SERPINE1

Summary

SERPINE1 (serpin family E member 1, HGNC:8583) is a protein-coding gene on chromosome 7q22.1, encoding Plasminogen activator inhibitor 1 (P05121). Serine protease inhibitor.

This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. The protein also functions as a component of innate antiviral immunity. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia.

Source: NCBI Gene 5054 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital plasminogen activator inhibitor type 1 deficiency (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 145 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000602

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8583
Approved symbol	SERPINE1
Name	serpin family E member 1
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PAI
Ensembl gene	ENSG00000106366
Ensembl biotype	protein_coding
OMIM	173360
Entrez	5054

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000223095, ENST00000870828, ENST00000950058, ENST00000950059, ENST00000950060, ENST00000950061, ENST00000950062, ENST00000950063

RefSeq mRNA: 12 — MANE Select: NM_000602 NM_000602, NM_001386456, NM_001386457, NM_001386458, NM_001386459, NM_001386460, NM_001386461, NM_001386462, NM_001386463, NM_001386464, NM_001386465, NM_001386466

CCDS: CCDS5711

Canonical transcript exons

ENST00000223095 — 9 exons

Exon	Start	End
ENSE00000712140	101130421	101130654
ENSE00000712144	101131875	101132069
ENSE00000712149	101133695	101133893
ENSE00000712153	101135494	101135594
ENSE00000712158	101135715	101135801
ENSE00000712164	101137001	101137084
ENSE00000881563	101128393	101128664
ENSE00001055519	101137405	101139247
ENSE00001714420	101127104	101127244

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 807.5330 / max 19971.0972, expressed in 1654 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80109	785.3003	1642
80113	3.2068	729
80118	2.7053	550
80112	2.5627	635
80117	2.4523	523
80116	2.0463	512
80110	1.8241	526
80136	1.5783	469
80139	1.4300	414
80111	1.2305	456

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	99.69	gold quality
stromal cell of endometrium	CL:0002255	99.57	gold quality
decidua	UBERON:0002450	99.38	gold quality
vein	UBERON:0001638	99.11	gold quality
saphenous vein	UBERON:0007318	98.92	gold quality
ascending aorta	UBERON:0001496	98.72	gold quality
thoracic aorta	UBERON:0001515	98.70	gold quality
gall bladder	UBERON:0002110	98.60	gold quality
aorta	UBERON:0000947	98.28	gold quality
descending thoracic aorta	UBERON:0002345	98.22	gold quality
pericardium	UBERON:0002407	98.14	gold quality
tibial artery	UBERON:0007610	98.06	gold quality
popliteal artery	UBERON:0002250	98.03	gold quality
right coronary artery	UBERON:0001625	97.76	gold quality
islet of Langerhans	UBERON:0000006	97.35	gold quality
right lung	UBERON:0002167	97.14	gold quality
placenta	UBERON:0001987	97.02	gold quality
left coronary artery	UBERON:0001626	96.83	gold quality
coronary artery	UBERON:0001621	96.71	gold quality
cartilage tissue	UBERON:0002418	95.71	gold quality
upper lobe of left lung	UBERON:0008952	95.33	gold quality
upper lobe of lung	UBERON:0008948	95.23	gold quality
type B pancreatic cell	CL:0000169	95.14	gold quality
smooth muscle tissue	UBERON:0001135	94.71	gold quality
olfactory bulb	UBERON:0002264	93.75	gold quality
mucosa of urinary bladder	UBERON:0001259	93.46	gold quality
omental fat pad	UBERON:0010414	93.25	gold quality
peritoneum	UBERON:0002358	93.20	gold quality
right ovary	UBERON:0002118	92.08	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.60	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	17060.92
E-CURD-7	yes	11583.24
E-ENAD-21	yes	11125.24
E-MTAB-8142	yes	6575.37
E-MTAB-8559	yes	4751.49
E-MTAB-6678	yes	2287.61
E-MTAB-8530	yes	1034.59
E-GEOD-130473	yes	945.90
E-ENAD-20	yes	469.28
E-GEOD-81608	yes	408.14
E-MTAB-7008	yes	129.87
E-MTAB-6701	yes	39.95
E-HCAD-31	yes	20.96
E-MTAB-5061	yes	11.65
E-GEOD-81547	yes	8.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ARNT, ATF3, BMAL1, BMAL2, CEBPA, CLOCK, CREB1, CRY1, E2F1, E2F2, E2F3, EGR1, ELK1, ELK3, EPAS1, ESR1, ESR2, ETS1, FOS, FOXC2, FOXD1, FOXG1, FOXO1, FOXO3, FOXO4, GATA6, GLI3, HIF1A, HLTF, HSF1, ID1, IRF6, JUN, JUNB, JUND, KDM5D, KLF10

miRNA regulators (miRDB)

