PLAT

Summary

PLAT (plasminogen activator, tissue type, HGNC:9051) is a protein-coding gene on chromosome 8p11.21, encoding Tissue-type plasminogen activator (P00750). Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen.

This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5327 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombophilia, familial, due to decreased release of tissue plasminogen activator (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 107 total
• Phenotypes (HPO): 1
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000930

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9051
Approved symbol	PLAT
Name	plasminogen activator, tissue type
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104368
Ensembl biotype	protein_coding
OMIM	173370
Entrez	5327

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000220809, ENST00000352041, ENST00000429089, ENST00000429710, ENST00000519510, ENST00000520523, ENST00000521042, ENST00000521647, ENST00000521694, ENST00000522812, ENST00000524009, ENST00000524261, ENST00000677722, ENST00000678083, ENST00000678676, ENST00000679151, ENST00000679300, ENST00000884022, ENST00000884023, ENST00000884024, ENST00000884025, ENST00000915840, ENST00000944404, ENST00000944405

RefSeq mRNA: 3 — MANE Select: NM_000930 NM_000930, NM_001319189, NM_033011

CCDS: CCDS6126, CCDS6127, CCDS83291

Canonical transcript exons

ENST00000220809 — 14 exons

Exon	Start	End
ENSE00000692400	42182719	42182890
ENSE00000692402	42185081	42185172
ENSE00000692406	42187906	42188016
ENSE00001128022	42187398	42187572
ENSE00001605389	42180242	42180378
ENSE00001617965	42191372	42191414
ENSE00001727998	42188934	42189071
ENSE00001793485	42179926	42180066
ENSE00002137331	42207494	42207565
ENSE00002181240	42193114	42193211
ENSE00003497155	42180490	42180685
ENSE00003633367	42181937	42182022
ENSE00003651450	42178897	42179063
ENSE00003894645	42174718	42176151

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.8258 / max 3422.5622, expressed in 1317 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92896	41.3643	1236
92897	17.6812	951
92889	0.1639	68
92888	0.1332	53
92891	0.1088	44
92893	0.0912	35
92894	0.0864	29
92895	0.0858	34
92892	0.0626	30
92890	0.0484	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.23	gold quality
pancreatic ductal cell	CL:0002079	98.90	gold quality
urethra	UBERON:0000057	98.34	gold quality
vena cava	UBERON:0004087	98.17	gold quality
mucosa of urinary bladder	UBERON:0001259	98.05	gold quality
metanephros cortex	UBERON:0010533	97.46	gold quality
mammary duct	UBERON:0001765	97.36	gold quality
epithelium of mammary gland	UBERON:0003244	96.49	gold quality
pylorus	UBERON:0001166	96.42	gold quality
gall bladder	UBERON:0002110	96.36	gold quality
metanephros	UBERON:0000081	96.05	gold quality
urinary bladder	UBERON:0001255	96.04	gold quality
left uterine tube	UBERON:0001303	96.01	gold quality
cardia of stomach	UBERON:0001162	95.97	gold quality
renal medulla	UBERON:0000362	95.79	gold quality
pericardium	UBERON:0002407	95.56	gold quality
colonic epithelium	UBERON:0000397	95.50	gold quality
metanephric glomerulus	UBERON:0004736	94.78	gold quality
seminal vesicle	UBERON:0000998	94.72	gold quality
epithelial cell of pancreas	CL:0000083	94.71	gold quality
caecum	UBERON:0001153	94.59	gold quality
trigeminal ganglion	UBERON:0001675	94.19	gold quality
renal glomerulus	UBERON:0000074	94.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.87	gold quality
thoracic mammary gland	UBERON:0005200	93.70	gold quality
olfactory bulb	UBERON:0002264	93.68	gold quality
rectum	UBERON:0001052	93.67	gold quality
adult mammalian kidney	UBERON:0000082	93.65	gold quality
mammary gland	UBERON:0001911	93.63	gold quality
vermiform appendix	UBERON:0001154	93.56	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	2624.80
E-GEOD-124858	yes	1474.20
E-CURD-114	yes	518.38
E-MTAB-10287	yes	110.05
E-GEOD-135922	yes	36.13
E-CURD-119	yes	24.92
E-CURD-112	yes	11.75
E-MTAB-5061	yes	11.25
E-MTAB-9067	yes	7.15
E-GEOD-83139	yes	6.69
E-ENAD-20	no	1002.02
E-MTAB-10137	no	740.03
E-MTAB-10290	no	138.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF2, ATF4, CREB1, CREM, DBP, DNMT1, EGR1, FOS, HIF1A, HOXB2, JUN, JUND, KLF5, MSC, NF1, RARA, RARB, RXRA, SP1, SP3, TCF3, TP53

miRNA regulators (miRDB)

