:GC:G	acceptor_gain	0.9900
1:78398950:GCC:G	acceptor_gain	0.9900
1:78398950:GCCA:G	acceptor_gain	0.9900
1:78398950:GCCAA:G	acceptor_gain	0.9900
1:78442670:C:T	donor_gain	0.9900
1:78443383:A:G	donor_gain	0.9900
1:78473340:T:A	acceptor_gain	0.9900
1:78493332:G:GT	donor_gain	0.9900
1:78493332:G:T	donor_gain	0.9900
1:78503911:A:AG	acceptor_gain	0.9900
1:78503915:AT:A	acceptor_gain	0.9900
1:78503916:T:TA	acceptor_gain	0.9900
1:78514627:G:GG	donor_gain	0.9900
1:78532350:TC:T	donor_gain	0.9900
1:78536404:A:AG	acceptor_gain	0.9900
1:78536405:G:GG	acceptor_gain	0.9900
1:78303930:AG:A	donor_loss	0.9800

AlphaMissense

2356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:78536511:T:A	W302R	0.998
1:78536511:T:C	W302R	0.998
1:78492939:T:C	F66L	0.997
1:78492941:T:A	F66L	0.997
1:78492941:T:G	F66L	0.997
1:78493122:A:C	S127R	0.997
1:78493124:T:A	S127R	0.997
1:78493124:T:G	S127R	0.997
1:78493302:T:C	F187L	0.997
1:78493304:C:A	F187L	0.997
1:78493304:C:G	F187L	0.997
1:78493527:T:A	W262R	0.997
1:78493527:T:C	W262R	0.997
1:78492974:T:A	D77E	0.996
1:78492974:T:G	D77E	0.996
1:78493037:G:C	W98C	0.996
1:78493037:G:T	W98C	0.996
1:78493078:G:A	G112D	0.996
1:78493296:T:A	W185R	0.996
1:78493296:T:C	W185R	0.996
1:78492875:C:A	N44K	0.995
1:78492875:C:G	N44K	0.995
1:78492972:G:C	D77H	0.995
1:78492973:A:C	D77A	0.995
1:78493130:G:A	M129I	0.995
1:78493130:G:C	M129I	0.995
1:78493130:G:T	M129I	0.995
1:78493298:G:C	W185C	0.995
1:78493298:G:T	W185C	0.995
1:78493299:T:A	C186S	0.995

dbSNP variants (sampled 300 via entrez): RS1000012908 (1:78540292 G>T), RS1000016320 (1:78495615 A>T), RS1000017647 (1:78499835 C>G), RS1000079200 (1:78523060 A>G), RS1000125949 (1:78511204 G>C), RS1000285922 (1:78509081 G>A), RS1000433598 (1:78489786 A>G), RS1000444365 (1:78504739 T>A), RS1000506953 (1:78490867 G>T), RS1000556489 (1:78491779 G>A,C), RS1000597644 (1:78498553 A>G,T), RS1000657707 (1:78497310 A>C,G), RS1000732266 (1:78504968 A>G), RS1000768393 (1:78491108 C>G,T), RS1000792994 (1:78532324 G>C)

Disease associations

OMIM: gene MIM:600563 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001358_1	Bipolar disorder	8.000000e-09
GCST002307_9	Systolic blood pressure (alcohol consumption interaction)	8.000000e-07
GCST003418_1	Skin fluorescence in type 1 diabetes	2.000000e-09
GCST004748_69	Lung cancer	3.000000e-06
GCST004749_61	Lung cancer in ever smokers	7.000000e-06
GCST008660_1	Lung function in never smokers (high FEV1 vs average FEV1)	3.000000e-07
GCST011678_2	Depression in multiple sclerosis (post-diagnosis)	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0006335	systolic blood pressure
EFO:0004314	forced expiratory volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1987 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,597 (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
CHEMBL426559	LAROPIPRANT	4	541
CHEMBL548	DINOPROSTONE	4	14,939
CHEMBL815	DINOPROST	4	3,118
CHEMBL4297633	SEPETAPROST	3	100
CHEMBL1201379	FLUPROSTENOL	2	1,846
CHEMBL2220404	CLOPROSTENOL	2
CHEMBL3975522	EBOPIPRANT	2	53