118 targeting SERPINE1, 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-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mean transit time, the net quantitative turnover rate, and the sites of synthesis and catabolism (PMID:11734664)
• PAI-1 gene activation by TNF-alpha apparently is yet to be defined for the location of the response element and/or the signaling pathway. BAEC responded to TNF-alpha stimulation with activation of the MAP kinases and the NFkappaB transcriptional factors. (PMID:11776328)
• Plasminogen activator inhibitor type 1 promotes the self-association of vitronectin into complexes (PMID:11796716)
• Together with low birth weight, increased plasma PAI-1-act levels in early pubertal precocious pubarche may indicate a greater risk of developing hyperinsulinemic-hyperandrogenism features of polycystic ovary syndrome. (PMID:11809921)
• the 4G/5G polymorphism may influence PAI-1 expression in obesity, with a crucial role in central but not peripheral adiposity. (PMID:11816701)
• PAI-1/ tPA imbalance is associated with myocardial infarction at young age in Japanese men. (PMID:11816707)
• The expression of PAI-1 protein and PAI-1 mRNA is increased in HCC and contributes to the invasion, metastasis and prognosis of HCC. (PMID:11825444)
• Cell adhesion regulates plasminogen activator inhibitor-1 gene expression in anchorage-dependent cells; vitronectin and fibronectin, as components of ECM, may be the factors involved in the regulation of PAI-1 gene expression (PMID:11829481)
• Increased PAI-1 levels were found from eary 2d trimester through labor and decreased after delivery. Elevated PAI-1 serves to counteract the enhanced fibrinolysis seen during labor. (PMID:11858184)
• In children with sepsis-induced multiple organ failure, a cytokine-associated increase in circulating PAI-1 release & systemic activity was predicted. Increased PAI-1 activity was associated with cardiovascular, renal, and hepatic failure. (PMID:11858480)
• Arsenite inhibited the thrombomodulin (TM) mRNA expression and reduced the TM antigen level in microvascular endothelial cells, but not umbilical vein endothelial cells, suggesting a role in Blackfoot disease, a peripheral vascular occlusive disease. (PMID:11864708)
• Identification of a tightly regulated hypoxia-response element in the promoter of human plasminogen activator inhibitor-1. (PMID:11877282)
• PAI-1 inhibits plasminogen activators by forming stable complexes endocytosed by LDL receptor superfamily mechanism and circulates in plasma and latently in platelets but is also secreted and deposited into matrix by cells to participate in tissue repair. (PMID:11909993)
• TGFbeta was the only growth factor tested that was able to exceptionally up-regulate PAI-1, mainly in dystrophic satellite cells rather than normal myoblasts. (PMID:11928807)
• PAI-1 was determined in myocardial infarction and re-infarction patients along with other parameters relevant for the Syndrome X. (PMID:11934213)
• polymorphic in graft dysfunction after renal transplantation (PMID:11981424)
• a decreased risk of MI or stroke among young women carrying the 4G allele of the PAI-1 4G/5G polymorphism. (PMID:12006921)
• The common -675 4G/5G polymorphism is strongly associated with obesity (PMID:12032637)
• inhibition of Rho/Rho-kinase signaling downregulates the synthesis of PAI-1 in human monocytes (PMID:12063175)
• Hypoxia enhances the expression of plasminogen activator inhibitor-1 (PMID:12086154)
• PAI-1 is induced by oncostatin M in lung tumor cells (PMID:12090757)
• C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils. (PMID:12091343)
• Hyperglycemic siblings of type II diabetic patients have increased blood levels, central obeisty and insulin resistance compared with their paired normoglycaemic sibling. (PMID:12107743)
• PAI-1 also plays a pivotal role in progressive renal disease, both glomerulosclerosis and tubulointerstitial fibrosis. (PMID:12110504)
• interactions between the fibrinolytic and renin-angiotensin systems play an important role in the genetic architecture of plasma t-PAI-1 (PMID:12123488)
• Human breast adenocarcinoma cell lines promote angiogenesis by providing cells with uPA-PAI-1 and by enhancing their expression. (PMID:12124797)
• relationships among adult periodontitis, smoking, and a variation in the deletion/insertion (4G/5G) promoter polymorphism of the plasminogen-activator-inhibitor-1 (PAI-1) gene (PMID:12140748)
• upregulation of PAI-1, uPA, and tPA after long-term LDL exposure seems to be mediated by a delayed PKC activation associated with an increased PA inhibitory activity (PMID:12167592)
• study demonstrates that PAI-1 concentrations are higher in impaired glucose tolerance than in normal glucose tolerance subjects (PMID:12181379)
• There was a positive correlation between uPA and PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001 and p = 0.01, respectively) (PMID:12218297)
• plasminogen activator inhibitor 1 (PAI-1) is converted by monoclonal antibodies to a substrate for tissue (tPA)- and urokinase plasminogen activators (PMID:12223472)
• Both adipose tissue and blood PAI-1 levels were positively associated with TNFRSF1A and TNFRSF1B in obesity. (PMID:12353079)
• Study of the association between 4G/4G and 4G/5G genotypes and the site of thrombosis suggests an association with thrombosis in vessels of internal organs especially in the portal veins. (PMID:12353306)
• formation of an inhibited serpin-proteinase complex as a single concerted transition of the serpin structure (PMID:12356300)
• plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G polymorphism is associated with coronary heart disease (CHD) in Chinese (PMID:12362314)
• Oncostatin M and interleukin-1 regulate the PAI-1 gene expression via up-regulating c-fos levels and subsequent binding of c-fos/c-jun heterodimers to the proximal element of the PAI-1 gene. (PMID:12390531)
• The morning increase in PAI-1 is more pronounced among homozygotes for the 4G allele compared with the other genotypes. Homozygosity for the 4G allele is associated with increased PAI-1 levels during the morning only. (PMID:12406875)
• diurnal pattern in PAI-1 activity and t-PA in relation to the 4G/5G-polymorphism in the promoter of the PAI-1 gene (PMID:12428096)
• findings suggest that PAI-1 plays a role in later (thrombotic) rather than an earlier (atherosclerotic) stage of cardiovascular disease process. (PMID:12431476)
• REVIEW: studies defining the binding sites of vitronectin and PAI-1 and binding affinities in the formation of larger PAI-1/Vtn complexes. (PMID:12437099)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	serpine1	ENSDARG00000056795
mus_musculus	Serpine1	ENSMUSG00000037411
rattus_norvegicus	Serpine1	ENSRNOG00000001414

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Plasminogen activator inhibitor 1 — P05121 (reviewed: P05121)

Alternative names: Endothelial plasminogen activator inhibitor, Serpin E1

All UniProt accessions (1): P05121

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease inhibitor. Inhibits TMPRSS7. Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots. As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading. Acts as a regulator of cell migration, independently of its role as protease inhibitor. It is required for stimulation of keratinocyte migration during cutaneous injury repair. It is involved in cellular and replicative senescence. Plays a role in alveolar type 2 cells senescence in the lung. Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis.

Subunit / interactions. Forms a heterodimer with TMPRSS7. Interacts with VTN. Binds LRP1B; binding is followed by internalization and degradation. Interacts with PPP1CB. In complex with PLAU/uPA, interacts with PLAUR/uPAR. Interacts with SORL1 and LRP1, either alone or in complex with PLAU; these interactions are abolished in the presence of LRPAP1/RAP. The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORL1. Interacts with PLAT/tPA. Also interacts with SORL1, when complexed to PLAT/tPA.

Subcellular location. Secreted.

Tissue specificity. Expressed in endothelial cells. Found in plasma, platelets, and hepatoma and fibrosarcoma cells.

Post-translational modifications. Inactivated by proteolytic attack of the urokinase-type (u-PA) and the tissue-type (TPA), cleaving the 369-Arg-|-Met-370 bond.

Disease relevance. Plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:613329] A hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen. The disease is caused by variants affecting the gene represented in this entry. A rare PAI-1D mutation resulting in a frameshift and protein truncation has been found in an Old Order Amish community. Homozygous mutation carriers suffer from episodes of major hemorrhage, while heterozygous carriers do not manifest abnormal bleeding. Heterozygosity for the mutation is associated with longer leukocyte telomere length, lower fasting insulin levels, lower prevalence of diabetes mellitus, and a longer life span.

