PLG

Summary

PLG (plasminogen, HGNC:9071) is a protein-coding gene on chromosome 6q26, encoding Plasminogen (P00747). Protease which primary function is to degrade fibrin, the main component of blood clots.

The plasminogen protein encoded by this gene is a serine protease that circulates in blood plasma as an inactive zymogen and is converted to the active protease, plasmin, by several plasminogen activators such as tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562. Plasmin cleavage also releases the angiostatin protein which inhibits angiogenesis. Plasmin degrades many blood plasma proteins, including fibrin-containing blood clots. As a serine protease, plasmin cleaves many products in addition to fibrin such as fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin is inactivated by proteins such as alpha-2-macroglobulin and alpha-2-antiplasmin in addition to inhibitors of the various plasminogen activators. Plasminogen also interacts with plasminogen receptors which results in the retention of plasmin on cell surfaces and in plasmin-induced cell signaling. The localization of plasminogen on cell surfaces plays a role in the degradation of extracellular matrices, cell migration, inflamation, wound healing, oncogenesis, metastasis, myogenesis, muscle regeneration, neurite outgrowth, and fibrinolysis. This protein may also play a role in acute respiratory distress syndrome (ARDS) which, in part, is caused by enhanced clot formation and the suppression of fibrinolysis. Compared to other mammals, the cluster of plasminogen-like genes to which this gene belongs has been rearranged in catarrhine primates.

Source: NCBI Gene 5340 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypoplasminogenemia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 34 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 629 total — 15 pathogenic, 14 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 16 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 34
• Drug target: yes — 8 curated mechanism-of-action drugs; 11 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 6 — Aminocaproic Acid, Anistreplase, Aprotinin, +3 more
• Constraint (gnomAD): pLI 0.17 (intermediate), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_000301
• Interaction hub: 2,588 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9071
Approved symbol	PLG
Name	plasminogen
Location	6q26
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000122194
Ensembl biotype	protein_coding
OMIM	173350
Entrez	5340

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 32 protein_coding, 16 nonsense_mediated_decay, 5 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000308192

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 4: 1, TSL 5: 4

ENST00000308192, ENST00000297289, ENST00000366924, ENST00000418964, ENST00000461414, ENST00000462918, ENST00000467466, ENST00000471691, ENST00000483038, ENST00000484367, ENST00000493435, ENST00000494325, ENST00000706906, ENST00000706907, ENST00000872428, ENST00000872429, ENST00000872430, ENST00000872431, ENST00000872432, ENST00000872433, ENST00000872434, ENST00000872435, ENST00000872436, ENST00000872437, ENST00000872438, ENST00000872439, ENST00000872440, ENST00000957675, ENST00000993682, ENST00000993684, ENST00000993686, ENST00000993687, ENST00000993688, ENST00000993690, ENST00000993691, ENST00000993697, ENST00000993700, ENST00000993702, ENST00000993703, ENST00000993711, ENST00000993712, ENST00001101967, ENST00001106666, ENST00001106667, ENST00001112337, ENST00001112338, ENST00001120096, ENST00001120097, ENST00001120098, ENST00001120099, ENST00001120100, ENST00001120101, ENST00001120102, ENST00001129851, ENST00001129852, ENST00001133725

RefSeq mRNA: 2 — MANE Select: NM_000301 NM_000301, NM_001168338

CCDS: CCDS5279, CCDS55074

Canonical transcript exons

ENST00000308192 — 19 exons

Exon	Start	End
ENSE00001666516	160712986	160713125
ENSE00001864790	160752900	160754097
ENSE00001900502	160702244	160702353
ENSE00003461840	160711077	160711191
ENSE00003567290	160707700	160707806
ENSE00003636923	160706407	160706542
ENSE00003997380	160731051	160731232
ENSE00003997383	160716645	160716763
ENSE00003997384	160752115	160752260
ENSE00003997385	160718693	160718838
ENSE00003997388	160741311	160741417
ENSE00003997390	160731745	160731893
ENSE00003997391	160733995	160734088
ENSE00003997392	160714794	160714914
ENSE00003997393	160718294	160718456
ENSE00003997394	160738538	160738612
ENSE00003997397	160739068	160739208
ENSE00003997400	160736887	160737007
ENSE00003997402	160722408	160722567

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0792 / max 43.1083, expressed in 7 samples.

Highest expression (Bgee): lobe of liver, liver, adult organism, adult mammalian kidney, nephron tubule.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLG is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Frontal Cortex BA9	eqtl	1.9e-16	+0.56	6:160748707:C:T
Testis	eqtl	2.3e-12	+0.58	6:160713773:T:C
Brain Cortex	eqtl	1.6e-11	+0.53	6:160760891:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.4e-09	+0.36	6:160767986:A:C
Brain Hypothalamus	eqtl	7.2e-09	+0.51	6:160767100:A:AG
Brain Caudate basal ganglia	eqtl	3.1e-08	+0.35	6:160731417:G:A
Prostate	eqtl	6.1e-07	+0.47	6:160766817:T:TAGA
Ovary	eqtl	3.0e-06	+0.55	6:160767986:A:C
Liver	eqtl	1.7e-05	-0.14	6:160745470:C:T
Lung	eqtl	4.3e-05	+0.63	6:160714281:G:A
Brain Amygdala	eqtl	1.0e-04	+0.51	6:160731417:G:A
Pituitary	eqtl	1.2e-04	+0.45	6:160731417:G:A
Brain Anterior cingulate cortex BA24	eqtl	2.9e-04	+0.40	6:160751910:C:G
Brain Putamen basal ganglia	eqtl	1.7e-03	+0.33	6:160751910:C:G
Whole Blood	eqtl	3.5e-02	-0.43	6:160590105:C:T
Brain Hippocampus	eqtl	4.2e-02	+0.36	6:160765609:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
71031	0.0515	6
71030	0.0277	7