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3753380	Efficacy	3	latanoprost	Open-angle glaucoma
rs3766355	Efficacy	3	latanoprost	Open-angle glaucoma

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3753380	PTGFR	3	1.75	1	latanoprost
rs3766355	PTGFR	3	1.75	1	latanoprost

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Prostanoid receptors

Most potent curated ligand interactions (27 total), top 25:

Ligand	Action	Affinity	Parameter
cloprostenol	Full agonist	9.3	pKi
tafluprost acid	Agonist	9.28	pEC50
13,14-dihydro-16-m-chlorophenoxy-w-tetranor-PGF1α	Full agonist	9.0	pIC50
[3H]PGF2α	Full agonist	9.0	pKd
bimatoprost (free acid form)	Full agonist	8.7	pIC50
fluprostenol	Full agonist	8.6	pKi
latanoprost (free acid form)	Full agonist	8.6	pKi
latanoprostene bunod	Agonist	8.6	pKi
PGF2α	Full agonist	8.5	pKi
AL12180	Agonist	7.9	pEC50
PGD2	Full agonist	7.7	pKi
BAY-6672	Antagonist	7.66	pIC50
3H-fluprostenol	Agonist	7.5	pKd
AS604872	Antagonist	7.5	pKi
enprostil	Full agonist	7.1	pKi
I-BOP	Full agonist	7.0	pKi
PGE2	Full agonist	6.9	pKi
sulprostone	Full agonist	6.7	pKi
AL-8810	Partial agonist	6.7	pEC50
U46619	Full agonist	6.6	pKi
carbacyclin	Full agonist	6.5	pKi
latanoprost (isopropyl ester)	Full agonist	6.3	pKi
MB-28767	Full agonist	6.3	pKi
iloprost	Full agonist	6.2	pKi
ONO-9054	Agonist	5.52	pIC50

Binding affinities (BindingDB)