Induction. Up-regulated by coagulation factor Xa (F10) in atrial tissues. Up-regulated in atrial tissues by rapid pacing resembling atrial fibrillation.

Similarity. Belongs to the serpin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05121-1	1	yes
P05121-2	2

RefSeq proteins (12): NP_000593, NP_001373385, NP_001373386, NP_001373387, NP_001373388, NP_001373389, NP_001373390, NP_001373391, NP_001373392, NP_001373393, NP_001373394, NP_001373395 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (61 total): strand 19, helix 14, turn 8, sequence conflict 6, sequence variant 5, glycosylation site 3, mutagenesis site 2, signal peptide 1, chain 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
7AQF	X-RAY DIFFRACTION	1.77
1LJ5	X-RAY DIFFRACTION	1.8
6ZRV	X-RAY DIFFRACTION	1.88
1A7C	X-RAY DIFFRACTION	1.95
3CVM	X-RAY DIFFRACTION	2.02
6GWN	X-RAY DIFFRACTION	2.03
1DVN	X-RAY DIFFRACTION	2.1
4G8R	X-RAY DIFFRACTION	2.19
7AQG	X-RAY DIFFRACTION	2.27
1OC0	X-RAY DIFFRACTION	2.28
6GWP	X-RAY DIFFRACTION	2.28
3PB1	X-RAY DIFFRACTION	2.3
3Q02	X-RAY DIFFRACTION	2.3
4IC0	X-RAY DIFFRACTION	2.32
6GWQ	X-RAY DIFFRACTION	2.32
1DVM	X-RAY DIFFRACTION	2.4
4AQH	X-RAY DIFFRACTION	2.4
3UT3	X-RAY DIFFRACTION	2.42
1C5G	X-RAY DIFFRACTION	2.6
3EOX	X-RAY DIFFRACTION	2.61
3Q03	X-RAY DIFFRACTION	2.64
1DB2	X-RAY DIFFRACTION	2.7
3R4L	X-RAY DIFFRACTION	2.7
9PAI	X-RAY DIFFRACTION	2.7
4G8O	X-RAY DIFFRACTION	2.71
6I8S	X-RAY DIFFRACTION	2.9
1B3K	X-RAY DIFFRACTION	2.99
5BRR	X-RAY DIFFRACTION	3.16
5ZLZ	X-RAY DIFFRACTION	3.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05121-F1	89.68	0.82

Antibody-complex structures (SAbDab): 6 — 6GWN, 6GWP, 6GWQ, 6I8S, 6ZRV, 7AQG

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): 369–370 (reactive bond)

Glycosylation sites (3): 232, 288, 352

Mutagenesis-validated functional residues (2):

Position	Phenotype
197	increased half-life of the active form when associated with c-355.
355	increased half-life of the active form when associated with c-197.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-3000178	ECM proteoglycans
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-9735871	SARS-CoV-1 targets host intracellular signalling and regulatory pathways

MSigDB gene sets: 722 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION

GO Biological Process (30): angiogenesis (GO:0001525), negative regulation of plasminogen activation (GO:0010757), negative regulation of smooth muscle cell migration (GO:0014912), positive regulation of blood coagulation (GO:0030194), negative regulation of blood coagulation (GO:0030195), negative regulation of cell migration (GO:0030336), positive regulation of interleukin-8 production (GO:0032757), negative regulation of cell adhesion mediated by integrin (GO:0033629), positive regulation of leukotriene production involved in inflammatory response (GO:0035491), fibrinolysis (GO:0042730), positive regulation of angiogenesis (GO:0045766), negative regulation of proteolysis (GO:0045861), positive regulation of receptor-mediated endocytosis (GO:0048260), positive regulation of inflammatory response (GO:0050729), positive regulation of coagulation (GO:0050820), defense response to Gram-negative bacterium (GO:0050829), negative regulation of fibrinolysis (GO:0051918), negative regulation of vascular wound healing (GO:0061044), negative regulation of wound healing (GO:0061045), negative regulation of thrombin-activated receptor signaling pathway (GO:0070495), cellular response to lipopolysaccharide (GO:0071222), positive regulation of monocyte chemotaxis (GO:0090026), replicative senescence (GO:0090399), dentinogenesis (GO:0097187), positive regulation of odontoblast differentiation (GO:1901331), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), negative regulation of smooth muscle cell-matrix adhesion (GO:2000098), negative regulation of endothelial cell apoptotic process (GO:2000352), negative regulation of integrin-mediated signaling pathway (GO:2001045), response to bacterium (GO:0009617)

GO Molecular Function (6): protease binding (GO:0002020), endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), signaling receptor binding (GO:0005102), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062), serine protease inhibitor complex (GO:0097180), peptidase inhibitor complex (GO:1904090)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	2
Response to elevated platelet cytosolic Ca2+	1
Circadian clock	1
Extracellular matrix organization	1
Hemostasis	1
Coagulation pathway	1
MITF-M-dependent gene expression	1
SARS-CoV-1-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood coagulation	2
regulation of blood coagulation	2
negative regulation of wound healing	2
positive regulation of multicellular organismal process	2
positive regulation of response to external stimulus	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of plasminogen activation	1
negative regulation of protein processing	1
plasminogen activation	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
negative regulation of cell migration	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
negative regulation of coagulation	1
negative regulation of hemostasis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
negative regulation of cell adhesion	1
cell adhesion mediated by integrin	1
regulation of cell adhesion mediated by integrin	1
leukotriene production involved in inflammatory response	1
regulation of leukotriene production involved in inflammatory response	1
positive regulation of inflammatory response	1
negative regulation of blood coagulation	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
proteolysis	1
regulation of proteolysis	1
negative regulation of protein metabolic process	1
receptor-mediated endocytosis	1
positive regulation of endocytosis	1
regulation of receptor-mediated endocytosis	1

Protein interactions and networks

STRING

3750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINE1	PLAT	P00750	999
SERPINE1	PLAU	P00749	999
SERPINE1	VTN	P01141	997
SERPINE1	PLAUR	Q03405	984
SERPINE1	LRP1	Q07954	984
SERPINE1	PLG	P00747	978
SERPINE1	CCL2	P13500	895
SERPINE1	F3	P13726	887
SERPINE1	VLDLR	P98155	885
SERPINE1	MMP3	P08254	861
SERPINE1	LEP	P41159	851
SERPINE1	INS	P01308	848
SERPINE1	THBD	P07204	839
SERPINE1	HGF	P14210	825
SERPINE1	VWF	P04275	816

IntAct

74 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
SERPINE1	SGTA	psi-mi:“MI:0915”(physical association)	0.720
SERPINE1	SGTB	psi-mi:“MI:0915”(physical association)	0.720
SGTA	SERPINE1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SERPINE1	PLAU	psi-mi:“MI:0915”(physical association)	0.700
SERPINE1	PLAU	psi-mi:“MI:0407”(direct interaction)	0.700
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
SERPINE1	VTN	psi-mi:“MI:0407”(direct interaction)	0.590
UBQLN1	SERPINE1	psi-mi:“MI:0915”(physical association)	0.560
SERPINE1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
SERPINE1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SERPINE1	PITX1	psi-mi:“MI:0915”(physical association)	0.560
SERPINE1	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
TLX3	SERPINE1	psi-mi:“MI:0915”(physical association)	0.560
SERPINE1	HSD17B11	psi-mi:“MI:0915”(physical association)	0.560
SERPINE1	ORM1	psi-mi:“MI:0403”(colocalization)	0.540
ORM1	SERPINE1	psi-mi:“MI:0403”(colocalization)	0.540

BioGRID (64): SGTA (Two-hybrid), UBQLN1 (Two-hybrid), SGTB (Two-hybrid), SERPINE1 (Two-hybrid), SERPINE1 (Reconstituted Complex), SERPINE1 (Co-localization), SERPINE1 (Affinity Capture-Western), SERPINE1 (Positive Genetic), SERPINE1 (Reconstituted Complex), SERPINE1 (Co-fractionation), ANP32A (Affinity Capture-MS), ERP29 (Affinity Capture-MS), GANAB (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), SERPINE1 (Two-hybrid)

ESM2 similar proteins: A2I7N3, B0UYL8, O75830, P01015, P01017, P01019, P05121, P05154, P05155, P05544, P05545, P05546, P07759, P09006, P11859, P13909, P20757, P20961, P22777, P29622, P31211, P32759, P47776, P49182, P50448, P50449, P70458, P79335, P97290, Q03734, Q5I2A0, Q5RCR2, Q5RDA8, Q60396, Q62975, Q63556, Q64268, Q6P4P1, Q6P734, Q7TMF5

Diamond homologs: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A5PJK0, A6QPQ2, A9RA96, B0CMB0, B1MTC3, B2D1U1, B2KI30, B3RFC3, B4USX2, E2RVI8, O08800, O35684, O73790, O73860, O75830, P01008, P01012, P01014, P05120, P05121, P05154, P05619, P07092, P07093, P07759, P09006, P12388, P13909, P14754, P17475, P29508

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
SNAI1	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
CLOCK/BMAL1	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
CLOCK/BMAL2	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
SRF	“down-regulates quantity by repression”	SERPINE1	“transcriptional regulation”
SERPINE1	up-regulates	Fibrosis
N	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
TGFBR1	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
SERPINE1	“down-regulates activity”	F12	binding
SERPINE1	down-regulates	Fibrinolysis
miR-642a-3p	“down-regulates quantity by destabilization”	SERPINE1	“post transcriptional regulation”
SMAD3/SMAD4	“up-regulates quantity by expression”	SERPINE1	“transcriptional regulation”
SERPINE1	up-regulates	Cell_adhesion

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	5	21.6×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	93
Likely benign	13
Benign	22

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
13571	NM_000602.5(SERPINE1):c.699_700del (p.Tyr233_Thr234insTer)	Pathogenic
627494	NC_000007.14:g.101127040_101127295del	Likely pathogenic

SpliceAI

635 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101127243:AGGT:A	donor_loss	1.0000
7:101127245:GTAG:G	donor_loss	1.0000
7:101127246:T:G	donor_loss	1.0000
7:101130408:T:TA	acceptor_gain	1.0000
7:101130413:C:CA	acceptor_gain	1.0000
7:101130414:G:A	acceptor_gain	1.0000
7:101130415:GTGCA:G	acceptor_gain	1.0000
7:101130419:A:AG	acceptor_gain	1.0000
7:101130419:A:T	acceptor_loss	1.0000
7:101130420:G:GA	acceptor_gain	1.0000
7:101130420:GA:G	acceptor_gain	1.0000
7:101130420:GAC:G	acceptor_gain	1.0000
7:101130420:GACA:G	acceptor_gain	1.0000
7:101130420:GACAA:G	acceptor_gain	1.0000
7:101130653:AGGTG:A	donor_loss	1.0000
7:101130654:GGTG:G	donor_loss	1.0000
7:101130655:G:GA	donor_loss	1.0000
7:101131873:A:AG	acceptor_gain	1.0000
7:101131873:AG:A	acceptor_gain	1.0000
7:101131874:G:GA	acceptor_gain	1.0000
7:101131874:GG:G	acceptor_gain	1.0000
7:101131874:GGT:G	acceptor_gain	1.0000
7:101131874:GGTA:G	acceptor_gain	1.0000
7:101131874:GGTAT:G	acceptor_gain	1.0000
7:101132065:CTATA:C	donor_gain	1.0000
7:101132066:TATA:T	donor_gain	1.0000
7:101132066:TATAG:T	donor_loss	1.0000
7:101132067:ATA:A	donor_gain	1.0000
7:101132068:TA:T	donor_gain	1.0000
7:101132069:AGTAA:A	donor_loss	1.0000