90 targeting PLAT, 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-340-5P	100.00	72.50	4437
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• Steps and dynamics of disintegration and reorganization of fibrin networks during tissue-type plasminogen activator-induced clot lysis. (PMID:11734662)
• mean transit time, the net quantitative turnover rate, and the sites of synthesis and catabolism (PMID:11734664)
• PAI-1/ tPA imbalance is associated with myocardial infarction at young age in Japanese men. (PMID:11816707)
• Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction. Genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information. (PMID:11848437)
• TPA & urokinase progressed to maximum levels in late pregnancy, but decreased in labor, favoring a coagulation state despite elevated D-dimer levels suggesting enhanced fibrinolysis. (PMID:11858184)
• vWF and tPAag but not thrombomodulin in the present population are independent markers of atherosclerosis. (PMID:11864703)
• Arsenite caused a decrease of t-PA mRNA level and a rise of both PAI-1 mRNA level and activity in microvascular endothelial cells, but not umbilical vein endothelial cells, suggesting a role in Blackfoot disease, a peripheral vascular occlusive disease. (PMID:11864708)
• In a study of the differential role of UPA and TPA as inducers of fibronectin mRNA, TPA led to an increase of FN mRNA expression in early G1, led to FN assembly in the ECM, induced dimeric FN (PMID:11928812)
• Tissue-type plasminogen activator is stored in Weibel-Palade bodies in endothelial cells (PMID:11986218)
• role of the plasminogen activator and matrix metalloproteinase systems in matrix remodeling in the ovary (PMID:11988309)
• Tissue plasminogen activator as a key effector in neurobiology and neuropathology. Review. (PMID:12023848)
• tPA is induced by oncostatin M in lung tumor cells (PMID:12090757)
• interactions between the fibrinolytic and renin-angiotensin systems play an important role in the genetic architecture of plasma t-PA (PMID:12123488)
• 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)
• The interactions between NSP and t-PA were distinct from those between plasmin and NSP, suggesting that the physiologic effect of t-PA-NSP interactions may be more complex than previously thought. (PMID:12228252)
• Cloning and identification of human tissue-type plasminogen activator gene. (PMID:12390834)
• Calcium-regulated secretion of tissue-type plasminogen activator in vascular endothelial cells. (PMID:12445472)
• amino acids critical for tPA-annexin A2 interaction (PMID:12468550)
• hypoxia decreased tissue plasminogen activator in both normal peritoneal fibroblasts and adhesion fibroblasts (PMID:12524082)
• reactive hyperemia stimulates t-PA release; that relationship is altered when endothelium is dysfunctional. Release of t-PA is independent of adenosine or products of muscarinic stimulation and may be related to the activity of the kininogen/kinin system. (PMID:12544724)
• Recombinant tissue plasminogen activator (alteplase)is effective for restoration of function to occluded central venous catheters in a pediatric population with thrombosis (PMID:12544772)
• The possible influence of the Alu-repeat polymorphism on t-PA release was evaluated after a venous occlusion test in venous occlusion. (PMID:12643326)
• Tetranectin binds to this protein and hepatocyte growth factor. (PMID:12694198)
• results show that the NH(2)-terminal part of PrP(c) spanning amino acids 23-110 (PrP23-110) together with low molecular weight heparin stimulates t-PA mediated plasminogen activation in vitro (PMID:12719777)
• tPA and plasma kallikrein-mediated uPA activation and tPA release contribute to endogenous fibrinolytic or thrombolytic mechanisms. (PMID:12719778)
• In normal conditions and in the presence of IL-1beta, cathepsin B is involved in the activation of plasminogen activator in osteoblasts. (PMID:12726991)
• These results suggest that the recombinant kringle domain of tissue-type plasminogen activator (t-PA) is a selective inhibitor of endothelial cell growth and identifies this molecule as a novel anti-angiogenic agent. (PMID:12727218)
• Dengue virus infection significanlty increased production of tissue plasminogen activator (tPA) in primary isolated endothelial cells, human umbilical cord veins cells, and a human microvascular endothelial cell line (PMID:12794725)
• evidence to support the hypothesis that p63 is the functional tPA binding site on VSMC (PMID:12913003)
• TAFIa inhibited lysis of model thrombi and plasma clots by uPA, scuPA and tPA, which could be partially overcome by plasminogen, consistent with TAFIa exerting its effect through modifying the binding of plasminogen and tPA to fibrin. (PMID:12941043)
• the catalytic domain of tissue-type plasminogen activator is distorted by plasminogen activator inhibitor-1, leading to the formation of stable serpin-proteinase complexes (PMID:14500731)
• High concentration of plasma tPA was an independent marker for poor prognosis in patients with ovarian cancer. (PMID:14529669)
• in response to T beta 4 stimulation, AP-1 activity increases to enhance PAI-1 transcription through its unique AP-1-like element at -59 to -52 in the PAI-1 promoter. (PMID:14592829)
• A coconut oil-based diet lowers postprandial t-PA antigen concentration. (PMID:14608053)
• anti-tPA antibodies specifically interacting with the catalytic domain of tPA can be found in patients with antiphospholipid syndrome, representing a possible cause of hypofibrinolysis. (PMID:14630788)
• t-PA antigen concentration (P =.001), fibrinogen and time on dialysis prior to transplantation (P <.05) were positive independent predictors of carotid intima media thickness in kidney transplantation. (PMID:14697941)
• t-PA mediated plasminogen activation involves prion-protein fragment PrP23-110 lysine clusters (PMID:14983221)
• Adenosine deaminase and Plasminogen bind simultaneously to CD26 in a ternary complex that stimulates the Pg activation by its physiologic activators. (PMID:15016824)
• Neuronal depolarization induces a release of t-PA. This release of t-PA is sensitive to exocytosis inhibition and calcium chelation. Released t-PA modulates NMDA receptor signaling. (PMID:15080889)
• There is a basal net release of t-PA across the human cerebral vascular bed and sympathoadrenal activation induces a local regulated release of t-PA. (PMID:15116264)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plat	ENSDARG00000062707
mus_musculus	Plat	ENSMUSG00000031538
rattus_norvegicus	Plat	ENSRNOG00000019018

Paralogs (14): PRSS33 (ENSG00000103355), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022), PRSS50 (ENSG00000283706)

Protein

Protein identifiers

Tissue-type plasminogen activator — P00750 (reviewed: P00750)

All UniProt accessions (10): P00750, A0A7I2V268, A0A7I2V6D6, A0A7I2YQ93, B4DN26, B4DNJ1, E5RGA1, E5RHG4, E7ESF4, H0YBH9

UniProt curated annotations — full annotation on UniProt →

Function. Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy.