152 measured of 172 human assays (174 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_5311503	KI	0.3 nM
NSC_3080928	KI	0.4 nM
[(3S)-3-(4-fluorophenyl)-3-[[(2S)-3-(4-phenylphenyl)sulfonyl-1,3-thiazolidine-2-carbonyl]amino]propyl] (2S)-2-amino-3-methylbutanoate	KI	1 nM	US-9447055: α-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof
CAS_41598-07-6	KI	1.7 nM
(2S)-N-[(1S)-1-(4-fluorophenyl)-3-hydroxypropyl]-3-(4-phenylphenyl)sulfonyl-1,3-thiazolidine-2-carboxamide	KI	6 nM	US-9447055: α-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof
3-Fluoro-4-{[(6-iodo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}benzoic acid	IC50	6 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(3-Chloro-6-iodo-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	9 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-[(trifluoromethyl)sulfanyl]benzoic acid	IC50	17 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-[(methoxymethyl)sulfanyl]benzoic acid	IC50	17 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-chloro-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	17 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	20 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-[(3-chloro-6-iodo-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	22 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3,5-difluorobenzoic acid	IC50	22 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-7-chloro-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	25 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-[(methoxymethyl)sulfonyl]benzoic acid	IC50	27 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-cyclopropyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	27 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-[(trifluoromethyl)sulfonyl]benzoic acid	IC50	31 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-[(6-iodo-3-methyl-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	33 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
5-[(3-cyclopropyl-6-iodo-2-phenylquinoline-4-carbonyl)amino]bicyclo[3.2.2]nonane-1-carboxylic acid	IC50	33 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-{[(6,7-Dichloro-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	33 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-({[6-Bromo-2-(3-fluorophenyl)-3-methylquinolin-4-yl]carbonyl}amino)-3-fluorobenzoic acid	IC50	33 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-({[6-Bromo-3-(fluoromethyl)-2-phenylquinolin-4-yl]carbonyl}amino)-3-fluorobenzoic acid	IC50	39 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
3-Bromo-4-{[(6-bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}benzoic acid	IC50	41 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
[(Z)-6-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E)-3-hydroxy-4-phenoxybut-1-enyl]cyclopentyl]hex-4-enyl]-methylphosphinic acid	IC50	42 nM	US-9675539: Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-(trifluoromethyl)benzoic acid	IC50	45 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
5-[(3-chloro-6-iodo-2-phenylquinoline-4-carbonyl)amino]bicyclo[3.2.2]nonane-1-carboxylic acid	IC50	48 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-{[(6-Bromo-5-chloro-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	49 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-[(6-bromo-3-cyclopropyl-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	51 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-[(3-cyclopropyl-6-iodo-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	51 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-[(6-bromo-3-chloro-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	52 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-({[6-Bromo-2-(4-fluorophenyl)-3-methylquinolin-4-yl]carbonyl}amino)-3-fluorobenzoic acid	IC50	52 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-iodobenzoic acid	IC50	53 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-(trifluoromethoxy)benzoic acid	IC50	57 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-[[6-bromo-2-(4-bromothiophen-2-yl)-3-methylquinoline-4-carbonyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	58 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-nitrobenzoic acid	IC50	60 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-chlorobenzoic acid	IC50	65 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	66 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylate	IC50	68 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
8-[(6-iodo-3-methyl-2-phenylquinoline-4-carbonyl)amino]tricyclo[3.1.1.12,4]octane-3-carboxylic acid	IC50	73 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-[(6-bromo-3-methylsulfanyl-2-phenylquinoline-4-carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylic acid	IC50	74 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
3-Fluoro-4-({[3-methyl-2-phenyl-6-(trimethylsilyl)quinolin-4-yl]carbonyl}amino)benzoic acid	IC50	78 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
6-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-5-fluoronicotinic acid	IC50	79 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-3,5-dioxobicyclo[2.2.2]octane-1-carboxylic acid	IC50	82 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-2-fluorobicyclo[2.2.2]octane-1-carboxylic acid	IC50	83 nM	US-10117864: Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-(methylsulfonyl)benzoic acid	IC50	86 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
3-Fluoro-4-({[3-methyl-2-phenyl-6-(trifluoromethyl)quinolin-4-yl]carbonyl}amino)benzoic acid	IC50	93 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-5-(ethylsulfonyl)-2-methoxybenzoic acid	IC50	97 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-fluoro-2-phenylquinolin-4-yl)carbonyl]amino}-3-fluorobenzoic acid	IC50	98 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
6-Bromo-N-(4-carbamoyl-2-fluorophenyl)-3-methyl-2-phenylquinoline-4-carboxamide	IC50	102 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
4-{[(6-Bromo-3-methyl-1-oxido-2-phenylquinolin-4-yl)carbonyl]amino}-3-[(trifluoromethyl)sulfanyl]benzoic acid	IC50	102 nM	US-10189788: Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents

ChEMBL bioactivities

598 potent at pChembl≥5 of 612 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.28	IC50	0.53	nM	CHEMBL4752237
9.10	IC50	0.79	nM	CHEMBL4749822
9.08	IC50	0.83	nM	CHEMBL4752237
9.02	IC50	0.96	nM	CHEMBL6015710
9.00	Ki	1	nM	EBOPIPRANT
9.00	IC50	1	nM	CLOPROSTENOL
9.00	IC50	1	nM	CHEMBL36041
8.96	IC50	1.1	nM	CHEMBL4749767
8.96	IC50	1.1	nM	CHEMBL6015710
8.92	IC50	1.2	nM	CHEMBL5742825
8.80	IC50	1.6	nM	CHEMBL5939339
8.77	IC50	1.7	nM	CHEMBL5757389
8.74	IC50	1.8	nM	CHEMBL5749117
8.70	IC50	2	nM	CLOPROSTENOL
8.70	IC50	2	nM	CHEMBL5923206
8.70	IC50	2	nM	CHEMBL334398
8.62	IC50	2.4	nM	CHEMBL4749767
8.60	IC50	2.5	nM	DINOPROST
8.59	IC50	2.6	nM	CHEMBL36041
8.57	EC50	2.7	nM	CHEMBL185484
8.57	IC50	2.7	nM	CHEMBL5860295
8.55	IC50	2.8	nM	CHEMBL5954173
8.55	IC50	2.8	nM	CHEMBL4749767
8.52	IC50	3	nM	CHEMBL173299
8.52	IC50	3	nM	DINOPROST
8.49	IC50	3.2	nM	CHEMBL4749767
8.46	IC50	3.5	nM	CHEMBL5967650
8.44	EC50	3.6	nM	FLUPROSTENOL
8.44	IC50	3.6	nM	CHEMBL5799592
8.44	IC50	3.6	nM	CHEMBL5910941
8.43	IC50	3.7	nM	CHEMBL6063553
8.43	IC50	3.7	nM	CHEMBL6050132
8.42	EC50	3.8	nM	CHEMBL3956817
8.41	IC50	3.9	nM	CHEMBL5773404
8.40	IC50	4	nM	CHEMBL4784864
8.39	EC50	4.1	nM	CHEMBL3982726
8.39	IC50	4.1	nM	CHEMBL5872494
8.38	IC50	4.2	nM	CHEMBL5774694
8.37	IC50	4.3	nM	CHEMBL4754421
8.37	IC50	4.3	nM	CHEMBL5828838
8.36	IC50	4.4	nM	CHEMBL6013901
8.33	IC50	4.7	nM	CHEMBL6042895
8.31	IC50	4.9	nM	CHEMBL4779694
8.30	IC50	5	nM	CHEMBL4784864
8.30	IC50	5	nM	CHEMBL5947684
8.28	IC50	5.2	nM	CHEMBL4750252
8.28	IC50	5.3	nM	CHEMBL4779694
8.28	IC50	5.3	nM	CHEMBL5753655
8.28	IC50	5.2	nM	CHEMBL4754421
8.27	IC50	5.4	nM	CHEMBL6054387