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.82	gold quality
liver	UBERON:0002107	99.66	gold quality
adult organism	UBERON:0007023	95.05	gold quality
adult mammalian kidney	UBERON:0000082	94.93	gold quality
nephron tubule	UBERON:0001231	91.29	gold quality
kidney epithelium	UBERON:0004819	90.41	gold quality
kidney	UBERON:0002113	88.95	gold quality
metanephric glomerulus	UBERON:0004736	87.20	gold quality
renal glomerulus	UBERON:0000074	87.17	gold quality
descending thoracic aorta	UBERON:0002345	83.63	gold quality
thoracic aorta	UBERON:0001515	83.30	gold quality
cortex of kidney	UBERON:0001225	83.28	gold quality
ascending aorta	UBERON:0001496	83.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.19	gold quality
tibial nerve	UBERON:0001323	80.08	gold quality
aorta	UBERON:0000947	79.48	gold quality
right coronary artery	UBERON:0001625	78.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.59	gold quality
adrenal tissue	UBERON:0018303	78.39	gold quality
left coronary artery	UBERON:0001626	77.85	gold quality
popliteal artery	UBERON:0002250	76.96	gold quality
tibial artery	UBERON:0007610	76.94	gold quality
coronary artery	UBERON:0001621	76.18	gold quality
colonic epithelium	UBERON:0000397	75.14	gold quality
metanephros	UBERON:0000081	75.06	gold quality
right uterine tube	UBERON:0001302	74.86	gold quality
left uterine tube	UBERON:0001303	73.93	gold quality
metanephros cortex	UBERON:0010533	73.59	gold quality
gastrocnemius	UBERON:0001388	73.49	gold quality
left ovary	UBERON:0002119	72.85	gold quality
right ovary	UBERON:0002118	72.57	gold quality
ectocervix	UBERON:0012249	71.75	gold quality
muscle of leg	UBERON:0001383	70.89	gold quality
body of uterus	UBERON:0009853	70.45	gold quality
endocervix	UBERON:0000458	70.43	gold quality
right adrenal gland cortex	UBERON:0035827	70.19	gold quality
left adrenal gland	UBERON:0001234	69.38	gold quality
left adrenal gland cortex	UBERON:0035825	69.32	gold quality
right adrenal gland	UBERON:0001233	69.27	gold quality
right lung	UBERON:0002167	69.21	gold quality
renal medulla	UBERON:0000362	69.11	gold quality
smooth muscle tissue	UBERON:0001135	68.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.57	gold quality
gall bladder	UBERON:0002110	68.37	gold quality
lymph node	UBERON:0000029	67.95	gold quality
adrenal cortex	UBERON:0001235	67.46	gold quality
adrenal gland	UBERON:0002369	67.41	gold quality
ovary	UBERON:0000992	67.11	gold quality
vagina	UBERON:0000996	66.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.89	gold quality
lower esophagus	UBERON:0013473	66.88	gold quality
prostate gland	UBERON:0002367	66.15	gold quality
granulocyte	CL:0000094	65.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	65.69	gold quality
skeletal muscle organ	UBERON:0014892	65.52	gold quality
muscle organ	UBERON:0001630	65.51	gold quality
upper lobe of left lung	UBERON:0008952	65.39	gold quality
esophagus	UBERON:0001043	65.19	gold quality
nucleus accumbens	UBERON:0001882	65.05	gold quality
skin of abdomen	UBERON:0001416	64.92	gold quality
minor salivary gland	UBERON:0001830	64.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	64.75	gold quality
esophagus mucosa	UBERON:0002469	64.17	gold quality
right frontal lobe	UBERON:0002810	63.92	gold quality
fundus of stomach	UBERON:0001160	63.89	gold quality
upper lobe of lung	UBERON:0008948	63.85	gold quality
omental fat pad	UBERON:0010414	63.85	gold quality
peritoneum	UBERON:0002358	63.82	gold quality
skin of leg	UBERON:0001511	63.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.40	gold quality
sural nerve	UBERON:0015488	63.38	gold quality
body of stomach	UBERON:0001161	63.24	gold quality
anterior cingulate cortex	UBERON:0009835	62.81	gold quality
cingulate cortex	UBERON:0003027	62.75	gold quality
body of pancreas	UBERON:0001150	62.69	gold quality
mouth mucosa	UBERON:0003729	62.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.62	gold quality
adipose tissue of abdominal region	UBERON:0007808	62.58	gold quality
cortical plate	UBERON:0005343	62.31	gold quality
stomach	UBERON:0000945	62.25	gold quality
saliva-secreting gland	UBERON:0001044	62.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.06	gold quality
putamen	UBERON:0001874	61.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.90	gold quality
female reproductive system	UBERON:0000474	61.80	gold quality
transverse colon	UBERON:0001157	61.64	gold quality
anatomical system	UBERON:0000467	61.50	gold quality
lower esophagus mucosa	UBERON:0035834	61.40	gold quality
cerebellar cortex	UBERON:0002129	61.37	gold quality
cerebellar hemisphere	UBERON:0002245	61.33	gold quality
spinal cord	UBERON:0002240	61.26	gold quality
multicellular organism	UBERON:0000468	61.25	gold quality
material anatomical entity	UBERON:0000465	61.23	gold quality
ventricular zone	UBERON:0003053	61.11	gold quality
caudate nucleus	UBERON:0001873	61.08	gold quality
zone of skin	UBERON:0000014	61.01	gold quality
uterine cervix	UBERON:0000002	60.99	gold quality
amygdala	UBERON:0001876	60.72	gold quality
hypothalamus	UBERON:0001898	60.37	gold quality
apex of heart	UBERON:0002098	60.27	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	64.02
E-CURD-119	yes	55.22
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 61 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	2479.5	not detected
Kidney	tissue	222.5	medium
Olfactory bulb	tissue	7.0
Cerebellum	tissue	6.5	not detected
Corpus callosum	tissue	6.0
Cerebral cortex	tissue	5.7	not detected
Insular cortex	tissue	5.7
Amygdala	tissue	5.1
Retrosplenial and cingulate cortex	tissue	5.1
Retrosplenial cortex	tissue	5.1
Basal ganglia	tissue	4.8	not detected
Occipital cortex	tissue	4.7
Temporal cortex	tissue	4.6
Prefrontal cortex	tissue	4.5
Hippocampal formation	tissue	4.5
Entorhinal cortex	tissue	4.4
Ventral forebrain	tissue	4.4
Motor cortex	tissue	4.3
Putamen	tissue	4.2
Periaqueductal gray	tissue	3.9
Septum	tissue	3.9
Somatosensory cortex	tissue	3.7
Substantia nigra	tissue	3.6
Spinal cord	tissue	3.6
Hypothalamus	tissue	3.5
Midbrain	tissue	3.3
Medulla oblongata	tissue	3.2
Superior colliculi	tissue	2.8
Pons	tissue	2.6
Thalamus	tissue	2.6
Fallopian tube	tissue	2.2	not detected
Nucleus accumbens	tissue	1.8
Locus coeruleus	tissue	1.8
Salivary gland	tissue	1.3	not detected
Hippocampus	tissue	1.3	not detected
Lymph node	tissue	1.2	not detected
Postcentral gyrus	tissue	1.0
Prostate	tissue	0.9	not detected
Placenta	tissue	0.7	medium
Adrenal gland	tissue	0.7	not detected
Adipose tissue	tissue	0.6	not detected
Lung	tissue	0.6	not detected
Gallbladder	tissue	0.6	not detected
Skin 1	tissue	0.5	not detected
Choroid plexus	tissue	0.5
Testis	tissue	0.4	not detected
Endometrium 1	tissue	0.4	not detected
Stomach 1	tissue	0.3	not detected
Skeletal muscle	tissue	0.3	not detected
Epididymis	tissue	0.3	not detected
Duodenum	tissue	0.3	not detected
Appendix	tissue	0.3	not detected
Retina	tissue	0.2
Ovary	tissue	0.2	not detected
Esophagus	tissue	0.2	not detected
Small intestine	tissue	0.2	not detected
Cervix	tissue	0.1	not detected
Vagina	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (6.0), Dorsal hippocampus (4.5), Subiculum (4.3), Ventral hippocampus (4.3), Dorsal spinal cord (3.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, HIF1A, HMGA2, HOXB2, KLF5, KLF6, NFKBIB, NR0B1, RORA, SP1, SPDEF, SRF

miRNA regulators (miRDB)

Targeting PLG by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 42 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
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-1236-3P	99.94	68.04	1695
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-1301-3P	98.64	68.27	1071

Functional genomics

gnomAD constraint: pLI 0.167, LOEUF 0.559, missense Z 1.51 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000308192 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:160,702,305–160,752,247	854 / 932.1	0.92	no
6:160,752,248–160,753,058	37 / 71.5	0.52	no

Literature-anchored findings (GeneRIF, showing 40)

• Angiostatin, an angiogenesis inhibitor, lowers intracellular pH in cultured endothelial cells under conditions of low extracellular pH, resulting in a decrease in cell migration and an increase in cell death. (PMID:11888684)
• Streptokinase (SK) and staphylokinase activate human plasminogen (PMID:12016220)
• Tissue factor is the receptor for plasminogen type 1, containing both N-linked and O-linked oligosaccharide chains, on 1-LN human prostate cancer cells. (PMID:12036889)
• substrate specificity of micro-plasminogen (PMID:12080056)
• plasmin induction of MCP-1 and CD40 in human monocytes via p38 MAPK and janus kinase/STAT signaling pathways (PMID:12093796)
• Data show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. (PMID:12192005)
• Angiostatin inhibited HGF-induced phosphorylation of c-met, Akt, and ERK1/2. Angiostatin also significantly inhibited proliferation of human umbilical vein endothelial cells (HUVECs) induced by HGF. (PMID:12406896)
• investigation of clotting role of Kringle-1 domain from human plasminogen (PMID:12646571)
• Data suggest that dysplasminogenemia (congenital deficiency of plasminogen and molecular abnormality of plasminogen) may be a risk factor for deep vein thrombosis in the Korean population. (PMID:12692411)
• investigation of the mechanism of inhibition of plasminogen activation by lipoprotein(a) (PMID:12697748)
• Evidence is reviewed for plasminogen binding in the tumor environment; the known intrinsic functional relationship between plasminogen conformation and activation is essentially connected to cellular binding. (PMID:12700073)
• The voltage-dependent anion channel is a receptor for plasminogen kringle 5 on endothelial cells. (PMID:12736244)
• plasmin converts cell-bound Glu-plasminogen to Lys-plasminogen and this enzyme is produced by activation of monocytoid plasminogen by endogenous monocytoid plasminogen activators to enhance plasminogen activation on the monocytoid cell surface (PMID:12871329)
• A new plasminogen intron F-14T>G mutation, which was found to reduce the acceptor splicing site prediction score, suggesting a role in reducing the amount of correct plasminogen mRNA. (PMID:12876630)
• Computer model of the interaction of human TFPI-2 Kunitz-type serine protease inhibitor with human plasmin [letter] (PMID:14678821)
• presence of angiostatin in ascitic and pleural effusions from cancer patients (PMID:14719094)
• Early plasmin generation does not seem to play a role in the subsequent activation of other inflammatory pathways during human endotoxemia. (PMID:14739127)
• assembly of Plg and uPA on integrin alpha(M)beta(2) regulates Plm activity and, thereby, plays a crucial role in neutrophil-mediated thrombolysis (PMID:14769799)
• Plasminogen is an adhesive ligand for integrins alphaMbeta2 and alpha5beta1. (PMID:15090462)
• A deficiency of plasminogen reduces processing of beta-endorphin and alpha-melanocyte stimulating hormone, and interferes with normal brain function. (PMID:15099286)
• Lys-698 of human Pg plays a functional role in the so-called N-terminal insertion activation mechanism by streptokinase. (PMID:15211511)
• analysis of the kinetic mechanism in which SK binding and reversible conformational activation of plasminogen occur in a rapid equilibrium, multistep process (PMID:15215240)
• Plasminogen is bound to the cell surface by histidine-rich glycoprotein (PMID:15220341)
• Plasminogen binding in the presence of the urokinase-type plasminogen activator (uPA) promoted the invasion of HeLa cells by Mycoplasma fermentans (PMID:15321992)
• a transgene expressing human plasminogen markedly increased mortality in mice infected with group A streptococci, and this susceptibility was dependent on bacterial streptokinase expression (PMID:15333838)
• binds to Streptococcus mutans alpha-enolase (PMID:15501816)
• studies of a 1:1 complex formed by the cellular conformation of the sheep prion protein with human plasminogen; effects of pressure, temperature and presence/absence of proteolytic inhibitors (PMID:15529749)
• recombinant PrPc binds to human plasminogen (PMID:15609351)
• histidine-proline-rich glycoprotein can act as either a positive or negative effector of Plg activation in vitro (PMID:15613921)
• plasminogen binds with high affinity to IGF-II and IGF-binding protein-3 (PMID:15642732)
• Data show that bacillolysin MA (BL-MA)affects blood coagulation and fibrinolysis systems and can be used to produce angiostatin-like plasminogen fragments and active serine proteases of human plasma [BL-MA]. (PMID:15677446)
• angiostatin and plasminogen share binding to endothelial cell surface actin and, therefore, that angiostatin has the potential to inhibit plasmin-dependent processes such as cell migration-movement (PMID:15746964)
• associations suggest that PLG has the potential to simultaneously regulate calcium signaling pathways and Na+/H+ exchanges necessary for tumor cell proliferation and invasiveness (PMID:15911629)
• Plasmin and thrombin accelerate shedding of syndecan-4 ectodomain, which generates cleavage sites at Lys(114)-Arg(115) and Lys(129)-Val(130) bonds (PMID:16087677)
• The effect of conformation on the initial and secondary cleavages of plasminogen to generate active angiostatins is reported. (PMID:16097950)
• Protein S plays a role in cell-associated plasminogen activation and invasive potential of inflammatory cells. (PMID:16229836)
• The cytoprotective effect of plasminogen requires plasmin proteolytic activity and requires PAR1 (PMID:16478887)
• angiostatins K1-3, K1-4 and K1-4.5 mediate anti-angiogenesis in a process involvingp53, FasL, AKT and mRNA deregulation (PMID:16601838)
• propose that the human plasminogen system plays a critical role in group A streptococcal M1T1 systemic disease initiation. (PMID:16790522)
• Ca (2+) -dependent and -independent binding of Lys-Pg to FXa33/13 are C-terminal lysine-dependent. The N-terminal 1 - 77 amino acids of Glu-Pg confer significant C-terminal lysine-independent binding, which may play a role in PLG activation (PMID:17200769)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plg	ENSDARG00000023111
mus_musculus	Plg	ENSMUSG00000059481
rattus_norvegicus	Plg	ENSRNOG00000017223