AlphaMissense

2655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101131961:T:A	W198R	0.997
7:101131961:T:C	W198R	0.997
7:101131963:G:C	W198C	0.997
7:101131963:G:T	W198C	0.997
7:101132003:T:C	F212L	0.994
7:101132005:C:A	F212L	0.994
7:101132005:C:G	F212L	0.994
7:101133847:T:A	W285R	0.993
7:101133847:T:C	W285R	0.993
7:101137054:T:C	F381L	0.993
7:101137056:C:A	F381L	0.993
7:101137056:C:G	F381L	0.993
7:101131962:G:C	W198S	0.992
7:101131973:T:C	F202L	0.991
7:101131975:C:A	F202L	0.991
7:101131975:C:G	F202L	0.991
7:101133740:T:C	L249P	0.990
7:101132004:T:C	F212S	0.989
7:101133849:G:C	W285C	0.988
7:101133849:G:T	W285C	0.988
7:101133890:C:A	P299H	0.988
7:101137070:G:C	R386P	0.988
7:101131974:T:G	F202C	0.987
7:101133776:C:A	A261D	0.987
7:101135558:T:C	F322L	0.987
7:101135560:C:A	F322L	0.987
7:101135560:C:G	F322L	0.987
7:101132004:T:G	F212C	0.986
7:101130594:T:C	F149L	0.985
7:101130596:T:A	F149L	0.985

dbSNP variants (sampled 300 via entrez): RS1000050686 (7:101128780 G>A), RS1000112229 (7:101130439 C>A), RS1000112913 (7:101128389 C>T), RS1000143043 (7:101139226 T>A,G), RS1000400387 (7:101133068 T>C,G), RS1000828592 (7:101133956 G>A,T), RS1001216515 (7:101135365 C>T), RS1001678297 (7:101129798 C>T), RS1001723418 (7:101132072 A>G), RS1002005106 (7:101131330 C>T), RS1002147273 (7:101136809 A>G), RS1002248598 (7:101126336 A>T), RS1003515213 (7:101127415 A>T), RS1003674434 (7:101132615 G>A), RS1003795024 (7:101129658 G>A)

Disease associations

OMIM: gene MIM:173360 | disease phenotypes: MIM:613329

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital plasminogen activator inhibitor type 1 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital plasminogen activator inhibitor type 1 deficiency	Definitive	AR

Mondo (1): congenital plasminogen activator inhibitor type 1 deficiency (MONDO:0013227)

Orphanet (1): Congenital plasminogen activator inhibitor type 1 deficiency (Orphanet:465)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0001058	Poor wound healing
HP:0001622	Premature birth
HP:0001685	Myocardial fibrosis
HP:0001892	Abnormal bleeding
HP:0001933	Subcutaneous hemorrhage
HP:0001934	Persistent bleeding after trauma
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0003577	Congenital onset
HP:0004846	Prolonged bleeding after surgery
HP:0005261	Joint hemorrhage
HP:0005268	Miscarriage
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0011854	Hemoperitoneum
HP:0011891	Post-partum hemorrhage
HP:0012233	Intramuscular hematoma
HP:0030657	Umbilical cord hematoma
HP:0040184	Oral bleeding
HP:0040228	Decreased level of plasminogen
HP:0040230	Decreased level of tissue plasminogen activator
HP:0040245	Reduced alpha-2-antiplasmin activity
HP:0040248	Reduced plasminogen activator inhibitor 1 activity
HP:0040249	Reduced plasminogen activator inhibitor 1 antigen
HP:0100310	Epidural hemorrhage

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001684_2	Plasminogen activator inhibitor type 1 levels (PAI-1)	3.000000e-24
GCST002374_5	Plasma plasminogen activator levels	3.000000e-06
GCST006585_2677	Blood protein levels	1.000000e-06
GCST007250_7	Nonunion in individuals with fractures	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004792	plasminogen activator inhibitor 1 measurement
EFO:0009707	fractures, ununited

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567640	Plasminogen Activator Inhibitor-1 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3475 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 147 (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
CHEMBL325424	ALEPLASININ	2	35
CHEMBL325441	TIPLASININ	2	112

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1799889	Efficacy	3	antidepressants;citalopram;fluoxetine	Major Depressive Disorder
rs2227631	Efficacy	3	antidepressants;citalopram;fluoxetine	Major Depressive Disorder
rs6092	Toxicity	3	dexamethasone	Acute lymphoblastic leukemia

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6092	SERPINE1	3	2.75	1	dexamethasone
rs7242	SERPINE1		0.00	0
rs1799889	SERPINE1	3	2.00	1	antidepressants;citalopram;fluoxetine
rs2227631	SERPINE1	3	2.00	1	antidepressants;citalopram;fluoxetine
rs2227684	SERPINE1		0.00	0

Binding affinities (BindingDB)