Subunit / interactions. Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between 100-fold and 1000-fold, due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is followed by internalization and degradation. Interacts with SERPINE1. In complex with SERPINE1, interacts with SORL1. Interacts with apyrase from Anopheles gambiae saliva; the interaction results in PLAT activation probably via an allosteric activation mechanism.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.

Post-translational modifications. The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa. Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the presence of fibrin. N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor. Characterization of O-linked glycan was studied in Bowes melanoma cell line.

Disease relevance. Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism.

Activity regulation. Inhibited by SERPINA5. Inhibited by SERPINE1.

Domain organisation. Both FN1 and one of the kringle domains are required for binding to fibrin. Both FN1 and EGF-like domains are important for binding to LRP1. The FN1 domain mediates binding to annexin A2. The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase S1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P00750-1	1, Long	yes
P00750-2	2, Short
P00750-3	3
P00750-4	4, Neonatal

RefSeq proteins (3): NP_000921, NP_001306118, NP_127509 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000083	Fibronectin_type1	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR026280	Tissue_plasm_act	Family
IPR033116	TRYPSIN_SER	Active_site
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR050127	Serine_Proteases_S1	Family

Pfam: PF00008, PF00039, PF00051, PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.68 — t-Plasminogen activator (BRENDA: 13 organisms, 167 substrates, 120 inhibitors, 209 Km, 185 kcat entries)

Substrate kinetics (BRENDA)

99 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
LYS-PLASMINOGEN	—	30
SPECTROZYME TPA	0.4–4.6	11
D-ILE-PRO-ARG-P-NITROANILIDE	0.0001–0.694	8
PLASMINOGEN	—	8
BOC-(P-F)-FPRANSNH-C2H5	0.0004–0.071	5
BOC-D-VGRANSNH-C4H9	0.0007–0.14	5
(P-F)-FPRANSNH-C2H5	0.0004–0.39	4
BOC-D-FVRANSNH-C2H5	0.0027–0.091	4
BOC-D-LGRANSNH-C6H11	0.0004–0.023	4
BOC-D-LPRANSNH-C3H7	0.0006–0.066	4
BOC-D-LSRANSNH-C3H7	0.0006–0.36	4
D-FVRANSNH-C2H5	0.0011–0.016	4
D-LPRANSNH-C3H7	0.0003–0.098	4
D-LSRANSNH-C3H7	0.0012–0.069	4
D-VPRANSNH-C4H9	0.0003–0.11	4

UniProt features (104 total): strand 39, disulfide bond 17, helix 8, sequence conflict 6, domain 5, splice variant 5, site 4, glycosylation site 4, sequence variant 4, active site 3, chain 3, propeptide 2, turn 2, signal peptide 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
1RTF	X-RAY DIFFRACTION	2.3
1PML	X-RAY DIFFRACTION	2.38
1TPK	X-RAY DIFFRACTION	2.4
1A5H	X-RAY DIFFRACTION	2.9
5BRR	X-RAY DIFFRACTION	3.16
1BDA	X-RAY DIFFRACTION	3.35
5ZLZ	X-RAY DIFFRACTION	3.58
1PK2	SOLUTION NMR
1TPG	SOLUTION NMR
1TPM	SOLUTION NMR
1TPN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00750-F1	81.28	0.36

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 (7): 357 (charge relay system); 406 (charge relay system); 513 (charge relay system); 102 (important for binding to lrp1); 253 (not glycosylated); 464 (important for single-chain activity); 512 (important for single-chain activity)

Disulfide bonds (17): 41–71, 69–78, 86–97, 91–108, 110–119, 127–208, 148–190, 179–203, 215–296, 236–278, 267–291, 299–430, 342–358, 350–419, 444–519, 476–492, 509–537

Glycosylation sites (4): 96, 152, 219, 483

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-186797	Signaling by PDGF
R-HSA-75205	Dissolution of Fibrin Clot

MSigDB gene sets: 399 (showing top): MODULE_172, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_SINGLE_FERTILIZATION, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOCC_CELL_SURFACE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING

GO Biological Process (15): response to hypoxia (GO:0001666), proteolysis (GO:0006508), blood coagulation (GO:0007596), negative regulation of plasminogen activation (GO:0010757), smooth muscle cell migration (GO:0014909), plasminogen activation (GO:0031639), protein modification process (GO:0036211), fibrinolysis (GO:0042730), negative regulation of proteolysis (GO:0045861), platelet-derived growth factor receptor signaling pathway (GO:0048008), negative regulation of fibrinolysis (GO:0051918), prevention of polyspermy (GO:0060468), trans-synaptic signaling by BDNF, modulating synaptic transmission (GO:0099183), SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition (GO:0006617), zymogen activation (GO:0031638)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), phosphoprotein binding (GO:0051219), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cell surface (GO:0009986), secretory granule (GO:0030141), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), serine protease inhibitor complex (GO:0097180), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), signal recognition particle, endoplasmic reticulum targeting (GO:0005786)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein metabolic process	2
protein binding	2
synapse	2
response to stress	1
response to decreased oxygen levels	1
hemostasis	1
wound healing	1
coagulation	1
regulation of plasminogen activation	1
negative regulation of protein processing	1
plasminogen activation	1
muscle cell migration	1
zymogen activation	1
macromolecule modification	1
negative regulation of blood coagulation	1
proteolysis	1
regulation of proteolysis	1
negative regulation of protein metabolic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
fibrinolysis	1
negative regulation of biological process	1
regulation of fibrinolysis	1
egg activation	1
negative regulation of fertilization	1
trans-synaptic signaling by BDNF	1
trans-synaptic signaling, modulating synaptic transmission	1
SRP-dependent cotranslational protein targeting to membrane	1
protein-containing complex assembly	1
protein processing	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1