Paralogs (14): PRSS33 (ENSG00000103355), PLAT (ENSG00000104368), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022), PRSS50 (ENSG00000283706)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97620) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 64 distinct phenotype terms.

Mouse phenotype (MP)	Records
rectal prolapse	5
premature death	4
abnormal rectum morphology	3
decreased body weight	3
gastric ulcer	3
liver fibrosis	3
abnormal liver morphology	2
abnormal lung morphology	2
impaired wound healing	2
reduced female fertility	2
abnormal blood coagulation	2
perianal ulcer	2
abnormal thrombosis	2
abnormal stomach morphology	1
abnormal colon morphology	1
intestinal ulcer	1
abnormal mammary gland development	1
enlarged lymph nodes	1
abnormal vagina morphology	1
abnormal body weight	1
weight loss	1
abnormal conjunctiva morphology	1
abnormal cornea morphology	1
hepatic necrosis	1
postnatal growth retardation	1

+39 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Tropidechis carinatus	P81428	99.3%	Diamond
Notechis scutatus scutatus	P82807	99.3%	Diamond
Pongo abelii	Q5R5E8	99.3%	Diamond
Canis lupus familiaris	Q867B7	97.7%	Diamond
Hoplocephalus stephensii	P83370	97.6%	Diamond
Bos taurus	Q76BS1	97.4%	Diamond
Oxyuranus microlepidotus	Q58L95	95.1%	Diamond
Oxyuranus scutellatus	Q58L96	95.1%	Diamond
Macaca mulatta	O19023	94.2%	Diamond
Macaca fascicularis	O46644	94.2%	Diamond
Capra ibex	B6E141	93.8%	Diamond
Pseudonaja textilis	Q1L659	93.6%	Diamond
Capra hircus	Q7M323	92.9%	Diamond
Papio cynocephalus	P16227	92.6%	Diamond
Rhinella arenarum	Q66TN7	90.6%	Diamond
Desmodus rotundus	P15638	89.9%	Diamond
Felis catus	Q5R1M5	89.9%	Diamond
Sus scrofa	P00772	89.5%	Diamond
Acropora millepora	B8V7S0	87.4%	Diamond
Ovis aries	P81286	86.3%	Diamond
Pseudechis porphyriacus	Q58L93	86.1%	Diamond
Demansia vestigiata	A6MFK7	85.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MAP3K4-AS1	ncRNA	117981787
MAP3K4	protein-coding	4216
AGPAT4	protein-coding	56895
LPA	protein-coding	4018
SLC22A3	protein-coding	6581

Protein

Protein identifiers

Plasminogen — P00747 (reviewed: P00747)

All UniProt accessions (6): A0A9L9PXP2, A0A9L9PY04, A0A9L9PYG2, A6PVI2, P00747, Q5TEH5

UniProt curated annotations — full annotation on UniProt →

Function. Protease which primary function is to degrade fibrin, the main component of blood clots. Also cleaves other components of blood clots like thrombospondin-1/THBS1 and von Willebrand factor/VWF. Can also directly and/or through the activation of other proteases degrade the various components of the extracellular matrix including collagen, fibronectin and laminin. Thereby, regulates a variety of biological processes including embryonic development, tissue remodeling, and inflammation. In ovulation, weakens the walls of the Graafian follicle. In vitro, it is also able to cleave several complement zymogens, such as C1, C4 and C5. Has an antiangiogenic activity and inhibits neovascularization. Could act through the inhibition of the ATP synthase subunit ATP5F1A. (Microbial infection) Binds to OspC on the surface of B.burgdorferi cells, possibly conferring an extracellular protease activity on the bacteria that allows it to traverse host tissue. (Microbial infection) Interacts with dengue virus type 2 particles. Enhances dengue virus type 2 infection in Aedes aegypti mosquito midgut by increasing midgut internalization, resulting in higher infection rates and viral dissemination in mosquitoes.

Subunit / interactions. The active form of plasmin is a two-chain monomeric protein, not oligomerized, consisting of a heavy chain (A) and a light chain (B) that are covalently linked by disulfide bonds. Interacts with CSPG4; enhances the activation of plasminogen by urokinase-type (PLAU) plasminogen activator. Interacts with AMOT. Interacts (via the Kringle domains) with HRG; the interaction tethers PLG to the cell surface and enhances its activation. Interacts (via Kringle 4 domain) with ADA; the interaction stimulates PLG activation when in complex with DPP4. Interacts with ATP5F1A; the interaction could inhibit ATP5F1A and explain the antiangiogenic activity of angiostatin. Interacts with CSPG4; blocks the antiangiogenic activity of angiostatin. Interacts with AMOT. (Microbial infection) Interacts (plasmin) with Kazal-type trypsin inhibitor, a serine protease inhibitor from Aedes aegypti. (Microbial infection) Interacts (plasmin) with and is inhibited by iripin-8, a serine protease inhibitor from Ixodes ricinus saliva. (Microbial infection) Interacts (plasmin) with iripin-1, a serine protease inhibitor from Ixodes ricinus saliva. (Microbial infection) Interacts with C.albicans GPD2; the interaction is direct and provides active plasmin on the surface of fungal cells. (Microbial infection) Interacts with Staphylococcus aureus protein FnbB; this interaction provides active plasmin on the surface of bacterial cells. (Microbial infection) Interacts with P.falciparum (strain NF54) enolase ENO (via DKSLVK motif); the interaction occurs at the ookinete cell surface and is required for ookinete invasion of the mosquito midgut. (Microbial infection) Interacts with B.burgdorferi OspC.

Subcellular location. Secreted Secreted.

Tissue specificity. Present in plasma and many other extracellular fluids. It is synthesized in the liver.

Post-translational modifications. N-linked glycan contains N-acetyllactosamine and sialic acid. O-linked glycans consist of Gal-GalNAc disaccharide modified with up to 2 sialic acid residues (microheterogeneity). Activation requires cleavage in two chains held together by two disulfide bonds. Removal of the activation peptide is also part of the activation mechanisms. (Microbial infection) The Y.pestis Pla protein cleaves between Arg-580 and Val-581, generating plasmin which facilitates bacterial migration and infection.

Disease relevance. Plasminogen deficiency (PLGD) [MIM:217090] A disorder characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The disease is caused by variants affecting the gene represented in this entry. Angioedema, hereditary, 4 (HAE4) [MIM:619360] A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE4 is an autosomal dominant form with incomplete penetrance, variable expressivity, and female predominance. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Converted into plasmin by tissue-type (PLAT) and urokinase-type (PLAU) plasminogen activator. The activation by PLAT is enhanced by fibrin at the surface of blood clots. The partial proteolysis of fibrin by plasmin mainly exposes C-terminal lysine residues which in turn help recruit and activate plasminogen. The activation by PLAU occurs at the surface of cells and is more specific of extracellular matrix remodeling. Activated by streptokinase. Plasmin activity is also inhibited by SERPINF2; plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot.

Domain organisation. Kringle domains mediate interaction with CSPG4.

Similarity. Belongs to the peptidase S1 family. Plasminogen subfamily.