176 measured of 179 human assays (180 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CDE-082	KD	5.3 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
Tannic Acid, A	IC50	7 nM
[(2R,3R,4S,5R)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
[(2R,3R,4S,5S,6S)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
[(2R,3S,4S,5R,6R)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
[(2R,3S,4S,5R,6S)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
CDE-066	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
N-(3,4-dihydroxyphenyl)sulfonyl-N-heptyl-3,4-dihydroxybenzenesulfonamide	IC50	33 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
[2-(3,4-dihydroxybenzoyl)oxy-3-[[3-(trifluoromethyl)phenyl]sulfonylamino]propyl] 3,4-dihydroxybenzoate	IC50	35 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
[(1R,3S)-3-(3,4,5-trihydroxybenzoyl)oxycyclohexyl] 3,4,5-trihydroxybenzoate	IC50	50 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
[4-(3,4,5-trihydroxybenzoyl)oxycyclohexyl] 3,4,5-trihydroxybenzoate	IC50	50 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
N-[2-(3,4-dihydroxyphenyl)ethyl]-3,4-dihydroxybenzenesulfonamide	IC50	51 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
[3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(3,4,5-trihydroxybenzoyl)oxypropyl] 3,4,5-trihydroxybenzoate	IC50	70 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
N’-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxybenzenesulfonohydrazide	IC50	90 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
HEXACHLOROPHENE	IC50	98.3 nM
N-(3,4-dihydroxyphenyl)sulfonyl-N-(4-hexylphenyl)-3,4-dihydroxybenzenesulfonamide	IC50	120 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(benzenesulfonyl)-N-[2-(3,4-dihydroxyphenyl)ethyl]-3,4-dihydroxybenzenesulfonamide	IC50	173 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxy-N-nonylbenzenesulfonamide	IC50	180 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
CDE-031	IC50	280 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
CDE-008	IC50	370 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
N-[2-[(3,4-dihydroxyphenyl)sulfonyl-nonylamino]ethyl]-3,4-dihydroxy-N-nonylbenzenesulfonamide	IC50	420 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-[2-[decyl-(3,4-dihydroxyphenyl)sulfonylamino]ethyl]-3,4-dihydroxy-N-methylbenzenesulfonamide	IC50	450 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxy-N-(4-phenylphenyl)benzenesulfonamide	IC50	510 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-[2-[(3,4-dihydroxyphenyl)sulfonyl-heptylamino]ethyl]-N-heptyl-3,4-dihydroxybenzenesulfonamide	IC50	590 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxy-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide	IC50	611 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-[2-[(3,4-dihydroxyphenyl)sulfonyl-octylamino]ethyl]-3,4-dihydroxy-N-octylbenzenesulfonamide	IC50	620 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(4-hexylphenyl)-3,4-dihydroxybenzenesulfonamide	IC50	910 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(3,4-dihydroxyphenyl)sulfonyl-N-(4-dodecylphenyl)-3,4-dihydroxybenzenesulfonamide	IC50	920 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxy-N-phenylbenzenesulfonamide	IC50	1020 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
CHEMBL4207363	IC50	1170 nM
CDE-034	IC50	1170 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
3,4-dihydroxy-N-octyl-N-(4-pentylphenyl)sulfonylbenzenesulfonamide	IC50	1280 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-hexyl-3,4-dihydroxy-N-octylbenzenesulfonamide	IC50	1340 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N,N-dihexyl-3,4-dihydroxybenzenesulfonamide	IC50	1670 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
4-[2-(3,4-dihydroxyphenyl)sulfonyldiazinan-1-yl]sulfonylbenzene-1,2-diol	IC50	1710 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
6-[(3,4-dihydroxyphenyl)sulfonylamino]hexanoic acid	IC50	1820 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
CHEMBL4202481	IC50	1860 nM
N-[(3,5-dichloro-4-hydroxyphenyl)methyl]-3,4-dihydroxy-N-octylbenzenesulfonamide	IC50	1980 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-decyl-N-[2-[decyl-(3,4-dihydroxyphenyl)sulfonylamino]ethyl]-3,4-dihydroxybenzenesulfonamide	IC50	1980 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-(4-hexylphenyl)-3,4-dihydroxy-N-(4-propylphenyl)sulfonylbenzenesulfonamide	IC50	2290 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
3,4-dihydroxy-N-octyl-N-[[3-(trifluoromethyl)phenyl]methyl]benzenesulfonamide	IC50	2400 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
CDE-056	IC50	2960 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
3,4-dihydroxy-N-(4-hydroxyphenyl)sulfonyl-N-octylbenzenesulfonamide	IC50	4340 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
(5Z)-3-[(3-bromophenyl)methyl]-5-[(3,4-dihydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione	IC50	4960 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
4-(2,3-dihydroindol-1-ylsulfonyl)benzene-1,2-diol	IC50	5050 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
N-[(3-chlorophenyl)methyl]-3,4-dihydroxy-N-octylbenzenesulfonamide	IC50	5110 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
(5Z)-3-benzyl-5-[(3,4-dihydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione	IC50	5360 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
3,4-dihydroxy-N,N-dioctylbenzenesulfonamide	IC50	5490 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
3,4-dihydroxy-N-(2-hydroxy-2-phenylethyl)-N-octylbenzenesulfonamide	IC50	6740 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
4-[(2R)-2-(2-phenylethyl)pyrrolidin-1-yl]sulfonylbenzene-1,2-diol	IC50	6980 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof

ChEMBL bioactivities

224 potent at pChembl≥5 of 293 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.51	Kd	3.1	nM	CHEMBL3669202
8.28	Kd	5.3	nM	CHEMBL3669203
8.00	IC50	10	nM	CHEMBL425946
8.00	IC50	10	nM	CHEMBL377052
8.00	IC50	10	nM	CHEMBL207014
8.00	IC50	10	nM	CHEMBL1224764
8.00	IC50	10	nM	CHEMBL3669202
8.00	IC50	10	nM	CHEMBL419935
8.00	IC50	10	nM	CHEMBL112242
7.64	Kd	23	nM	CHEMBL2087114
7.51	Kd	31	nM	CHEMBL2087115
7.41	IC50	39	nM	CHEMBL295987
7.30	IC50	50	nM	CHEMBL3669191
7.30	IC50	50	nM	CHEMBL3669189
7.29	Kd	51	nM	CHEMBL1090448
7.17	Kd	67	nM	CHEMBL2087116
7.16	IC50	70	nM	CHEMBL3669200
7.05	IC50	90	nM	CHEMBL3669193
7.00	IC50	100	nM	CHEMBL47330
7.00	IC50	100	nM	CHEMBL295776
7.00	IC50	100	nM	CHEMBL325164
7.00	IC50	100	nM	CHEMBL114144
7.00	IC50	100	nM	CHEMBL112371
6.89	IC50	130	nM	CHEMBL45498
6.85	IC50	140	nM	CHEMBL295222
6.70	IC50	200	nM	CHEMBL10062
6.70	IC50	200	nM	CHEMBL87654
6.66	IC50	220	nM	CHEMBL298263
6.62	IC50	240	nM	CHEMBL43826
6.58	IC50	260	nM	CHEMBL87654
6.57	IC50	270	nM	CHEMBL300075
6.55	IC50	280	nM	CHEMBL2087115
6.55	IC50	284	nM	CHEMBL596879
6.54	IC50	290	nM	CHEMBL10004
6.52	IC50	300	nM	CHEMBL77246
6.52	IC50	300	nM	CHEMBL10181
6.52	IC50	300	nM	CHEMBL275779
6.43	IC50	370	nM	CHEMBL2087114
6.42	IC50	380	nM	CHEMBL419935
6.41	IC50	390	nM	CHEMBL86652
6.40	IC50	400	nM	CHEMBL114144
6.33	IC50	470	nM	CHEMBL47879
6.32	IC50	480	nM	CHEMBL296520
6.30	IC50	500	nM	CHEMBL10014
6.30	IC50	500	nM	CHEMBL349130
6.30	IC50	500	nM	CHEMBL111847
6.29	IC50	510	nM	CHEMBL10240
6.29	IC50	510	nM	CHEMBL10062
6.29	IC50	510	nM	CHEMBL87654
6.28	IC50	520	nM	CHEMBL86470