Protein interactions and networks

STRING

2916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAT	SERPINE1	P05121	999
PLAT	ANXA2	P07355	994
PLAT	PLG	P00747	989
PLAT	S100A10	P08206	979
PLAT	LRP1	Q07954	974
PLAT	VWF	P04275	931
PLAT	F3	P13726	922
PLAT	SERPINC1	P01008	915
PLAT	CPB2	Q96IY4	912
PLAT	THBD	P07204	904
PLAT	MMP9	P14780	892
PLAT	SERPINF2	P08697	886
PLAT	SERPINB2	P05120	880
PLAT	SERPINI1	Q99574	829
PLAT	PLAUR	Q03405	826

IntAct

36 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
	PLOD2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
IFNA14	IFIT3	psi-mi:“MI:0914”(association)	0.530
IGFBP1	SUSD5	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
SERPING1	PLAT	psi-mi:“MI:0914”(association)	0.500
SERPING1	PLAT	psi-mi:“MI:0915”(physical association)	0.500
SERPINE1	PLAT	psi-mi:“MI:0407”(direct interaction)	0.440
PLAT	PLAT	psi-mi:“MI:0407”(direct interaction)	0.440
PLAT	Plgrkt	psi-mi:“MI:0915”(physical association)	0.400
rep	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
IGFL3	CBX4	psi-mi:“MI:0914”(association)	0.350
CCL3L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
FGL1	DNM1L	psi-mi:“MI:0914”(association)	0.350
SLURP1	MANBA	psi-mi:“MI:0914”(association)	0.350
TMEM25	NME4	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
SERPINB2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
SERPINF2	RNASEH1	psi-mi:“MI:0914”(association)	0.350
MSMB	ADAM11	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Reconstituted Complex), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS), PLAT (Affinity Capture-MS)

ESM2 similar proteins: A0A182C2Z2, A0A1S4GMJ4, A6MFK8, B5G6G5, O15393, O60235, O70244, O96900, P00750, P05156, P11214, P19637, P25723, P29598, P79953, P81428, P82807, P83370, P86091, P97435, P98072, P98073, P98074, P98119, P98121, Q05589, Q14C59, Q17800, Q20176, Q4QXT9, Q58L93, Q58L94, Q5QSK2, Q5R5A4, Q5R8J0, Q61129, Q66TN7, Q6DIV5, Q6IE14, Q6ZMR5

Diamond homologs: A0A126GUP6, A0A1S4H5M5, A0A1S4H5S2, A0A6I8TBG6, A0A6J1W8N1, A6MFK8, A6NIE9, B7YZU2, C0HKA2, C0HKA3, C0HKA4, F5HKX0, O97366, P00745, P00749, P00750, P00760, P00761, P00762, P00763, P00764, P00766, P03952, P04070, P06868, P06872, P07146, P08426, P11214, P14272, P15944, P19637, P20231, P21845, P27435, P31394, P33587, P35030, P35033, P40313

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ATF2	“up-regulates quantity by expression”	PLAT	“transcriptional regulation”
CREB1	“down-regulates quantity by repression”	PLAT	“transcriptional regulation”
PLAT	“up-regulates activity”	PLG	binding
PLG	“up-regulates activity”	PLAT	cleavage
Fibrin	up-regulates	PLAT

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	20
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1891 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42179062:CA:C	acceptor_gain	1.0000
8:42179064:C:CC	acceptor_gain	1.0000
8:42179913:T:TA	donor_gain	1.0000
8:42179924:A:AC	donor_gain	1.0000
8:42179924:ACAGG:A	donor_gain	1.0000
8:42179925:C:CC	donor_gain	1.0000
8:42179925:CAGG:C	donor_gain	1.0000
8:42179925:CAGGC:C	donor_gain	1.0000
8:42179939:G:A	donor_gain	1.0000
8:42180062:CAGCG:C	acceptor_gain	1.0000
8:42180063:AGCG:A	acceptor_gain	1.0000
8:42180064:GCG:G	acceptor_gain	1.0000
8:42180065:C:CT	acceptor_gain	1.0000
8:42180065:CG:C	acceptor_gain	1.0000
8:42180067:C:CC	acceptor_gain	1.0000
8:42180068:T:C	acceptor_loss	1.0000
8:42180236:TCTTA:T	donor_loss	1.0000
8:42180237:CTTAC:C	donor_loss	1.0000
8:42180238:TTA:T	donor_loss	1.0000
8:42180239:TACCA:T	donor_loss	1.0000
8:42180240:A:AC	donor_gain	1.0000
8:42180240:A:C	donor_loss	1.0000
8:42180241:C:CA	donor_loss	1.0000
8:42180241:C:CC	donor_gain	1.0000
8:42180241:CCA:C	donor_gain	1.0000
8:42180274:T:TA	donor_gain	1.0000
8:42180376:AACCT:A	acceptor_loss	1.0000
8:42180377:ACCTG:A	acceptor_loss	1.0000
8:42180379:C:CC	acceptor_gain	1.0000
8:42180379:CTGGT:C	acceptor_loss	1.0000

AlphaMissense

3688 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:42178901:C:G	C509S	0.998
8:42178902:A:T	C509S	0.998
8:42178952:C:G	C492S	0.997
8:42178953:A:T	C492S	0.997
8:42180603:C:A	W324C	0.997
8:42180603:C:G	W324C	0.997
8:42187484:C:A	W151C	0.997
8:42187484:C:G	W151C	0.997
8:42176017:C:A	W555C	0.996
8:42176017:C:G	W555C	0.996
8:42176072:C:G	C537S	0.996
8:42176073:A:T	C537S	0.996
8:42179000:C:G	C476S	0.996
8:42179001:A:T	C476S	0.996
8:42180605:A:G	W324R	0.996
8:42180605:A:T	W324R	0.996
8:42182805:C:A	W239C	0.996
8:42182805:C:G	W239C	0.996
8:42176086:G:C	S532R	0.995
8:42176086:G:T	S532R	0.995
8:42176088:T:G	S532R	0.995
8:42176132:A:G	L517P	0.995
8:42176147:T:A	D512V	0.995
8:42178901:C:T	C509Y	0.995
8:42180063:A:G	L409P	0.995
8:42180501:G:C	C358W	0.995
8:42176083:C:A	W533C	0.994
8:42176083:C:G	W533C	0.994
8:42176147:T:G	D512A	0.994
8:42178953:A:G	C492R	0.994

dbSNP variants (sampled 300 via entrez): RS1000012336 (8:42192610 T>C), RS1000068928 (8:42199378 A>G), RS1000089465 (8:42197218 A>G), RS1000167980 (8:42208710 C>G,T), RS1000235981 (8:42180913 T>C), RS1000294694 (8:42193008 C>T), RS1000526411 (8:42199067 T>G), RS1000628624 (8:42194563 G>A), RS1000639805 (8:42207645 G>A), RS1000708281 (8:42209007 G>A,T), RS1000786171 (8:42180067 C>CT), RS1000799625 (8:42187695 C>A,G), RS1000864009 (8:42186585 T>G), RS1000900649 (8:42180237 C>T), RS1000959083 (8:42182466 A>C)

Disease associations

OMIM: gene MIM:173370 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombophilia, familial, due to decreased release of tissue plasminogen activator	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
thrombophilia, familial, due to decreased release of tissue plasminogen activator	Disputed	AD

Mondo (4): pulmonary embolism (MONDO:0005279), thrombocytopenia (MONDO:0002049), hereditary angioedema with normal C1Inh (MONDO:0100567), thrombophilia, familial, due to decreased release of tissue plasminogen activator (MONDO:0012872)

Orphanet (1): Hereditary angioedema with normal C1Inh (Orphanet:528647)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002204	Pulmonary embolism

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002374_1	Plasma plasminogen activator levels	2.000000e-08
GCST005752_19	Systemic lupus erythematosus	3.000000e-08
GCST006585_4	Blood protein levels	1.000000e-12

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D011655	Pulmonary Embolism	C08.381.746; C14.907.355.350.700
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C567341	Thrombophilia, Familial, Due To Decreased Release Of Tissue Plasminogen Activator (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1873 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 50,191 (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
CHEMBL1166	ARGATROBAN	4	231
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL877	TRANEXAMIC ACID	4	27,519
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL48361	DABIGATRAN	3	13,443
CHEMBL87563	GABEXATE	3	2,031
CHEMBL1095032	LETAXABAN	2	375
CHEMBL273196	EFEGATRAN	2	1,037

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
Dup-714	Inhibition	8.24	pKi

Binding affinities (BindingDB)

534 measured of 555 human assays (557 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R)-N-[(3-aminobenzene)sulfonyl]-2-[(4-carbamimidoyl-3-hydroxyphenyl)amino]-2-(3,5-diethoxy-2-fluorophenyl)acetamide	KI	0.35 nM
CDE-082	KD	5.3 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
2-methyl-3-[3-[2-[(2-methylpropan-2-yl)oxy]ethyl]-1,2,4-oxadiazol-5-yl]-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	6 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
Tannic Acid, A	IC50	7 nM
3-(2-methylbutanoyl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	8 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(cyclopropanecarbonyl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	8 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(2-methyl-1,3-thiazol-5-yl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	8.2 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-piperidin-4-yl-3-[5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	8.7 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(piperidine-1-carbonyl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	9 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(4-cyclohexyl-1,3-thiazol-2-yl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	9 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[3-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-5-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	9.7 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[5-(2-phenylethyl)-1,3,4-oxadiazol-2-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	10 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[5-(2-methylcyclopentyl)-1,2,4-oxadiazol-3-yl]-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	10 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2-methyl-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	10 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[3-[(4-hydroxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-2-methyl-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	10 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
CDE-066	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
ethyl 5-oxo-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxylate	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
5-(5-oxo-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-3-yl)thiophene-3-carbonitrile	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[5-[(3-chlorophenyl)methyl]-1,3,4-oxadiazol-2-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
2-methyl-3-[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(4-ethyl-1,3-thiazol-2-yl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-2-methyl-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
cyclobutyl 2-methyl-5-oxo-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxylate	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-piperidin-4-yl-3-(1,2-thiazol-5-yl)-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(cyclopentanecarbonyl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	11 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-piperidin-4-yl-3-(3-propyl-1,2,4-oxadiazol-5-yl)-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	12 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-(2-methylpiperidin-4-yl)-5-oxo-4H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	IC50	12 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(benzenesulfonyl)-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	12 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[5-[4-methyl-2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	12 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(3,3-difluoroazetidine-1-carbonyl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	12 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]-2-methyl-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	12 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
N-benzyl-5-oxo-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidine-3-carboxamide	IC50	13 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-piperidin-4-yl-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	13 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
4-(5-oxo-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-3-yl)benzonitrile	IC50	13 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(3-methoxyphenyl)-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	13 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(5-methyl-4-phenyl-1,3-thiazol-2-yl)-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	13 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
N-(2-methylpropyl)-5-oxo-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(morpholine-4-carbonyl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-chloro-7-(2-methylpiperidin-4-yl)-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(3-chlorophenyl)-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-piperidin-4-yl-3-[3-(trifluoromethoxy)phenyl]-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
7-piperidin-4-yl-3-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[5-[(2-chlorophenyl)methyl]-1,3,4-oxadiazol-2-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
methyl 5-oxo-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxylate	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(5-cyclopentyl-1,2,4-oxadiazol-3-yl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-[5-[(3-fluoro-4-methoxyphenyl)methyl]-1,3,4-oxadiazol-2-yl]-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	14 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
benzyl 5-oxo-7-piperidin-4-yl-2,3,3a,4-tetrahydro-1H-pyrazolo[1,5-a]pyrimidine-3-carboxylate	IC50	15 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
N-ethyl-5-oxo-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide	IC50	15 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use
3-(3-methyl-1,2,4-oxadiazol-5-yl)-7-piperidin-4-yl-4H-pyrazolo[1,5-a]pyrimidin-5-one	IC50	15 nM	US-10118930: Piperidinylpyrazolopyrimidinones and their use

ChEMBL bioactivities

729 potent at pChembl≥5 of 864 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.54	Ki	0.29	nM	CHEMBL439678
9.15	IC50	0.7	nM	CHEMBL105819
8.52	Ki	3	nM	CHEMBL92615
8.24	Ki	5.7	nM	CHEMBL290376
8.22	IC50	6	nM	CHEMBL5901486
8.22	Ki	6	nM	CHEMBL418965
8.22	Ki	6	nM	CHEMBL94952
8.10	IC50	8	nM	CHEMBL4457757
8.10	IC50	8	nM	CHEMBL4460436
8.09	IC50	8.2	nM	CHEMBL5964796
8.06	IC50	8.7	nM	CHEMBL5905253
8.05	IC50	9	nM	CHEMBL5901046
8.05	IC50	9	nM	CHEMBL5962457
8.01	IC50	9.7	nM	CHEMBL5787485
8.00	IC50	10	nM	CHEMBL5862509
8.00	IC50	10	nM	CHEMBL5757367
8.00	IC50	10	nM	CHEMBL5985991
8.00	IC50	10	nM	CHEMBL5831764
7.96	IC50	11	nM	CHEMBL5946146
7.96	IC50	11	nM	CHEMBL5747109
7.96	IC50	11	nM	CHEMBL5856374
7.96	IC50	11	nM	CHEMBL5903246
7.96	IC50	11	nM	CHEMBL5758338
7.96	IC50	11	nM	CHEMBL6007660
7.96	IC50	11	nM	CHEMBL5940635
7.96	IC50	11	nM	CHEMBL5984212
7.96	IC50	11	nM	CHEMBL5874921
7.92	IC50	12	nM	CHEMBL5869606
7.92	IC50	12	nM	CHEMBL5816419
7.92	IC50	12	nM	CHEMBL5821304
7.92	IC50	12	nM	CHEMBL5858525
7.92	IC50	12	nM	CHEMBL6060319
7.92	IC50	12	nM	CHEMBL5879772
7.89	IC50	13	nM	CHEMBL6039037
7.89	IC50	13	nM	CHEMBL5950561
7.89	IC50	13	nM	CHEMBL6041995
7.89	IC50	13	nM	CHEMBL5948508
7.89	IC50	13	nM	CHEMBL6014715
7.85	IC50	14	nM	CHEMBL5751381
7.85	IC50	14	nM	CHEMBL6062932
7.85	IC50	14	nM	CHEMBL5998861
7.85	IC50	14	nM	CHEMBL5967117
7.85	IC50	14	nM	CHEMBL5896322
7.85	IC50	14	nM	CHEMBL6003517
7.85	IC50	14	nM	CHEMBL6016504
7.85	IC50	14	nM	CHEMBL5880017
7.85	IC50	14	nM	CHEMBL5826722
7.85	IC50	14	nM	CHEMBL5792440
7.85	IC50	14	nM	CHEMBL5799725
7.82	IC50	15	nM	CHEMBL5896355

PubChem BioAssay actives

254 with measured affinity, of 1089 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(3-chlorophenyl)methyl]-N-(2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.0003	uM
(2S)-2-[[(2S)-2-[4-(diaminomethylideneamino)butanoylamino]-3-(4-nitrophenyl)propanoyl]-methylamino]-3-hydroxy-N-[(1R)-1-phenylethyl]butanamide	225436: Concentration required to inhibit tissue-type plasminogen activator (t-PA) was determined	ic50	0.0007	uM
(20S)-20-benzyl-8,25-dichloro-18-methyl-12-oxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0030	uM
(20S)-20-benzyl-8,25-dichloro-12-oxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0060	uM
(14Z,21S)-21-benzyl-8,26-dichloro-12,17-dioxa-1,4,19,22,24-pentazatricyclo[21.3.1.06,11]heptacosa-6(11),7,9,14,23,25-hexaene-3,18,27-trione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0060	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	0.0080	uM
[(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.”	ic50	0.0120	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.”	ic50	0.0180	uM
2-(2-hydroxy-5-nitro-3-phenylphenyl)-1H-indole-5-carboximidamide	228025: Inhibition of Human Serine Protease tissue type Plasminogen Activator (t-PA).	ki	0.0190	uM
(19S)-19-benzyl-8,24-dichloro-12-oxa-1,4,17,20,22-pentazatricyclo[19.3.1.06,11]pentacosa-6(11),7,9,21,23-pentaene-3,25-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0200	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.”	ic50	0.0280	uM
(2R)-N-[2-[[(2S)-1-(1,3-benzoxazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]-5-(diaminomethylideneamino)-2-(2-phenylethylsulfonylamino)pentanamide	321207: Inhibition of tPA	ic50	0.0290	uM
(2S)-N-[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	210922: Concentration required to inhibit Tissue-type plasminogen activator (t-PA) was determined	ic50	0.0340	uM
(2E,7E)-2,7-bis[[4-(diaminomethyl)phenyl]methylidene]cycloheptan-1-one	210925: Inhibitory activity against human tissue-type plasminogen activator expressed as dissociation constant	ki	0.0350	uM
2-(2-hydroxy-3-phenoxyphenyl)-1H-indole-5-carboximidamide	210928: Inhibition of tissue-type plasminogen activator	ki	0.0350	uM
2-(2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.0350	uM
2-[(2R)-2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.0500	uM
ethyl 2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetate	254331: Inhibitory constant against tissue plasminogen activator	ki	0.0670	uM
2-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264687: Inhibition of tPA	ic50	0.0700	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.”	ic50	0.0860	uM
2-[2-[[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]methoxy]phenyl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.0900	uM
2-[2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]ethoxy]benzoic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.0900	uM
(3S,6R)-6-amino-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-benzyl-2,3,5,7,8,8a-hexahydro-1H-indolizine-3-carboxamide	210915: Inhibitory concentration against Tissue type plasminogen activator	ic50	0.0930	uM
2-(5-bromo-2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.0940	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]ethanol	254331: Inhibitory constant against tissue plasminogen activator	ki	0.0960	uM
N-[2-(1-benzylpiperidin-2-yl)ethyl]-2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.1000	uM
2-[2-[[5-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-3,3-dimethyl-2H-1-benzofuran-7-yl]methoxy]phenyl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.1000	uM
(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]-N-[(2S)-1-chloro-5-(diaminomethylideneamino)pentan-2-yl]pyrrolidine-2-carboxamide	210920: Compound was evaluated for the inhibition of Tissue type plasminogen activator (tissue plasminogen activator)	ki	0.1060	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetic acid	254331: Inhibitory constant against tissue plasminogen activator	ki	0.1100	uM
6-chloro-2-(2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	225425: The compound was tested for inhibition of human plasmin	ki	0.1100	uM
2-(2-hydroxy-5-methyl-3-phenylphenyl)-1H-indole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.1100	uM
2-[[(2S)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	766526: Inhibition of human t-PA	ki	0.1130	uM
2-[[4-[(6Z)-6-(iodomethylidene)-2-oxooxan-3-yl]phenyl]methyl]guanidine	210723: Compound was tested for its binding affinity against the enzyme Tissue plasminogen activator	ki	0.1200	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoylfuran-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264687: Inhibition of tPA	ic50	0.1250	uM
6-carbamimidoyl-4-(oxolan-3-yl)-N-(3-propan-2-yloxyphenyl)naphthalene-2-carboxamide	210919: Binding affinity towards tissue type plasminogen activator	ki	0.1300	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.1400	uM
(20S)-20-benzyl-8,25-dichloro-12,15-dioxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.1500	uM
N-[5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-2-(2-oxo-4-quinolin-8-ylsulfonylpiperazin-1-yl)acetamide	210758: Inhibitory activity against tissue plasminogen activator (tissue plasminogen activator)	ic50	0.1500	uM
2-(5-chloro-2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.1600	uM
2-(2-hydroxy-3-phenylphenyl)-3H-benzimidazole-5-carboximidamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.1600	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoyl-1,3-thiazol-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264687: Inhibition of tPA	ic50	0.1730	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.”	ic50	0.1740	uM
6-carbamimidoyl-4-(furan-3-yl)-N-phenylnaphthalene-2-carboxamide	238775: Binding affinity value against Tissue plasminogen activator	ki	0.1760	uM
2-[2-[[5-[(4R)-4-amino-3,4-dihydro-2H-chromen-6-yl]-3,3-dimethyl-2H-1-benzofuran-7-yl]methoxy]phenyl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.1900	uM
N-(4-carbamimidoylphenyl)-2-hydroxy-3-iodo-5-methylbenzamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.1900	uM
2-(2-hydroxy-3-phenylphenyl)-6-methyl-1H-indole-5-carboximidamide	225425: The compound was tested for inhibition of human plasmin	ki	0.2100	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2,2-difluoro-2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.2400	uM
1-[(2S)-2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]-2-hydroxyethyl]indole-7-carboxylic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.2500	uM
2-(5-chloro-2-hydroxy-3-phenylphenyl)-3H-benzimidazole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.2800	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	270829: Inhibition of recombinant tPA	ic50	0.2800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases secretion, affects expression, affects cotreatment, increases expression (+1 more)	10
Tretinoin	increases expression, decreases expression	8
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	6
Valproic Acid	affects cotreatment, increases expression	5
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
Dexamethasone	decreases activity, decreases expression, affects cotreatment	3
Ethinyl Estradiol	decreases expression, increases activity, affects cotreatment	3
Nicotine	affects expression, affects cotreatment, increases expression	3
Quercetin	increases reaction, increases expression, increases secretion, decreases expression, affects binding (+1 more)	3
Levonorgestrel	affects cotreatment, decreases expression, increases activity	3
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	decreases expression, decreases reaction, affects cotreatment, affects expression	2
arsenite	decreases activity, decreases secretion, affects reaction, decreases expression, decreases reaction	2
geranylgeraniol	decreases reaction, increases expression	2
nickel sulfate	increases expression	2
notoginsenoside R1	increases expression, affects binding	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	decreases reaction, increases expression, increases degradation, increases reaction, decreases expression (+1 more)	2
Arsenic Trioxide	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression	2
Blood Glucose	affects cotreatment, decreases reaction, increases expression, increases degradation, increases reaction	2
Cadmium	decreases activity, increases expression	2
Dactinomycin	affects cotreatment, increases expression, increases secretion, decreases reaction	2
Mevalonic Acid	increases expression, decreases reaction	2
Oxygen	affects cotreatment, decreases reaction, increases expression, increases degradation, increases reaction	2
Smoke	decreases expression, increases abundance, increases expression	2

ChEMBL screening assays

249 unique, capped per target: 243 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008042	Binding	Inhibition of recombinant tissue plasminogen activator	Design, structure-activity relationships, X-ray crystal structure, and energetic contributions of a critical P1 pharmacophore: 3-chloroindole-7-yl-based factor Xa inhibitors. — J Med Chem
CHEMBL4621405	ADMET	Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach. — J Med Chem
CHEMBL6108564	Functional	Inhibition of recombinant human tissue plasminogen activator (rt-PA)-induced fibrinolysis in human fresh whole blood assessed as thrombus dissolution within 30 mins after reaching maximum amplitude (LY30) by thromboelastography analysis	Discovery of BT-114143, a Novel and Potent Phosphoric Acid-Containing Small-Molecule Plasminogen Activation Inhibitor for Hyperfibrinolysis. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6339	CHO 1-15 500	Transformed cell line	Female
CVCL_V634	JH-2/TPA	Cancer cell line	Male
CVCL_V643	CHL-2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00187408	PHASE4	COMPLETED	The D-KAF (Dalteparin in Knee-to-Ankle Fracture) Trial
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00214929	PHASE4	UNKNOWN	Home Treatment of Pulmonary Embolism
NCT00233740	PHASE4	COMPLETED	Protection From Pulmonary Embolism With the Permanent OptEase™ Filter (PROOF)
NCT00264277	PHASE4	COMPLETED	D-dimer to Establish Duration of Anticoagulation After Venous Thromboembolism
NCT00351754	PHASE4	COMPLETED	Detection of Pulmonary Embolism With CECT
NCT00365950	PHASE4	COMPLETED	3 Months’ Versus 6 Months’ Anticoagulation in Patients With DVT and/or PE
NCT00377091	PHASE4	WITHDRAWN	Is Using Fondaparinux (Blood Thinner) to Treat Lung Clot Cheaper Than Traditional Therapy
NCT00381511	PHASE4	COMPLETED	Deferment of Imaging for Pulmonary Embolism
NCT00442234	PHASE4	COMPLETED	Post-marketing Study of Monteplase (Cleactor) in Patients With Acute Pulmonary Embolism
NCT00457158	PHASE4	COMPLETED	PREPIC 2 : Prevention of Recurrent Pulmonary Embolism by Vena Cava Interruption
NCT00511173	PHASE4	COMPLETED	Comparison of Warfarin Dosing Using Decision Model Versus Pharmacogenetic Algorithm
NCT00586287	PHASE4	COMPLETED	Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon
NCT00603317	PHASE4	COMPLETED	Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
NCT00711308	PHASE4	COMPLETED	Tinzaparin in the Treatment of the Acute Pulmonary Embolism
NCT00781378	PHASE4	COMPLETED	Low Dosage of rt-PA in the Treatment of Pulmonary Thromboembolism in China
NCT00796692	PHASE4	COMPLETED	Nadroparin for the Initial Treatment of Pulmonary Thromboembolism
NCT00799968	PHASE4	COMPLETED	12-h and 2-h Urokinase Regimes of Pulmonary Thromboembolism in China
NCT00968929	PHASE4	COMPLETED	Recombinant Streptokinase Versus Urokinase in Pulmonary Embolism in China (RESUPEC)
NCT01014156	PHASE4	COMPLETED	Epoprostenol in Pulmonary Embolism
NCT01104337	PHASE4	COMPLETED	Drug Interaction Between Paracetamol and Warfarin
NCT01134068	PHASE4	COMPLETED	Age-adjusted D-dimer Cut-off Levels to Rule Out Pulmonary Embolism
NCT01252420	PHASE4	UNKNOWN	Two Weeks of Low Molecular Weight Heparin for Distal Vein Thrombosis
NCT01531829	PHASE4	UNKNOWN	Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD
NCT01610141	PHASE4	UNKNOWN	Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients
NCT01638468	PHASE4	TERMINATED	Multicenter, Nonrandomized, Prospective Study of Pulmonary Embolism Removal With the AngioJet 6F Ultra System
NCT01729559	PHASE4	COMPLETED	Venous Thromboembolic Prophylaxis After Trauma: Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin
NCT01828697	PHASE4	COMPLETED	Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy
NCT02029456	PHASE4	UNKNOWN	Low Dose Prolonged Infusion of Tissue Type Plasminogen Activator Therapy in Massive Pulmonary Embolism
NCT02132689	PHASE4	COMPLETED	Comparison of Thrombgolytic and Anticoagulation Therapy in Submassive Pulmonary Embolism
NCT02161965	PHASE4	COMPLETED	Vascular CalcIfiCation and sTiffness Induced by ORal antIcoAgulation
NCT02234375	PHASE4	WITHDRAWN	Use of Gadolinium in CT Pulmonary Angiography
NCT02474212	PHASE4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02476526	PHASE4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02483143	PHASE4	COMPLETED	NAC, NaHCO3 and NS Prophylaxis for CTPA in the ED on Suspicion of PE: A Randomized Controlled Trial
NCT02506985	PHASE4	TERMINATED	XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis
NCT02531581	PHASE4	COMPLETED	Diuretic Vascular Filling in the Initial Management of Acute PE With Right Ventricular Dysfunction Normotensive
NCT02584660	PHASE4	COMPLETED	A Study of Rivaroxaban for Early Discharge of Low Risk Pulmonary Embolism From the Emergency Department
NCT02596555	PHASE4	TERMINATED	Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism.
NCT02644473	PHASE4	WITHDRAWN	Safety of Topical Tranexamic Acid in Total Joint Arthroplasty in High Risk Patients