RefSeq proteins (2): NP_000292, NP_001161810 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR003609	Pan_app	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR023317	Pept_S1A_plasmin	Family
IPR033116	TRYPSIN_SER	Active_site
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR050759	Serine_protease_kringle	Family

Pfam: PF00024, PF00051, PF00089

Enzyme classification (BRENDA)

• EC 3.4.21.7 — plasmin (BRENDA: 7 organisms, 175 substrates, 293 inhibitors, 68 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
D-NORLEUCYL-HEXAHYDROTYROSYL-LYSINE-P-NITROANILI	0.0059–0.1311	13
D-VAL-L-LEU-L-LYS-4-NITROANILIDE	0.138–0.325	4
D-VAL-LEU-LYS-P-NITROANILIDE	0.21–1.26	4
TOSYL-ARG METHYL ESTER	5.3–7	4
BENZYLOXYCARBONYL-LYS-P-NITROPHENYL ESTER	0.0135–0.083	3
4-NITROPHENYL-P’-(GUANIDINIUM)BENZOATE BROMIDE	0.0052–0.0113	2
GIYRSR	0.002–0.0058	2
P-NITROPHENYL-P’-(METHYLETHYLSULFONIUMMETHYL)BEN	0.214–0.258	2
P-NITROPHENYL-P’-(PYRIDINIUMMETHYL)-BENZOATE	0.21–0.23	2
P-NITROPHENYL-P’-(THIOURONIUMMETHYL)BENZOATE	0.027–0.043	2
AIYRSR	0.003	1
CIYRSR	0.004	1
D-ILE-PHE-LYS	0.02	1
FIBRINOGEN	0.03	1
GIVRSR	0.012	1

UniProt features (174 total): strand 59, disulfide bond 24, sequence variant 21, helix 18, turn 13, domain 7, binding site 6, chain 5, sequence conflict 5, active site 3, site 3, glycosylation site 3, region of interest 2, modified residue 2, signal peptide 1, propeptide 1, mutagenesis site 1

Structure

Experimental structures (PDB)

showing 30 of 49 structures by resolution:

PDB	Title	Method	Resolution (Å)
5UGG	Protease Inhibitor	X-RAY DIFFRACTION	1.2
6D3Y	Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 …	X-RAY DIFFRACTION	1.32
5UGD	Protease Inhibitor	X-RAY DIFFRACTION	1.38
6D40	Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 …	X-RAY DIFFRACTION	1.43
8F7U	Macrocyclic Plasmin Inhibitor	X-RAY DIFFRACTION	1.47
7UAH	Macrocyclic plasmin inhibitor	X-RAY DIFFRACTION	1.57
8F7V	Macrocyclic plasmin inhibitor	X-RAY DIFFRACTION	1.65
5HPG	STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN	X-RAY DIFFRACTION	1.66
1KRN	STRUCTURE OF KRINGLE 4 AT 4C TEMPERATURE AND 1.67 ANGSTROMS RESOLUTION	X-RAY DIFFRACTION	1.67
6OG4	plasminogen binding group A streptococcal M protein	X-RAY DIFFRACTION	1.7
1KI0	The X-ray Structure of Human Angiostatin	X-RAY DIFFRACTION	1.75
4CIK	plasminogen kringle 1 in complex with inhibitor	X-RAY DIFFRACTION	1.78
6D3X	Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 …	X-RAY DIFFRACTION	1.8
7THS	Macrocyclic plasmin inhibitor	X-RAY DIFFRACTION	1.8
1PK4	CRYSTAL AND MOLECULAR STRUCTURE OF HUMAN PLASMINOGEN KRINGLE 4 REFINED AT 1.9-ANGSTROMS …	X-RAY DIFFRACTION	1.9
7E50	Crystal structure of human microplasmin in complex with kazal-type inhibitor AaTI	X-RAY DIFFRACTION	1.95
1DDJ	CRYSTAL STRUCTURE OF HUMAN PLASMINOGEN CATALYTIC DOMAIN	X-RAY DIFFRACTION	2
1QRZ	CATALYTIC DOMAIN OF PLASMINOGEN	X-RAY DIFFRACTION	2
6D3Z	Protease SFTI complex	X-RAY DIFFRACTION	2
4DCB	Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop …	X-RAY DIFFRACTION	2.03
1CEA	THE STRUCTURE OF THE NON-COVALENT COMPLEX OF RECOMBINANT KRINGLE 1 DOMAIN OF HUMAN …	X-RAY DIFFRACTION	2.06
1CEB	THE STRUCTURE OF THE NON-COVALENT COMPLEX OF RECOMBINANT KRINGLE 1 DOMAIN OF HUMAN …	X-RAY DIFFRACTION	2.07
9AZK	Macrocyclic inhibitors targeting the prime site of the fibrinolytic serine protease …	X-RAY DIFFRACTION	2.1
1PMK	KRINGLE-KRINGLE INTERACTIONS IN MULTIMER KRINGLE STRUCTURES	X-RAY DIFFRACTION	2.25
2PK4	THE REFINED STRUCTURE OF THE EPSILON-AMINOCAPROIC ACID COMPLEX OF HUMAN PLASMINOGEN …	X-RAY DIFFRACTION	2.25
1L4D	CRYSTAL STRUCTURE OF MICROPLASMINOGEN-STREPTOKINASE ALPHA DOMAIN COMPLEX	X-RAY DIFFRACTION	2.3
1RJX	Human PLASMINOGEN CATALYTIC DOMAIN, K698M MUTANT	X-RAY DIFFRACTION	2.3
2DOH	The X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound a …	X-RAY DIFFRACTION	2.3
6Q1U	Structure of plasmin and peptide complex	X-RAY DIFFRACTION	2.35
4DUR	The X-ray Crystal Structure of Full-Length type II Human Plasminogen	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00747-F1	83.53	0.46

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Metabolic proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH supported · IF approved

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 (6)

Position	Role
622	charge relay system
665	charge relay system
760	charge relay system
78–79	cleavage; by stromelysin-1/mmp3
466–467	cleavage; by stromelysin-1/mmp3
580–581	cleavage; by plasminogen activators plau and plat

Ligand- & substrate-binding residues (6)

Position	Role
134	a protein
136	a protein
158	a protein
172	a protein
432	a protein
445	a protein

Post-translational modifications (2)

Type	Positions
Phosphoserine	597, 688

Disulfide bonds (24)

Type	Positions
Disulfide bond	49–73, 53–61, 103–181, 124–164, 152–176, 185–262, 188–316, 206–245, 234–257, 275–352, 296–335, 324–347, 377–454, 398–437, 426–449, 481–560, 502–543, 531–555, 607–623, 699–766, 729–745, 756–784
Interchain (between plasmin heavy a and plasmin light b chains)	567–685, 577–585

Glycosylation sites (3)

Type	Positions
O-linked (galnac…) serine	268
N-linked (glcnac…) asparagine	308
O-linked (galnac…) threonine	365

Mutagenesis-validated functional residues (1)

Position	Phenotype
741	loss of serine-type endopeptidase activity. proteolytically cleaved, but loss of cell detachment.

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-1592389	Activation of Matrix Metalloproteinases	curated
R-HSA-75205	Dissolution of Fibrin Clot	curated
R-HSA-114608	Platelet degranulation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-186797	Signaling by PDGF	curated
R-HSA-1474228	Degradation of the extracellular matrix	electronic
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-109582	Hemostasis	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-76005	Response to elevated platelet cytosolic Ca2+	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—

MSigDB gene sets: 370 (showing top): MODULE_172, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_CELL_CELL_ADHESION_MEDIATED_BY_CADHERIN, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GNF2_HPN, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_REGENERATION, HNF1_Q6

GO Biological Process (14): proteolysis (GO:0006508), blood coagulation (GO:0007596), negative regulation of cell-substrate adhesion (GO:0010812), extracellular matrix disassembly (GO:0022617), collagen catabolic process (GO:0030574), fibrinolysis (GO:0042730), positive regulation of blood vessel endothelial cell migration (GO:0043536), tissue remodeling (GO:0048771), biological process involved in interaction with symbiont (GO:0051702), negative regulation of fibrinolysis (GO:0051918), positive regulation of fibrinolysis (GO:0051919), trans-synaptic signaling by BDNF, modulating synaptic transmission (GO:0099183), negative regulation of cell-cell adhesion mediated by cadherin (GO:2000048), hemostasis (GO:0007599)

GO Molecular Function (14): protease binding (GO:0002020), endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), serine-type peptidase activity (GO:0008236), enzyme binding (GO:0019899), kinase binding (GO:0019900), protein domain specific binding (GO:0019904), apolipoprotein binding (GO:0034185), protein-folding chaperone binding (GO:0051087), protein antigen binding (GO:1990405), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (10): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Hemostasis	2
Response to elevated platelet cytosolic Ca2+	1
Extracellular matrix organization	1
Degradation of the extracellular matrix	1
Signaling by Receptor Tyrosine Kinases	1
Metabolism of proteins	1
Platelet activation, signaling and aggregation	1
Signal Transduction	1

GO top-level categories

52 GO namespaces:

Category	Terms
protein binding	6
cellular anatomical structure	3
negative regulation of blood coagulation	2
fibrinolysis	2
regulation of fibrinolysis	2
enzyme binding	2
peptidase activity	2
synapse	2
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
negative regulation of cell adhesion	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
cellular component disassembly	1
extracellular matrix organization	1
catabolic process	1
collagen metabolic process	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
multicellular organismal process	1
biological process involved in symbiotic interaction	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
negative regulation of biological process	1
positive regulation of biological process	1
trans-synaptic signaling by BDNF	1
trans-synaptic signaling, modulating synaptic transmission	1
negative regulation of cell-cell adhesion	1
cell-cell adhesion mediated by cadherin	1
regulation of cell-cell adhesion mediated by cadherin	1
regulation of body fluid levels	1
endopeptidase activity	1
serine-type peptidase activity	1
serine hydrolase activity	1
antigen binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
external encapsulating structure	1
platelet alpha granule	1
secretory granule lumen	1
extracellular vesicle	1
extracellular region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 39 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
biological process involved in interaction with symbiont	BP	direct assay
blood coagulation	BP	mutant phenotype
collagen catabolic process	BP	direct assay
extracellular matrix disassembly	BP	direct assay
fibrinolysis	BP	direct assay
negative regulation of cell-substrate adhesion	BP	direct assay
negative regulation of fibrinolysis	BP	direct assay
positive regulation of blood vessel endothelial cell migration	BP	genetic interaction
positive regulation of fibrinolysis	BP	direct assay
proteolysis	BP	direct assay
blood microparticle	CC	high-throughput assay
cell surface	CC	direct assay
external side of plasma membrane	CC	direct assay
extracellular exosome	CC	high-throughput assay
extracellular matrix	CC	high-throughput assay
apolipoprotein binding	MF	physical interaction
endopeptidase activity	MF	direct assay
enzyme binding	MF	physical interaction
kinase binding	MF	physical interaction
protease binding	MF	physical interaction
protein antigen binding	MF	physical interaction
protein domain specific binding	MF	physical interaction
protein-folding chaperone binding	MF	physical interaction
serine-type endopeptidase activity	MF	direct assay
signaling receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,588 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLG	SERPINE1	P05121	976
PLG	SERPINF2	P08697	946
PLG	SERPINC1	P01008	937
PLG	SERPINB2	P05120	917
PLG	F3	P13726	908
PLG	CPB2	Q96IY4	894
PLG	PLAT	P00750	890
PLG	COL18A1	P39060	872
PLG	SERPINF1	P36955	860
PLG	PLAU	P00749	858
PLG	HRG	P04196	857
PLG	THBD	P07204	822
PLG	MMP9	P14780	809
PLG	FN1	P02751	807
PLG	ENO1	P06733	792

IntAct

Human interaction partners of PLG in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
FOXD4L6	physical association	0.560	3
LOX	direct interaction	0.560	2
MARVELD2	direct interaction	0.540	2
ATP2	physical association	0.520	2
APOH	direct interaction	0.440	2
APP	direct interaction	0.440	1
PCOLCE	direct interaction	0.440	1
PLGRKT	direct interaction	0.440	1
S	protein cleavage	0.440	1
DPP6	physical association	0.400	1
CYFIP2	physical association	0.370	1
EP300	physical association	0.370	1
MAPK14	physical association	0.370	1
PRDX4	physical association	0.370	1
SMAD3	physical association	0.370	1
SMAD4	physical association	0.370	1
TXN2	physical association	0.370	1
YTHDC1	physical association	0.370	1
ARHGAP20	association	0.350	1
IGHA1	association	0.350	1
RAP2A	physical association	0.000	1
RBBP6	physical association	0.000	1

BioGRID (84 interactions; top human partners by supporting records): ACTB (Far Western; 3 records), HSPA1A (Reconstituted Complex; 2 records), HSPB1 (Reconstituted Complex; 2 records), HSPD1 (Reconstituted Complex; 2 records), IGFBP3 (Reconstituted Complex; 2 records), SERPINF2 (Reconstituted Complex; 2 records), THBS1 (Reconstituted Complex; 2 records), AGPAT1 (Affinity Capture-MS), ARHGAP20 (Affinity Capture-MS), ARHGAP21 (Affinity Capture-MS), ARHGAP26 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), C7 (Reconstituted Complex), CCR1 (Affinity Capture-MS), CDC73 (Affinity Capture-MS)

SIGNOR signaling

showing 7 of 9 signaling interactions:

A	Effect	B	Mechanism
SRF	“up-regulates quantity by expression”	PLG	“transcriptional regulation”
PLAT	“up-regulates activity”	PLG	binding
PLG	“up-regulates activity”	PLAT	cleavage
PLG	up-regulates	Fibrinolysis
PLG	“down-regulates activity”	APOH	cleavage
PLG	“up-regulates activity”	F2R	cleavage
PLG	“down-regulates activity”	F2R	cleavage

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
★ IGF2R-PLG-PLAU-PLAUR-LTGFbeta1 complex	5	IGF2R, PLAU, PLAUR, PLG, TGFB1
★ IGF2R-PLAUR-PLG complex	3	IGF2R, PLAUR, PLG
★ PLAT-PLG-THBS1 complex	3	PLAT, PLG, THBS1
★ HRG-PLAT-PLG complex	3	HRG, PLAT, PLG
★ PLG-THBS1 complex	2	PLG, THBS1
★ HRG-PLG complex	2	HRG, PLG
★ PLAT-PLG complex	2	PLAT, PLG

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ITGA2B;ITGB3	ligand

Disease & clinical

Genetic variants

Variant evidence for PLG: 629 ClinVar records (29 pathogenic / likely pathogenic); 34 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	14
Uncertain significance	314
Likely benign	178
Benign	68

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 29 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
590291	NM_000301.5(PLG):c.988A>G (p.Lys330Glu)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
282782	NM_000301.5(PLG):c.185+1G>T	Pathogenic	criteria provided, single submitter	1
2001679	NM_000301.5(PLG):c.618C>A (p.Cys206Ter)	Pathogenic	criteria provided, single submitter	1
2734965	NM_000301.5(PLG):c.1468C>T (p.Arg490Ter)	Pathogenic	criteria provided, single submitter	1
3658824	NM_000301.5(PLG):c.1755T>A (p.Cys585Ter)	Pathogenic	criteria provided, single submitter	1
3717788	NM_000301.5(PLG):c.528C>A (p.Cys176Ter)	Pathogenic	criteria provided, single submitter	1
4728204	NM_000301.5(PLG):c.732G>A (p.Trp244Ter)	Pathogenic	criteria provided, single submitter	1
4747550	NM_000301.5(PLG):c.1675C>T (p.Gln559Ter)	Pathogenic	criteria provided, single submitter	1
1179096	NM_000301.5(PLG):c.2019-1G>A	Likely pathogenic	criteria provided, single submitter	1
2635544	NM_000301.5(PLG):c.1265dup (p.Met423fs)	Likely pathogenic	criteria provided, single submitter	1
2734963	NM_000301.5(PLG):c.293-2A>G	Likely pathogenic	criteria provided, single submitter	1
2980729	NM_000301.5(PLG):c.1256+1G>A	Likely pathogenic	criteria provided, single submitter	1
3381018	NM_000301.5(PLG):c.763del (p.Glu255fs)	Likely pathogenic	criteria provided, single submitter	1
3593297	NM_000301.5(PLG):c.292+1G>C	Likely pathogenic	criteria provided, single submitter	1
3593317	NM_000301.5(PLG):c.910C>G (p.Pro304Ala)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PLG’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,481):

Position(s)	Effect	Δscore	Sites
6:160707807	donor_loss	1.0000	2
6:160712984–160712985	acceptor_loss	1.0000	5
6:160714784	acceptor_gain	1.0000
6:160716643–160716644	acceptor_loss	1.0000	4
6:160718691–160718692	acceptor_loss	1.0000	5
6:160718839–160718840	donor_loss	1.0000	4
6:160722406–160722407	acceptor_loss	1.0000	5
6:160722496	donor_gain	1.0000
6:160722564	donor_gain	1.0000
6:160739201	donor_gain	1.0000

AlphaMissense

1,663 missense substitutions predicted likely pathogenic (of 5,320 scored), across 376 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D759	8	0.991	0.997
D665	8	0.963	0.986
S760	8	0.953	0.989
H605	8	0.938	0.976
N428	8	0.933	0.988
N154	8	0.920	0.988
H622	8	0.906	0.955
S597	8	0.903	0.995
N533	8	0.895	0.990
F64	8	0.885	0.979
D535	8	0.846	0.930
D754	8	0.838	0.922
H511	8	0.779	0.953
H217	8	0.735	0.882
C426	7	0.996	0.999
C607	7	0.996	0.999
C623	7	0.996	0.998
W704	7	0.996	1.000
C502	7	0.995	0.998
C531	7	0.995	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.22e-08
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000574
Liver Hepatocellular Carcinoma (validation)	favorable	0.000762

Disease associations

OMIM: gene MIM:173350 | disease phenotypes: MIM:217090, MIM:166760, MIM:619360, MIM:106100

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypoplasminogenemia	Strong	Autosomal recessive	4
angioedema, hereditary, 4	Strong	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
hypoplasminogenemia	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Fetal anomalies	green
Hydrocephalus	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Thrombophilia with a likely monogenic cause	amber

Mondo (6): hypoplasminogenemia (MONDO:0009009), dysplasminogenemia (MONDO:0100538), otitis media, susceptibility to (MONDO:0008162), angioedema, hereditary, 4 (MONDO:0025712), hereditary angioedema (MONDO:0019623), hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (4): Hypoplasminogenemia (Orphanet:722), Hereditary angioedema (Orphanet:91378), Hereditary angioedema with normal C1Inh (Orphanet:528647), Ligneous conjunctivitis (Orphanet:97231)

HPO phenotypes

34 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000123	Nephritis
HP:0000137	Abnormality of the ovary
HP:0000212	Gingival overgrowth
HP:0000230	Gingivitis
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000282	Facial edema
HP:0000370	Abnormality of the middle ear
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000509	Conjunctivitis
HP:0000618	Blindness
HP:0000704	Periodontitis
HP:0000787	Kidney stone
HP:0000951	Abnormality of the skin
HP:0001290	Generalized hypotonia
HP:0001305	Dandy-Walker malformation
HP:0001321	Cerebellar hypoplasia
HP:0001977	Abnormal thrombosis
HP:0002086	Abnormality of the respiratory system
HP:0002119	Ventriculomegaly
HP:0002588	Duodenal ulcer
HP:0002788	Recurrent upper respiratory tract infections
HP:0003593	Infantile onset
HP:0011027	Abnormal fallopian tube morphology
HP:0011462	Young adult onset
HP:0012027	Laryngeal edema
HP:0030160	Cervicitis
HP:0031244	Swollen lip
HP:0034197	Third trimester onset
HP:0040228	Decreased circulating plasminogen concentration
HP:0100665	Angioedema

GWAS associations

showing 30 of 34 associations:

Study	Trait	p-value
GCST008079_69	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-178
GCST008079_7	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3e-175
GCST010866_90	Coronary artery disease	3e-103
GCST004787_15	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2e-49
GCST010244_56	Triglyceride levels	5e-36
GCST003116_15	Coronary artery disease	2e-32
GCST003127_15	Lipoprotein (a) levels	5e-30
GCST009881_1	Lipoprotein (a) levels in response to niacin in statin-treated individuals	7e-28
GCST002601_1	Plasma plasminogen levels	2e-26
GCST003117_17	Myocardial infarction	2e-24
GCST001218_3	Lp (a) levels	3e-17
GCST008078_95	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-11
GCST90002402_780	Platelet count	6e-11
GCST003928_3	Giant cell arteritis	1e-10
GCST008084_189	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1e-9
GCST008084_71	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1e-9
GCST010244_291	Triglyceride levels	3e-9
GCST005952_6	Body mass index (age>50)	2e-8
GCST008075_192	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3e-8
GCST003991_14	Childhood ear infection	4e-8
GCST005013_92	Childhood ear infection	4e-8
GCST008075_32	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-8
GCST008078_19	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-8
GCST008083_82	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-8
GCST008086_108	LDL cholesterol levels in current drinkers	6e-8
GCST006813_2	End stage renal disease x APOL1 genotype interaction	8e-8
GCST005950_13	Body mass index x sex x age interaction (4df test)	3e-7
GCST008074_54	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5e-7
GCST003075_9	Cognitive decline rate in late mild cognitive impairment	7e-7
GCST003075_128	Cognitive decline rate in late mild cognitive impairment	2e-6

EFO canonical traits (from GWAS)

14 canonical traits:

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0022597	aging
EFO:0006309	plasma plasminogen measurement
EFO:0007710	cognitive decline measurement
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009324	APOL1 risk genotype carrier status
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004309	platelet count

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D054179	Angioedemas, Hereditary	C14.907.079.500; C16.320.798.500.500; C17.800.862.945.066.500; C20.543.480.904.066.500; C20.673.795.500.500
C580017	Congenital Plasminogen Deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1801 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PLG protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

8 curated-mechanism drugs:

Drug	Modality	Max phase
AMINOCAPROIC ACID	Small molecule	4
ANISTREPLASE	Enzyme	4
APROTININ	Unknown	4
DEFIBROTIDE SODIUM	Oligonucleotide	4
STREPTOKINASE	Enzyme	4
TRANEXAMIC ACID	Small molecule	4
DESMOTEPLASE	Enzyme	3
AMEDIPLASE	Enzyme	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 184,296 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1046	AMINOCAPROIC ACID	4	96,126
CHEMBL877	TRANEXAMIC ACID	4	28,038
CHEMBL5189739	BEROTRALSTAT	4	7
CHEMBL266349	MELAGATRAN	4	5,456
CHEMBL55	PENTAMIDINE	4	27,197
CHEMBL231813	TELAPREVIR	4	3,453
CHEMBL48361	DABIGATRAN	3	13,643
CHEMBL87563	GABEXATE	3	2,044
CHEMBL4112929	MILVEXIAN	3	142
CHEMBL273264	NAFAMOSTAT	3	7,150
CHEMBL273196	EFEGATRAN	2	1,040

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs783145		Metabolism/PK	Allele G is associated with increased transcription of PLG in human liver samples as compared to allele A.	PMID:22006096
rs783145		Metabolism/PK	Allele G is associated with decreased transcription of PRSS55 in human liver samples as compared to allele A.	PMID:22006096

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

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

Ligand	Action	Affinity	Parameter
bis-triazole derivative 10	Inhibition	9.1	pKi
aprotinin	Binding	6.8	pIC50
WX-UK1	Inhibition	5.84	pKi
6-aminocaproic acid	Binding	4.4	pIC50
tranexamic acid	Binding	3.6	pIC50

Binding affinities (BindingDB)

1196 measured of 1549 human assays (1736 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(4-chloro-2-(5-chloropyridin-2-ylcarbamoyl)phenyl)-4-(N,N-dimethylcarbamimidoyl)-2-fluorobenzamide	KI	0.06 nM
2-(3’-Amino-5-chloro-2-hydroxy-biphenyl-3-yl)-1H-benzoimidazole-5-carboxamidine	KI	0.078 nM
CHEMBL4524734	KI	0.1 nM
1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2-(methylsulfonyl)-[1,1-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide	KI	0.15 nM
Peptide boronate	KI	0.174 nM
Peptide boronate	KI	0.187 nM
5-chloro-N-(5-chloropyridin-2-yl)-2-(4-((2-iminooxazolidin-3-yl)methyl)benzamido)benzamide	IC50	0.2 nM
CHEMBL4454304	KI	0.21 nM
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-(4-{[methyl-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-amino]-methyl}-benzoylamino)-benzamide	IC50	0.3 nM
CHEMBL4449958	IC50	0.34 nM
(2R)-N-[(3-aminobenzene)sulfonyl]-2-[(4-carbamimidoyl-3-hydroxyphenyl)amino]-2-(3,5-diethoxy-2-fluorophenyl)acetamide	KI	0.35 nM
1,3-Dibenzyl-[1,3]diazetidine-2,4-dione	IC50	0.39 nM
5-chloro-N-[(2S)-2-[[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]thiophene-2-carboxamide	IC50	0.43 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
CHEMBL4579797	KI	0.45 nM
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonyl}-S-alaninate	IC50	0.45 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
3-(1-Methyl-1H-imidazol-2-yl)propyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-[2-ethyl-3-(2-oxopyrrolidin-1-yl)benzene-1-sulfonyl]-S-alaninate hydrochloride	IC50	0.48 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
CHEMBL6192325	IC50	0.49 nM
Methyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]-sulfonyl}-S-alaninate	IC50	0.49 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.49 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
(2R,3R)-2-(3-Carbamimidoyl-benzyl)-3-[(3’-carbamoyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester	KI	0.5 nM
3-[3-(3-Benzyl-5-carbamimidoyl-1H-indol-2-yl)-5-bromo-4-hydroxy-phenyl]-propionic acid	KI	0.5 nM
Phosphoric acid mono-{2-[3-(3-benzyl-5-carbamimidoyl-1H-indol-2-yl)-5-bromo-4-hydroxy-phenyl]-ethyl} ester	KI	0.5 nM
(R)-5-Guanidino-2-phenylmethanesulfonylamino-pentanoic acid {[(R)-4-guanidino-1-(thiazole-2-carbonyl)-butylcarbamoyl]-methyl}-amide	IC50	0.5 nM
5-chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N,N-dimethyl-carbamimidoyl)-benzoylamino]-benzamide	IC50	0.5 nM
2-[4-(5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-yl]-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide	IC50	0.51 nM
Methyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-[2-ethyl-3-(2-oxopyrrolidin-1-yl)benzene-1-sulfonyl]-S-alaninate	IC50	0.54 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
CHEMBL4462811	KI	0.6 nM
CHEMBL4592533	KI	0.61 nM
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]-2-methylbenzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.61 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-ethyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonyl}-S-alaninate hydrochloride	IC50	0.63 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
CHEMBL4435567	KI	0.66 nM
CHEMBL4443353	KI	0.66 nM
Methyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate	IC50	0.68 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.68 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
4-hydroxy-3-{[(3S)-2-oxo-3-{thieno[3,2-b]pyridine-2-sulfonamido}pyrrolidin-1-yl]methyl}benzene-1-carboximidamide	KI	0.7 nM
4-[3-(3-Benzyl-5-carbamimidoyl-1H-indol-2-yl)-5-bromo-4-hydroxy-phenyl]-butyric acid	KI	0.7 nM
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N,N’-dimethyl-guanidinomethyl)-benzoylamino]-benzamide	IC50	0.7 nM
N-(2-(5-chloropyridin-2-ylcarbamoyl)-4-methoxyphenyl)-4-(N,N-dimethylcarbamimidoyl)-2-fluorobenzamide	IC50	0.7 nM
CHEMBL4436082	IC50	0.7 nM
4-{4-[3-(5-Carbamimidoyl-2-hydroxy-phenyl)-allylcarbamoyl]-phenyl}-pyridine-2-carboxylic acid amide	KI	0.75 nM
Methyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate	IC50	0.76 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
(S)-N-Benzo[1,3]dioxol-5-ylmethyl-4-cyclohexyl-3-{2-[((R)-4-guanidino-2-phenylmethanesulfonylamino-butyryl)-methyl-amino]-acetylamino}-2-oxo-butyramide	IC50	0.78 nM
2-[4-(5-Chloro-naphthalene-2-sulfonyl)-2-oxo-piperazin-1-yl]-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide	IC50	0.79 nM
3-(1-Methyl-1H-imidazol-2-yl)propyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate	IC50	0.79 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
{4-[4-Chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-phenylcarbamoyl]-benzyl}-trimethyl-ammonium	IC50	0.8 nM
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N,N’,N’’-trimethyl-guanidinomethyl)-benzoylamino]-benzamide	IC50	0.8 nM
CHEMBL4541084	IC50	0.8 nM
CHEMBL5557468	KI	0.81 nM
(R)-N-[((S)-1-Carbamimidoyl-2-hydroxy-piperidin-3-ylcarbamoyl)-methyl]-3-(1-carbamimidoyl-piperidin-4-yl)-2-phenylmethanesulfonylamino-propionamide; TFA	IC50	0.83 nM
Peptide boronate	KI	0.848 nM