PubChem BioAssay actives

178 with measured affinity, of 413 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
5-[[6-bromo-2-(3-ethylpiperidin-1-yl)-3-methylquinoline-4-carbonyl]amino]-4-(2-chlorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0005	uM
5-[(6-bromo-3-methyl-2-piperidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chloro-3,6-difluorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0008	uM
6-bromo-N-[2-(2-methoxyphenyl)propyl]-3-methyl-2-phenylquinoline-4-carboxamide	1677105: Displacement of [3H]PGF2alpha from full-length recombinant human FP receptor expressed in HEK293 cell membranes measured after 60 mins by scintillation counting method	ic50	0.0010	uM
7-[(1R,2R,3R,5S)-2-[(3R)-4-(3-chlorophenoxy)-3-hydroxybutyl]-3,5-dihydroxycyclopentyl]heptanoic acid	160700: Displacement of [3H]PGF2-alpha from human FP-receptor expressed in CHO-KI cells	ic50	0.0010	uM
5-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-4-(2-chloro-3,6-difluorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0011	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]cyclopentyl]hept-5-enoic acid	223522: In vitro binding at FP human prostaglandin receptor using [3H]PGF-2 alpha as radioligand	ic50	0.0020	uM
Dinoprost	160700: Displacement of [3H]PGF2-alpha from human FP-receptor expressed in CHO-KI cells	ic50	0.0025	uM
propan-2-yl (E)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]hept-5-enoate	246471: Efficacy for stimulation of prostanoid FP receptor-linked phosphoinositide turnover in Swiss 3T3 mouse fibroblast cells	ec50	0.0027	uM
7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-hydroxy-4-phenylsulfanylbutyl)cyclopentyl]heptanoic acid	161196: Affinity for human Prostanoid FP receptor expressed in COS-7 cells	ic50	0.0030	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]hept-5-enoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0036	uM
3-[(2S,5aR,6R,7R,8aS)-7-hydroxy-6-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-3,4,5,5a,6,7,8,8a-octahydro-2H-cyclopenta[b]oxepin-2-yl]propanoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0038	uM
5-[[2-(azepan-1-yl)-6-bromo-3-methylquinoline-4-carbonyl]amino]-4-(2-chlorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0040	uM
4-[(2R,4aR,5R,6R,7aS)-6-hydroxy-5-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]butanoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0041	uM
6-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-5-(2-chlorophenyl)hexanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0043	uM
5-[(6-bromo-3-methyl-2-piperidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0049	uM
6-bromo-N-[2-fluoro-4-(2H-tetrazol-5-yl)phenyl]-3-methyl-2-phenylquinoline-4-carboxamide	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0052	uM
3-fluoro-4-[(6-iodo-3-methyl-2-phenylquinoline-4-carbonyl)amino]benzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0060	uM
4-[(2S,4aR,5R,6R,7aS)-6-hydroxy-5-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]butanoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0071	uM
(4S)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0072	uM
5-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0079	uM
7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-[3-(trifluoromethyl)phenyl]pentyl]cyclopentyl]heptanoic acid	160699: Displacement of [3H]PGF-2 from human FP-receptor expressed in CHO-KI cells	ic50	0.0086	uM
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-3-(2-methoxyphenyl)butanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0090	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-[3-(trifluoromethyl)phenyl]pent-1-enyl]cyclopentyl]hept-5-enoic acid	160700: Displacement of [3H]PGF2-alpha from human FP-receptor expressed in CHO-KI cells	ic50	0.0100	uM
7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-hydroxy-4-thiophen-2-ylsulfanylbutyl)cyclopentyl]heptanoic acid	161196: Affinity for human Prostanoid FP receptor expressed in COS-7 cells	ic50	0.0110	uM
(4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0110	uM
7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-4-phenoxybutyl]cyclopentyl]heptanoic acid	161196: Affinity for human Prostanoid FP receptor expressed in COS-7 cells	ic50	0.0120	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]hept-5-enoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0120	uM
4-[(7-bromo-2-methyl-3-phenylnaphthalene-1-carbonyl)amino]-3-fluorobenzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0130	uM
(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0160	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4,4-dimethyloct-1-enyl]cyclopentyl]hept-5-enoic acid	160700: Displacement of [3H]PGF2-alpha from human FP-receptor expressed in CHO-KI cells	ic50	0.0160	uM
7-[(1R,2R,3R,5S)-2-[4-(3-chlorophenyl)sulfanyl-3-hydroxybutyl]-3,5-dihydroxycyclopentyl]heptanoic acid	161196: Affinity for human Prostanoid FP receptor expressed in COS-7 cells	ic50	0.0170	uM
4-[(6-bromo-3-chloro-2-phenylquinoline-4-carbonyl)amino]-3-fluorobenzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0170	uM
3-[(2R,5aR,6R,7R,8aS)-7-hydroxy-6-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-3,4,5,5a,6,7,8,8a-octahydro-2H-cyclopenta[b]oxepin-2-yl]propanoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0220	uM