PubChem BioAssay actives

215 with measured affinity, of 469 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,3S,4S,5R)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	kd	0.0031	uM
2,3-bis[(3,4,5-trihydroxybenzoyl)oxy]propyl 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	kd	0.0053	uM
[2,3-dihydroxy-5-[[3,4,5,6-tetrakis[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]oxan-2-yl]methoxycarbonyl]phenyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0070	uM
1-[3-[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]-4-nitrophenyl]piperidine-4-carboxylic acid	158354: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined using plasma clot lysis assay	ic50	0.0100	uM
4-[3-[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]-4-nitrophenoxy]benzoic acid	158354: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined using plasma clot lysis assay	ic50	0.0100	uM
2-(3,4,5-trihydroxybenzoyl)oxyethyl 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	kd	0.0230	uM
[(1R,2S)-2-(3,4,5-trihydroxybenzoyl)oxycyclohexyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	kd	0.0310	uM
(E)-3-[3-(4-chlorophenoxy)-5,6-bis[(4-phenylsulfanylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.0390	uM
[2-(3,4,5-trihydroxybenzoyl)oxyphenyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	kd	0.0510	uM
[(1R,2R)-2-(3,4,5-trihydroxybenzoyl)oxycyclohexyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	kd	0.0670	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0910	uM
(E)-3-[3-(4-chlorophenoxy)-5,6-bis[(4-phenoxyphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.1000	uM
2-[2-methoxy-6-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]phenoxy]-5-nitrobenzoic acid	158354: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined using plasma clot lysis assay	ic50	0.1000	uM
3-[3-[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]-4-nitrophenoxy]benzoic acid	158354: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined using plasma clot lysis assay	ic50	0.1000	uM
9-hydroxy-3-methoxy-4,7-dimethyl-10-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]-6-oxobenzo[b][1,4]benzodioxepine-1-carboxylic acid	158354: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined using plasma clot lysis assay	ic50	0.1000	uM
(E)-3-[3-phenoxy-5,6-bis[(4-phenylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.1000	uM
(E)-3-[3-(4-chlorophenoxy)-5,6-bis[(4-phenylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.1300	uM
(E)-3-[3-(4-chlorophenoxy)-5,6-bis[[4-(4-methoxyphenyl)phenyl]methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.1400	uM
8-[4-[(E)-[(5Z)-3,6-dioxo-5-[[4-(thiophene-2-carbonylamino)phenyl]methylidene]piperazin-2-ylidene]methyl]phenoxy]octanoic acid	225437: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by chromogenic assay.	ic50	0.2000	uM
8-[4-[(Z)-[(5Z)-3,6-dioxo-5-[[4-(thiophene-2-carbonylamino)phenyl]methylidene]piperazin-2-ylidene]methyl]phenoxy]octanoic acid	158357: Inhibitory activity of compound against Plasminogen activator inhibitor-1	ic50	0.2000	uM
(E)-3-[3-(4-chlorophenoxy)-5,6-bis[(3-phenylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.2200	uM
(E)-3-[3-(3-fluorophenoxy)-5,6-bis[(4-phenylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.2400	uM
(E)-3-[5,6-bis[(4-benzylphenyl)methoxy]-3-(4-chlorophenoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.2700	uM
N-(3,4-dihydroxyphenyl)sulfonyl-N-hexyl-3,4-dihydroxybenzenesulfonamide	456917: Inhibition of human recombinant PAI1 assessed as rate of AMC release after 30 mins	ic50	0.2840	uM
6-(1-benzothiophen-2-yl)-4-hydroxy-2-oxo-N-[4-[7-(tetrazol-1-yl)heptoxy]phenyl]-1H-quinoline-3-carboxamide	225438: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by complex assay.	ic50	0.2900	uM
(3Z,6Z)-3-(pyridin-2-ylmethylidene)-6-[[4-(3-pyridin-3-ylpropoxy)phenyl]methylidene]piperazine-2,5-dione	158356: Inhibitory concentration required against Plasminogen activator inhibitor 1.	ic50	0.3000	uM
8-[4-[[7-(1-benzothiophen-2-yl)-4-hydroxy-2-oxo-1H-quinoline-3-carbonyl]amino]phenoxy]octanoic acid	225437: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by chromogenic assay.	ic50	0.3000	uM
1-(4-chlorophenyl)-3-hydroxy-5-oxo-N-[4-[7-(tetrazol-1-yl)heptoxy]phenyl]-2H-pyrrole-4-carboxamide	225438: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by complex assay.	ic50	0.3000	uM
[(2R,3R)-7-hydroxy-5-(3,4,5-trihydroxybenzoyl)oxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.3300	uM
10-[4-[(Z)-[(5Z)-3,6-dioxo-5-[[4-(thiophene-2-carbonylamino)phenyl]methylidene]piperazin-2-ylidene]methyl]anilino]-10-oxodecanoic acid	158357: Inhibitory activity of compound against Plasminogen activator inhibitor-1	ic50	0.3900	uM
methyl (E)-3-[3-(4-chlorophenoxy)-5,6-bis(phenylmethoxy)-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoate	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.4700	uM
(E)-3-[3-(4-chloro-3-methylphenoxy)-5,6-bis[(4-phenylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.4800	uM
2-[2-methoxy-6-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]phenoxy]pyridine-3-carboxylic acid	158353: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined by inhibition of Urokinase-type plasminogen activator using primary assay	ic50	0.5000	uM
2-[2-methoxy-6-[[3-(trifluoromethyl)-4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]anilino]methyl]phenoxy]-5-nitrobenzoic acid	158482: Inhibitory concentration against plasminogen activator inhibitor-1 (PAI-1)	ic50	0.5000	uM
8-[4-[[6-(1-benzothiophen-2-yl)-4-hydroxy-2-oxo-1H-quinoline-3-carbonyl]amino]phenoxy]octanoic acid	225437: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by chromogenic assay.	ic50	0.5000	uM
8-[4-[[6-(1-benzothiophen-3-yl)-4-hydroxy-2-oxo-1H-quinoline-3-carbonyl]amino]phenoxy]octanoic acid	225437: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by chromogenic assay.	ic50	0.5100	uM
8-[4-[(Z)-[(5Z)-3,6-dioxo-5-[[4-(thiophene-2-carbonylamino)phenyl]methylidene]piperazin-2-ylidene]methyl]anilino]-8-oxooctanoic acid	158357: Inhibitory activity of compound against Plasminogen activator inhibitor-1	ic50	0.5200	uM
9-hydroxy-3-methoxy-4,7-dimethyl-10-[[[6-[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]-3-pyridinyl]amino]methyl]-6-oxobenzo[b][1,4]benzodioxepine-1-carboxylic acid	158353: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined by inhibition of Urokinase-type plasminogen activator using primary assay	ic50	0.5300	uM
(E)-3-[3-(3,4-difluorophenoxy)-5,6-bis[(4-phenylphenyl)methoxy]-1-benzothiophen-2-yl]-2-pyridin-4-ylprop-2-enoic acid	158355: Inhibitory activity against plasminogen activator inhibitor 1 (PAI-1) was evaluated by inhibition of tissue plasminogen activator/PAI-1 complex formation in t-PA-induced fibrin clot lysis assay	ic50	0.5900	uM
N-cyclohexyl-N-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxybenzenesulfonamide	456917: Inhibition of human recombinant PAI1 assessed as rate of AMC release after 30 mins	ic50	0.5940	uM
(3Z,6Z)-3-[[4-(3-pyridin-3-ylpropoxy)phenyl]methylidene]-6-(1,3-thiazol-2-ylmethylidene)piperazine-2,5-dione	158356: Inhibitory concentration required against Plasminogen activator inhibitor 1.	ic50	0.6000	uM
2-[2-carbamoyl-3-methyl-6-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]phenoxy]-3-hydroxy-5-methoxy-4-methylbenzoic acid	158353: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined by inhibition of Urokinase-type plasminogen activator using primary assay	ic50	0.6000	uM
8-[4-[(4-hydroxy-7-naphthalen-2-yl-2-oxo-1H-quinoline-3-carbonyl)amino]phenoxy]octanoic acid	225437: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by chromogenic assay.	ic50	0.6000	uM
(E)-3-[5-[(Z)-[3-(2-methoxyphenyl)-5-oxo-4-phenylpyrrol-2-ylidene]methyl]furan-2-yl]prop-2-enoic acid	453684: Inhibition of human PAI1	ic50	0.6500	uM
8-[4-[(4-hydroxy-6-naphthalen-2-yl-2-oxo-1H-quinoline-3-carbonyl)amino]phenoxy]octanoic acid	225437: Inhibitory activity against human plasminogen activator inhibitor-1 (PAI-1) evaluated by chromogenic assay.	ic50	0.6700	uM
(E)-3-[5-[(Z)-[4-(3,4-dimethoxyphenyl)-5-oxo-3-thiophen-2-ylpyrrol-2-ylidene]methyl]furan-2-yl]prop-2-enoic acid	453684: Inhibition of human PAI1	ic50	0.6900	uM
5-amino-2-[2-methoxy-6-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]phenoxy]benzoic acid	158353: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined by inhibition of Urokinase-type plasminogen activator using primary assay	ic50	0.7000	uM
1-[3-fluoro-6-nitro-2-[[3-(trifluoromethyl)-4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]anilino]methyl]phenyl]piperidine-4-carboxylic acid	158482: Inhibitory concentration against plasminogen activator inhibitor-1 (PAI-1)	ic50	0.7000	uM
2-[2-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]-4-nitrophenoxy]benzoic acid	158353: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined by inhibition of Urokinase-type plasminogen activator using primary assay	ic50	0.7100	uM
2-[3-fluoro-2-[[4-[[[2-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetyl]amino]methyl]anilino]methyl]phenoxy]-3-hydroxybenzoic acid	158353: Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined by inhibition of Urokinase-type plasminogen activator using primary assay	ic50	0.7100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, decreases reaction, increases expression, affects cotreatment (+1 more)	12
Benzo(a)pyrene	increases methylation, affects methylation, affects cotreatment, increases expression, decreases methylation	8
Lipopolysaccharides	increases secretion, affects expression, affects response to substance, affects reaction, affects cotreatment (+3 more)	8
Tetrachlorodibenzodioxin	increases expression, affects cotreatment, decreases expression, affects expression, decreases reaction	8
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	8
Resveratrol	affects secretion, decreases expression, affects reaction, decreases reaction, increases expression	7
Oxygen	affects reaction, decreases reaction, increases expression, increases reaction	7
Aflatoxin B1	affects expression, increases expression, affects cotreatment	7
bisphenol A	decreases reaction, affects expression, decreases expression, increases expression, increases secretion	6
Estradiol	affects cotreatment, decreases expression, increases expression	6
Cyclosporine	affects cotreatment, increases expression, decreases expression	6
Particulate Matter	affects cotreatment, decreases methylation, increases abundance, increases expression	6
Troglitazone	increases reaction, increases secretion, increases expression, affects cotreatment, decreases expression (+2 more)	5
Arsenic	decreases expression, increases expression, increases abundance, affects cotreatment	5
Copper	decreases reaction, affects binding, increases expression, decreases stability, increases oxidation (+1 more)	5
Doxorubicin	affects expression, decreases expression, increases expression, affects response to substance	5
Ethinyl Estradiol	decreases activity, affects binding, decreases expression, affects cotreatment, increases activity	5
Nickel	increases expression, increases reaction, affects binding, affects reaction, decreases stability (+1 more)	5
Rosiglitazone	decreases expression, decreases secretion, increases expression, decreases reaction, increases secretion	4
Arsenic Trioxide	increases expression, decreases expression, decreases reaction	4
Cadmium	decreases expression, increases abundance, increases expression, increases secretion	4
Paraquat	increases expression	4
lead acetate	increases expression	3
titanium dioxide	affects binding, increases secretion, affects expression, increases expression	3
arsenite	increases activity, increases expression, increases abundance	3
cobaltous chloride	increases expression, decreases reaction	3
notoginsenoside R1	decreases reaction, increases expression, increases secretion, decreases activity, affects binding	3
U 0126	decreases expression, decreases reaction, increases expression, increases secretion	3
Acetaminophen	increases expression, affects cotreatment	3
Bezafibrate	increases secretion, affects cotreatment, decreases reaction, increases expression, increases activity	3

ChEMBL screening assays

49 unique, capped per target: 48 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002153	Binding	Inhibition of human non-glycosylated PAI1 using tissue type plasminogen activator substrate by direct chromogenic assay	Mechanism of inactivation of plasminogen activator inhibitor-1 by a small molecule inhibitor. — J Biol Chem
CHEMBL766347	Functional	Plasminogen Activator Inhibitor-1 (PAI-1) activity was determined using plasma clot lysis assay	Synthesis and biological evaluation of menthol-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1). — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 2 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4GV	iPAI-026-C-K	Induced pluripotent stem cell	Female
CVCL_B8P9	Abcam HCT 116 SERPINE1 KO	Cancer cell line	Male
CVCL_B9RM	Abcam A-549 SERPINE1 KO	Cancer cell line	Male
CVCL_D1UD	Abcam U-87MG SERPINE1 KO	Cancer cell line	Male
CVCL_D8A1	Ubigene A-549 SERPINE1 KO	Cancer cell line	Male
CVCL_D9RG	Ubigene HEK293 SERPINE1 KO	Transformed cell line	Female
CVCL_E1EN	Ubigene U-87 MG SERPINE1 KO	Cancer cell line	Male
CVCL_JL78	iPAI-015-2-F	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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