ChEMBL bioactivities

820 potent at pChembl≥5 of 1139 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL2448441
10.46	IC50	0.035	nM	CHEMBL505190
10.39	Ki	0.041	nM	CHEMBL4569923
10.29	Ki	0.051	nM	CHEMBL4439523
10.22	IC50	0.06	nM	CHEMBL502293
10.15	Ki	0.07	nM	CHEMBL4476141
10.15	IC50	0.07	nM	CHEMBL520364
9.90	IC50	0.127	nM	CHEMBL484615
9.89	Ki	0.13	nM	CHEMBL4458743
9.85	Ki	0.14	nM	CHEMBL4588827
9.82	Ki	0.15	nM	CHEMBL4458743
9.79	IC50	0.163	nM	CHEMBL505455
9.70	Ki	0.2	nM	CHEMBL2315243
9.68	Ki	0.21	nM	CHEMBL4454304
9.64	IC50	0.229	nM	CHEMBL507020
9.64	IC50	0.23	nM	CHEMBL105819
9.62	IC50	0.242	nM	CHEMBL451066
9.60	Ki	0.25	nM	CHEMBL3660186
9.60	IC50	0.252	nM	CHEMBL506771
9.51	IC50	0.308	nM	CHEMBL505720
9.49	IC50	0.32	nM	CHEMBL4576519
9.49	Ki	0.32	nM	CHEMBL4454130
9.45	IC50	0.358	nM	CHEMBL507281
9.40	Ki	0.4	nM	CHEMBL3660191
9.40	IC50	0.4	nM	CHEMBL4456691
9.40	IC50	0.4	nM	CHEMBL4436082
9.39	IC50	0.408	nM	CHEMBL499632
9.38	IC50	0.42	nM	CHEMBL4447001
9.38	Ki	0.42	nM	CHEMBL4454130
9.37	Ki	0.43	nM	CHEMBL4553652
9.35	Ki	0.45	nM	CHEMBL4579797
9.35	Ki	0.45	nM	CHEMBL4591922
9.34	IC50	0.457	nM	CHEMBL507279
9.32	Ki	0.48	nM	CHEMBL4462811
9.31	IC50	0.494	nM	CHEMBL524548
9.29	Ki	0.51	nM	CHEMBL4571212
9.28	Ki	0.52	nM	CHEMBL2315236
9.28	Ki	0.52	nM	CHEMBL4553652
9.27	Ki	0.54	nM	CHEMBL4560508
9.26	Ki	0.55	nM	CHEMBL3666821
9.26	IC50	0.554	nM	CHEMBL524370
9.25	Ki	0.56	nM	CHEMBL4560508
9.24	Ki	0.57	nM	CHEMBL2315246
9.22	Ki	0.6	nM	CHEMBL3660185
9.22	Ki	0.6	nM	CHEMBL3660182
9.22	Ki	0.6	nM	CHEMBL3660174
9.21	Ki	0.61	nM	CHEMBL4592533
9.18	Ki	0.66	nM	CHEMBL4435567
9.18	Ki	0.66	nM	CHEMBL4443353
9.18	IC50	0.656	nM	CHEMBL524732

PubChem BioAssay actives

866 with measured affinity, of 2402 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-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4-[(2S)-butan-2-yl]-19,34-bis[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-28-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-thiophen-3-ylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	<0.0001	uM
benzyl N-[(2S)-1-[(2S)-2-[[5-hydrazinyl-5-sulfanylidene-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate;hydrobromide	157974: Binding affinity against plasmin	ki	<0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-19,25-bis(4-aminobutyl)-49-benzyl-4-[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-28-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0001	uM
(19S,22R)-N-[(4-carbamimidoylphenyl)methyl]-22-(cyclohexylsulfamoylamino)-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaene-19-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626133: Binding affinity to human plasmin assessed as slow binding constant in presence of Mes-DArg-Phe-Arg-AMC after 20 mins by Dixon plot analysis	ki	0.0001	uM
(19S,22R)-22-(benzenesulfonamido)-N-[(4-carbamimidoylphenyl)methyl]-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaene-19-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626135: Inhibition of human plasmin using Mes-DSer(Bzl)-Phe-Arg-AMC as substrate by Dixon plot analysis	ki	0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-28-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-prop-1-ynylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[4-(hydroxymethyl)thiophen-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-prop-1-en-2-ylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4-[(2S)-butan-2-yl]-34-[4-(diaminomethylideneamino)butyl]-19-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-28-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0002	uM
2-[4-[4-(aminomethyl)thiophen-3-yl]-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0002	uM
(2S)-2-[[(2S)-2-[4-(diaminomethylideneamino)butanoylamino]-3-(4-nitrophenyl)propanoyl]-methylamino]-3-hydroxy-N-[(1R)-1-phenylethyl]butanamide	157803: Concentration required to inhibit Plasmin was determined	ic50	0.0002	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(furan-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0002	uM
2-[4-[4-(azidomethyl)thiophen-3-yl]-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0002	uM
(19S,22R)-22-(benzylsulfonylamino)-N-[(4-carbamimidoylphenyl)methyl]-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaene-19-carboxamide;2,2,2-trifluoroacetic acid	724901: Inhibition of human plasmin protease domain using Tos-Gly-Pro-Lys-pNA as substrate by micro plate reader analysis	ki	0.0002	uM
4-[4-[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-[(4-chloro-1H-indazol-6-yl)amino]-3-oxopropyl]phenyl]-3-methyl-N-propan-2-ylbenzamide	1558626: Inhibition of human plasmin preincubated for 15 mins followed by MeOSuc-Ala-Phe-Lys-AMC substrate addition and measured after 30 mins by fluorescence method	ic50	0.0003	uM
(17S,20R)-N-[(4-carbamimidoylphenyl)methyl]-20-(cyclohexylsulfamoylamino)-3,10,19-trioxo-2,5,8,11,18-pentazatetracyclo[20.2.2.25,8.212,15]triaconta-1(25),12,14,22(26),23,27-hexaene-17-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626135: Inhibition of human plasmin using Mes-DSer(Bzl)-Phe-Arg-AMC as substrate by Dixon plot analysis	ki	0.0003	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(furan-3-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0003	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(3-methylbut-2-enyl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0003	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxo-4-piperidin-4-ylbutan-2-yl]-5-phenylpentanamide	1558652: Inhibition of human plasmin using tosyl-Gly-Pro-Lys-pNA as substrate	ki	0.0003	uM
4-(aminomethyl)-N-[(2S)-1-[(7-chloro-2-oxo-1,3-dihydrobenzimidazol-5-yl)amino]-3-[4-(2-cyclopropyl-6-methyl-1H-benzimidazol-5-yl)phenyl]-1-oxopropan-2-yl]cyclohexane-1-carboxamide	1558626: Inhibition of human plasmin preincubated for 15 mins followed by MeOSuc-Ala-Phe-Lys-AMC substrate addition and measured after 30 mins by fluorescence method	ic50	0.0004	uM
3-[3-[4-[[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-[4-(5-methyl-2-propan-2-yl-1H-imidazo[4,5-b]pyridin-6-yl)phenyl]propanoyl]amino]phenyl]-1H-1,2,4-triazol-5-yl]-2,2,3,3-tetrafluoropropanoic acid	1558626: Inhibition of human plasmin preincubated for 15 mins followed by MeOSuc-Ala-Phe-Lys-AMC substrate addition and measured after 30 mins by fluorescence method	ic50	0.0004	uM
(19S,22R)-N-[[4-(aminomethyl)phenyl]methyl]-22-(cyclohexylsulfamoylamino)-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaene-19-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626133: Binding affinity to human plasmin assessed as slow binding constant in presence of Mes-DArg-Phe-Arg-AMC after 20 mins by Dixon plot analysis	ki	0.0004	uM
4-(aminomethyl)-N-[(2S)-1-[(7-chloro-2-oxo-1,3-dihydrobenzimidazol-5-yl)amino]-3-[4-(2-cyclopropyl-5-methyl-1H-imidazo[4,5-b]pyridin-6-yl)phenyl]-1-oxopropan-2-yl]cyclohexane-1-carboxamide	1558626: Inhibition of human plasmin preincubated for 15 mins followed by MeOSuc-Ala-Phe-Lys-AMC substrate addition and measured after 30 mins by fluorescence method	ic50	0.0004	uM
2-[(1R,4S,7S,13S,22S,25S,28S,31S,34R,37S,43S,46S,52S)-28-(4-aminobutyl)-52-benzyl-4-[(2S)-butan-2-yl]-19-(4-carbamimidamidobutyl)-22,37-bis(3-carbamimidamidopropyl)-25-(hydroxymethyl)-31-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,45,51,54-pentadecaoxo-56,57-dithia-2,5,11,17,20,23,26,29,32,35,38,41,44,50,53-pentadecazapentacyclo[32.20.4.07,11.013,17.046,50]octapentacontan-43-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0004	uM
(19S,22R)-22-(butylsulfonylamino)-N-[(4-carbamimidoylphenyl)methyl]-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaene-19-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626135: Inhibition of human plasmin using Mes-DSer(Bzl)-Phe-Arg-AMC as substrate by Dixon plot analysis	ki	0.0004	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[2-(hydroxymethyl)thiophen-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0004	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(4-hydroxybut-1-en-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0004	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxo-4-pyridin-4-ylbutan-2-yl]-5-phenylpentanamide	1558645: Inhibition of human plasmin using tosyl-Gly-Pro-Lys-pNA as substrate after 10 mins by UV/Vis photometry	ki	0.0005	uM
(19S,22R)-N-[[4-(aminomethyl)phenyl]methyl]-22-(benzenesulfonamido)-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaene-19-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626133: Binding affinity to human plasmin assessed as slow binding constant in presence of Mes-DArg-Phe-Arg-AMC after 20 mins by Dixon plot analysis	ki	0.0005	uM
(17S,20R)-20-(benzenesulfonamido)-N-[(4-carbamimidoylphenyl)methyl]-3,10,19-trioxo-2,5,8,11,18-pentazatetracyclo[20.2.2.25,8.212,15]triaconta-1(25),12,14,22(26),23,27-hexaene-17-carboxamide;tris(2,2,2-trifluoroacetic acid)	1626135: Inhibition of human plasmin using Mes-DSer(Bzl)-Phe-Arg-AMC as substrate by Dixon plot analysis	ki	0.0005	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(1,3-thiazol-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0005	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[2-(hydroxymethyl)furan-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0005	uM
(18R,21S)-18-(benzylsulfonylamino)-N-[(4-carbamimidoylphenyl)methyl]-3,10,19-trioxo-2,5,8,11,20-pentazatetracyclo[21.2.2.25,8.213,16]hentriaconta-1(26),13(29),14,16(28),23(27),24-hexaene-21-carboxamide;2,2,2-trifluoroacetic acid	724901: Inhibition of human plasmin protease domain using Tos-Gly-Pro-Lys-pNA as substrate by micro plate reader analysis	ki	0.0005	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-19,25-bis(4-aminobutyl)-28,49-dibenzyl-4-[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0006	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[4-(hydroxymethyl)furan-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0006	uM
(2S)-2-[[(2R)-2-(benzylsulfonylamino)-4-[1-(cyclopropanecarbonyl)piperidin-4-yl]butanoyl]amino]-N-[(4-carbamimidoylphenyl)methyl]-4-piperidin-4-ylbutanamide	1558652: Inhibition of human plasmin using tosyl-Gly-Pro-Lys-pNA as substrate	ki	0.0006	uM
(10S,13R)-13-(benzylsulfonylamino)-N-[(4-carbamimidoylphenyl)methyl]-3,12,20-trioxo-1,4,11,19,22-pentazatetracyclo[20.3.2.25,8.215,18]hentriaconta-5,7,15(29),16,18(28),30-hexaene-10-carboxamide;2,2,2-trifluoroacetic acid	724901: Inhibition of human plasmin protease domain using Tos-Gly-Pro-Lys-pNA as substrate by micro plate reader analysis	ki	0.0006	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-19,25-bis(4-aminobutyl)-49-benzyl-4-[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-28-(1H-indol-3-ylmethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0007	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-19,25-bis(4-aminobutyl)-4-(2-amino-2-oxoethyl)-49-benzyl-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-28-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1574053: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate after 30 mins	ki	0.0007	uM
2-[4-benzyl-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0007	uM
2-[4-[(Z)-but-2-enyl]-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0007	uM
(17S,20R)-20-(benzylsulfonylamino)-N-[(4-carbamimidoylphenyl)methyl]-3,10,19-trioxo-2,5,8,11,18-pentazatetracyclo[20.2.2.25,8.212,15]triaconta-1(25),12,14,22(26),23,27-hexaene-17-carboxamide;2,2,2-trifluoroacetic acid	724901: Inhibition of human plasmin protease domain using Tos-Gly-Pro-Lys-pNA as substrate by micro plate reader analysis	ki	0.0007	uM
5-[4-[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-[(7-chloro-2-oxo-3H-1,3-benzoxazol-5-yl)amino]-3-oxopropyl]phenyl]-6-methyl-N-propan-2-ylpyridine-2-carboxamide	1558626: Inhibition of human plasmin preincubated for 15 mins followed by MeOSuc-Ala-Phe-Lys-AMC substrate addition and measured after 30 mins by fluorescence method	ic50	0.0008	uM
methyl N-[(19S,22R)-19-[(4-carbamimidoylphenyl)methylcarbamoyl]-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaen-22-yl]carbamate;tris(2,2,2-trifluoroacetic acid)	1626133: Binding affinity to human plasmin assessed as slow binding constant in presence of Mes-DArg-Phe-Arg-AMC after 20 mins by Dixon plot analysis	ki	0.0008	uM
benzyl N-[(19S,22R)-19-[(4-carbamimidoylphenyl)methylcarbamoyl]-3,12,21-trioxo-2,6,9,13,20-pentazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(27),14(30),15,17(29),24(28),25-hexaen-22-yl]carbamate;tris(2,2,2-trifluoroacetic acid)	1626135: Inhibition of human plasmin using Mes-DSer(Bzl)-Phe-Arg-AMC as substrate by Dixon plot analysis	ki	0.0008	uM
3-[[(2R)-1-[[(2S)-3-(3-carbamimidoylphenyl)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxopropan-2-yl]amino]-1-oxo-5-phenylpentan-2-yl]sulfamoylmethyl]benzoic acid	2064597: Binding affinity to plasmin (unknown origin) assessed as inhibition constant	ki	0.0008	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(3-hydroxyprop-1-en-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397860: Inhibition of plasmin	ic50	0.0008	uM
(8S,11R)-11-(benzylsulfonylamino)-N-[(4-carbamimidoylphenyl)methyl]-10-oxo-3,4,5,9,14,15,16-heptazatetracyclo[16.3.1.13,6.113,16]tetracosa-1(21),4,6(24),13(23),14,18(22),19-heptaene-8-carboxamide	656100: Inhibition of plasmin by dixon plot method	ki	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethinyl Estradiol	affects binding, increases expression, affects cotreatment, increases activity	5
Benzo(a)pyrene	decreases expression, increases methylation	3
Contraceptives, Oral	increases expression	3
Gestodene	increases expression, affects cotreatment, increases activity	2
ethinyl estradiol-desogestrel combination	increases activity, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation, affects expression	2
Levonorgestrel	affects cotreatment, increases expression	2
ginger extract	decreases expression, increases abundance	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
norgestimate	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	increases expression	1
entinostat	decreases expression	1
belinostat	decreases expression	1
(R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine	decreases activity, decreases reaction, increases activity, increases secretion, affects reaction	1
NuvaRing	increases expression	1
(+)-JQ1 compound	decreases expression	1
waixenicin A	increases activity, increases secretion	1
Arsenic Trioxide	decreases activity	1
Vorinostat	decreases expression	1
Amiloride	decreases reaction, increases degradation	1
Arsenic	decreases activity, decreases reaction, increases reaction	1

ChEMBL screening assays

480 unique, capped per target: 467 binding, 7 admet, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003517	Binding	Inhibition of plasmin after 30 mins by microtiter plate method	Micropeptins 478-A and -B, Plasmin Inhibitors from the Cyanobacterium Microcystis aeruginosa — *J Nat Prod*
CHEMBL3739099	ADMET	Stability of the compound assessed as Plasmin (unknown origin)-mediated drug degradation after 1 hr	Design of Specific Serine Protease Inhibitors Based on a Versatile Peptide Scaffold: Conversion of a Urokinase Inhibitor to a Plasma Kallikrein Inhibitor. — *J Med Chem*
CHEMBL762810	Functional	Time to reach maximum percent inhibition by the compound was determined against plasmin(625 nM)	Guanidinophenyl-substituted enol lactones as selective, mechanism-based inhibitors of trypsin-like serine proteases. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 294 trials:

NCT	Phase	Status	Title
NCT00914966	Phase 4	COMPLETED	A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
NCT01151735	Phase 4	WITHDRAWN	C1-INH Compared to Placebo at the Time of Prodromal Symptoms for Hereditary Angioedema (HAE) Exacerbation
NCT01457430	Phase 4	COMPLETED	Efficacy, Safety and Tolerability of Icatibant for the Treatment of HAE
NCT01679912	Phase 4	COMPLETED	A Call Center During HAE Attacks (SOS HAE)
NCT06690047	Phase 4	COMPLETED	Treatment of Hereditary Angioedema Prodrome with Recombinant C1-esterase Inhibitor (Ruconest)
NCT06806657	Phase 4	COMPLETED	Safety Study in Subjects ≥ 12 Years of Age With Hereditary Angioedema Switching to Garadacimab
NCT07290855	Phase 4	COMPLETED	A Study to Evaluate the Safety and Efficacy of Icatibant in Patients With Bradykinin Induced Angioedema
NCT07654829	Phase 4	RECRUITING	Safety and Effectiveness of Sebetralstat (KVD900) for Short-Term Prophylaxis Before Procedures in People With Hereditary Angioedema (KONTROL)
NCT00157690	Phase 4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	Phase 4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	Phase 4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	Phase 4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	Phase 4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	Phase 4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	Phase 4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	Phase 4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	Phase 4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	Phase 4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	Phase 4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	Phase 4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	Phase 4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	Phase 4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	Phase 4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	Phase 4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	Phase 4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	Phase 4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	Phase 4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	Phase 4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	Phase 4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	Phase 4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	Phase 4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	Phase 4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	Phase 4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	Phase 4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	Phase 4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	Phase 4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	Phase 4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	Phase 4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	Phase 4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	Phase 4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	Phase 4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	Phase 4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	Phase 4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	Phase 4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	Phase 4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	Phase 4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	Phase 4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	Phase 4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis
NCT02178540	Phase 4	COMPLETED	Study to Validate the Instructions for Use of TOBI® Podhaler™ in Cystic Fibrosis Patients
NCT02277626	Phase 4	COMPLETED	Electro Flo 5000 and Vest Therapy
NCT02421120	Phase 4	COMPLETED	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients
NCT02444234	Phase 4	COMPLETED	Pharmacokinetics of Tedizolid Phosphate in Cystic Fibrosis
NCT02504827	Phase 4	COMPLETED	Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis
NCT02547116	Phase 4	WITHDRAWN	Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
NCT02677701	Phase 4	COMPLETED	Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
NCT02700282	Phase 4	COMPLETED	Backpack Carrying in Children With Cystic Fibrosis
NCT02823470	Phase 4	TERMINATED	A Pilot Study to Evaluate the Use of Smart Adherence Technology to Measure Lumacaftor/Ivacaftor Adherence in CF Subjects Homozygous for the F508del CFTR Mutation
NCT02823964	Phase 4	COMPLETED	EASY: Extended Access to Sollpura Over Years
NCT02875366	Phase 4	COMPLETED	A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
NCT02894684	Phase 4	COMPLETED	Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLG across ~30M SureChEMBL compounds — explore on Sugi Predict.