4-[(3S,5aR,6R,7R,8aS)-6-[(E,3R)-4-(2,5-difluorophenoxy)-3-hydroxybut-1-enyl]-7-hydroxy-3,4,5,5a,6,7,8,8a-octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid	1939266: Agonist activity at FP receptor (unknown origin)	ec50	0.0223	uM
(Z)-8-[(2R,3S,4R)-2-[(E,3R)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-4-hydroxyoxolan-3-yl]oct-4-enoic acid	246471: Efficacy for stimulation of prostanoid FP receptor-linked phosphoinositide turnover in Swiss 3T3 mouse fibroblast cells	ec50	0.0230	uM
4-[(6-bromo-3-methyl-2-phenylquinolin-4-yl)methylamino]-3-fluorobenzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0250	uM
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-3-fluorobenzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0270	uM
4-[(6-bromo-3-cyclopropyl-2-phenylquinoline-4-carbonyl)amino]-3-fluorobenzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0270	uM
4-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-3,4,5,5a,6,7,8,8a-octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0280	uM
7-[(1R,2R,3R,5S)-2-[4-(3-fluorophenyl)sulfanyl-3-hydroxybutyl]-3,5-dihydroxycyclopentyl]heptanoic acid	161196: Affinity for human Prostanoid FP receptor expressed in COS-7 cells	ic50	0.0290	uM
2-[(2R,4aR,5R,6R,7aS)-6-hydroxy-5-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]-1,3-thiazole-4-carboxylic acid	1300200: Agonist activity at human FP receptor expressed in human Chem1 cells assessed as increase in intracellular calcium level by fluorescence based analysis	ec50	0.0320	uM
3-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-2-(2-chlorophenyl)propanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0320	uM
4-[(6-bromo-3-methyl-2-phenylquinoline-4-carbonyl)amino]-3-(2-chlorophenyl)butanoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0320	uM
(Z)-7-[(1R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-7-phenylhept-1-enyl]cyclopentyl]hept-5-enoic acid	155367: Binding potency towards PGF-2 alpha receptor (competitive binding) with natural [3H]-PGF 2 alpha in ovine luteal cells (OLC)	ic50	0.0320	uM
propan-2-yl (E)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate	246471: Efficacy for stimulation of prostanoid FP receptor-linked phosphoinositide turnover in Swiss 3T3 mouse fibroblast cells	ec50	0.0344	uM
4-[(6-bromo-3-methyl-1-oxo-2-phenylisoquinoline-4-carbonyl)amino]-3-fluorobenzoic acid	1677112: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay	ic50	0.0400	uM
7-[(1R,2R,3R,5S)-2-[(3R)-5-(3-fluorophenyl)-3-hydroxypentyl]-3,5-dihydroxycyclopentyl]heptanoic acid	160699: Displacement of [3H]PGF-2 from human FP-receptor expressed in CHO-KI cells	ic50	0.0420	uM
[(Z)-6-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]cyclopentyl]hex-4-enyl]-methylphosphinic acid	223522: In vitro binding at FP human prostaglandin receptor using [3H]PGF-2 alpha as radioligand	ic50	0.0420	uM
5-[(3S,5aR,6R,7R,8aS)-7-hydroxy-6-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-3,4,5,5a,6,7,8,8a-octahydro-2H-cyclopenta[b]oxepin-3-yl]pentanoic acid	1331417: Agonist activity at human prostaglandin FP receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0430	uM
(Z)-8-[(2R,3S,4R)-4-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]oxolan-3-yl]oct-4-enoic acid	246471: Efficacy for stimulation of prostanoid FP receptor-linked phosphoinositide turnover in Swiss 3T3 mouse fibroblast cells	ec50	0.0570	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	decreases expression	3
trichostatin A	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
fluprostenol	affects reaction, increases expression, increases reaction	1
diethyl phthalate	affects cotreatment, affects expression, affects reaction	1
diisononyl phthalate	affects cotreatment, affects expression, affects reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
diisobutyl phthalate	affects cotreatment, affects expression, affects reaction	1
butylbenzyl phthalate	affects cotreatment, affects expression, affects reaction	1
ferrous chloride	increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
clothianidin	decreases expression	1
abrine	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Asbestos	increases expression	1
Cadmium	increases expression, increases abundance	1
Calcitriol	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Dexamethasone	decreases expression	1

ChEMBL screening assays

104 unique, capped per target: 77 binding, 27 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009659	Binding	Inhibition of FP receptor	Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain. — Bioorg Med Chem Lett
CHEMBL1051804	Functional	Antagonist activity against prostaglandin F receptor	7-Azaindole-3-acetic acid derivatives: potent and selective CRTh2 receptor antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H368	293/FP/Galpha15	Transformed cell line	Female
CVCL_KU62	CHO-K1 PTGFR Gq	Spontaneously immortalized cell line	Female
CVCL_LB21	PathHunter U2OS PTGFR beta-arrestin	Cancer cell line	Female
CVCL_LB22	PathHunter U2OS PTGFR Total GPCR Internalization	Cancer cell line	Female
CVCL_YK57	U2OS PTGFR HiTSeeker	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis