KLK1

Summary

KLK1 (kallikrein 1, HGNC:6357) is a protein-coding gene on chromosome 19q13.33, encoding Kallikrein-1 (P06870). Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen.

Source: NCBI Gene 3816 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary arterial hypertension (Limited, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 79 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002257

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6357
Approved symbol	KLK1
Name	kallikrein 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	Klk6
Ensembl gene	ENSG00000167748
Ensembl biotype	protein_coding
OMIM	147910
Entrez	3816

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000301420, ENST00000593325, ENST00000593859, ENST00000596300, ENST00000878924

RefSeq mRNA: 1 — MANE Select: NM_002257 NM_002257

CCDS: CCDS12804

Canonical transcript exons

ENST00000301420 — 5 exons

Exon	Start	End
ENSE00003099088	50819146	50819349
ENSE00003494840	50823703	50823787
ENSE00003500358	50821712	50821871
ENSE00003581061	50819899	50820035
ENSE00003609858	50820154	50820443

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 99.87.

FANTOM5 (CAGE): breadth broad, TPM avg 23.1662 / max 14215.8780, expressed in 410 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182284	18.0672	35
182279	2.9905	244
182281	0.7226	199
182278	0.6631	129
182280	0.3418	95
182282	0.1724	6
182276	0.1112	53
182277	0.0618	27
182283	0.0356	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.87	gold quality
pancreas	UBERON:0001264	97.62	gold quality
mucosa of transverse colon	UBERON:0004991	97.30	gold quality
parotid gland	UBERON:0001831	97.20	gold quality
rectum	UBERON:0001052	96.43	gold quality
skin of abdomen	UBERON:0001416	95.47	gold quality
islet of Langerhans	UBERON:0000006	95.02	gold quality
skin of leg	UBERON:0001511	94.92	gold quality
type B pancreatic cell	CL:0000169	94.55	gold quality
zone of skin	UBERON:0000014	92.52	gold quality
upper arm skin	UBERON:0004263	90.59	silver quality
transverse colon	UBERON:0001157	90.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.96	gold quality
adult mammalian kidney	UBERON:0000082	89.78	gold quality
ileal mucosa	UBERON:0000331	88.79	gold quality
epithelial cell of pancreas	CL:0000083	88.50	silver quality
small intestine Peyer’s patch	UBERON:0003454	88.41	gold quality
saliva-secreting gland	UBERON:0001044	87.42	gold quality
olfactory bulb	UBERON:0002264	86.88	gold quality
small intestine	UBERON:0002108	86.44	gold quality
triceps brachii	UBERON:0001509	86.25	gold quality
tongue squamous epithelium	UBERON:0006919	85.77	gold quality
gluteal muscle	UBERON:0002000	85.34	gold quality
lower esophagus mucosa	UBERON:0035834	84.69	gold quality
minor salivary gland	UBERON:0001830	84.43	gold quality
spleen	UBERON:0002106	83.92	gold quality
colonic mucosa	UBERON:0000317	83.59	gold quality
kidney	UBERON:0002113	83.56	gold quality
nephron tubule	UBERON:0001231	83.53	gold quality
diaphragm	UBERON:0001103	83.49	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	2219.10
E-GEOD-81547	yes	1413.23
E-MTAB-5061	yes	20.55
E-MTAB-8410	yes	19.39
E-ENAD-27	yes	6.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, GATA3, NFIA, SP1

Literature-anchored findings (GeneRIF, showing 40)

• Tissue kallikrein KLK1 is expressed de novo in endothelial cells and mediates relaxation of human umbilical veins. (PMID:11727832)
• Association of the tissue kallikrein gene promoter with ESRD and hypertension. (PMID:11849458)
• Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. (PMID:11912256)
• Kinetic peculiarities of human tissue kallikrein (PMID:11913965)
• endothelial cells synthesize and release an active form of tissue kallikrein - kinin generation on the surface may play an important role in maintenance of circulation homeostasis (PMID:12581867)
• Diminution of kallikrein biosynthesis in African Americans seems to involve mechanisms at or distal to the aldosterone receptor, and perhaps at the level of the kallikrein gene itself. (PMID:12670744)
• essentially unsusceptible to processing by human urinary kallikrein (tissue-type) (PMID:12887060)
• that in the airways, monocytes, neutrophils, and alveolar macrophages may contribute to increased TK activity (PMID:14660481)
• Sustained hyaluronan depolymerization is expected to cause tissue kallikrein activation, EGF release, and EGFR signaling. (PMID:14988406)
• The K allele of KLK1 promoter and TT genotype of TGF-beta1 may be a genetic KLK1 -130 GN and -128 G-C, and the susceptibility factor contributing to progressive renal deterioration in Taiwanese primary vesicoureteric reflux children. (PMID:15086490)
• Transduced human tissue kallikrein activated murine Akt-B through Ser-473 phosphorylation providing new information on the pathway involved in hTK-induced neoangiogenesis. (PMID:15364809)
• transgenic rats expressing hKLK1 have an impaired renal response to acute volume expansion (PMID:15544850)
• kallikrein/kinin protects against cardiomyocyte apoptosis in vivo and in vitro via Akt-Bad.14-3-3 and Akt-GSK-3beta-caspase-3 signaling pathways (PMID:15611141)
• analysis of peptide inhibitor/substrate binding to human apo kallikrein 1 (PMID:15651049)
• Induction of KLK1 in carotid arteriosclerosis does not lead to kallikrein-kinins pathway activation. (PMID:15662224)
• Data describe the vascular, hormonal, and renal phenotypes of carriers of the loss-of-function polymorphism of the human tissue kallikrein gene. (PMID:15765151)
• Gene delivery protects against rat diabetic cardiomyopathy by improving cardiac function and promoting glucose utilization and lipid metabo (PMID:15855348)
• There are polymorphisms in regulatory region of human tissue kallikrein gene in Chinese Han people. Differences in both allele and genotype frequencies show association of hypertension with polymorphisms. (PMID:15905889)
• the the kallikrein-kinin system has roles in intramyocardial inflammation, endothelial dysfunction and oxidative stress in diabetic cardiomyopathy (PMID:16129698)
• findings suggest the presence of an abnormality in the kallikrein-kinin system in the placentas of women with pregnancy-induced hypertension (PMID:17050061)
• KLK1 may participate in epidermal desquamation through cleavage of desmoglein 1 and regulation by lympho-epithelial Kazal-type-related inhibitor (LEKTI). (PMID:17158887)
• Up-Regulation of kallikrein 11 is associated with ovarian carcinoma (PMID:17671125)
• tissue kallikrein may act as an intrarenal modulator of Ca reabsorption (PMID:17699431)
• rs5517 in the KLK1 gene was significantly associated with essential hypertension in a Chinese Han population (PMID:17762646)
• Kallikrein 6 induces E-cadherin shedding and promotes cell proliferation, migration, and invasion. (PMID:17804733)
• Protective actions of human tissue kallikrein gene in transgenic rat hearts. (PMID:18182238)
• Proteins such as caveolin-1 (CAV-1) and Akt, Proto-Oncogene Protein, which are known to be altered in colon cancer, affect KLK6 expression and KLK6 secretion (PMID:18283336)
• pTK levels are genetically determined and regulated by Na and K diet (PMID:18327081)
• KLK1 was shown to exhibit both trypsin- and chymotrypsin-like selectivities with Tyr/Arg preferred at site P1, Ser/Arg strongly preferred at P1’, and Phe/Leu at P2. (PMID:18359858)
• restoration of the kallikrein-kinin system reduces kidney injury and protects renal function in 5/6-nephrectomized rats via changes in the expression and activation of G protein-coupled receptors including B(2)R (PMID:18402547)
• The kallikrein-kinin system may be one of the more important players in angiogenesis associated with prostate and breast tumours. (PMID:18577888)
• role of KLK1 in arterial function; role of KLK1 in the control of ionic transport in the renal tubule; cardio- and nephro-protective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes [review] (PMID:18627303)
• Tissue kallikrein decreased GSK-3beta activity via the phosphatidylinositol 3-kinase-Akt pathway and enhanced VEGF and VEGFR-2 expression in endothelial cells. (PMID:18689794)
• extensive cytoplasmic expression of tissue prokallikrein and plasma prekallikrein was observed, which was similar in small cell and non-small cell lung tumours; however, nuclear labelling for the kallikreins was absent or limited (PMID:18713009)
• factor XII is activated by misfolded proteins in humans, leading to kallikrein formation without initiating coagulation (PMID:18725990)
• S(1)’ and S(2)’ subsite specificity of KLK1 showed peculiarities that were observed with substrates containing the amino acid sequence of human kininogen (PMID:18844446)
• GATA3 was found to bind the site located at -954/-855 and to be a key regulator of abundant KLK1 expression in keratinocyte. (PMID:19232384)
• Combination of KLK2, 3, 13, and 14 and KLK1, 2, 5, 6, 7, 8, 10, 13, and 14 showed very strong discriminatory potential for semen liquefaction and viscosity, respectively. (PMID:19558318)
• Angiogenesis in cervical cancer is mediated by HeLa metabolites through endothelial cell tissue kallikrein. (PMID:19578768)
• elevated plasma levels in patients with hereditary angioedema (PMID:20143645)

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klk1b16	ENSMUSG00000038968
mus_musculus	Klk1b11	ENSMUSG00000044485
mus_musculus	Klk1b26	ENSMUSG00000053719
mus_musculus	Klk1b9	ENSMUSG00000059042
mus_musculus	Klk1b22	ENSMUSG00000060177
mus_musculus	Klk1b8	ENSMUSG00000063089
mus_musculus	Klk1b1	ENSMUSG00000063133
mus_musculus	Klk1b27	ENSMUSG00000063177
mus_musculus	Klk1b24	ENSMUSG00000063713
mus_musculus	Klk1	ENSMUSG00000063903
mus_musculus	Klk1b5	ENSMUSG00000066512
mus_musculus	Klk1b4	ENSMUSG00000066513
mus_musculus	Klk1b3	ENSMUSG00000066515
mus_musculus	Klk1b21	ENSMUSG00000066516
drosophila_melanogaster	CG9673	FBGN0030775
drosophila_melanogaster	CG4477	FBGN0035971
drosophila_melanogaster	CG17404	FBGN0038001
drosophila_melanogaster	CG12256	FBGN0038002
drosophila_melanogaster	CG3916	FBGN0038003
drosophila_melanogaster	CG17477	FBGN0038479
drosophila_melanogaster	CG4053	FBGN0038482
drosophila_melanogaster	CG31269	FBGN0051269
drosophila_melanogaster	CG32808	FBGN0052808
drosophila_melanogaster	Phae2	FBGN0263235
drosophila_melanogaster	Send2	FBGN0264253

Paralogs (12): PRSS54 (ENSG00000103023), KLK14 (ENSG00000129437), KLK8 (ENSG00000129455), TMPRSS4 (ENSG00000137648), KLK3 (ENSG00000142515), KLK4 (ENSG00000167749), KLK2 (ENSG00000167751), KLK5 (ENSG00000167754), KLK11 (ENSG00000167757), KLK7 (ENSG00000169035), KLK12 (ENSG00000186474), PRSS58 (ENSG00000258223)

Protein

Protein identifiers

Kallikrein-1 — P06870 (reviewed: P06870)

Alternative names: Kidney/pancreas/salivary gland kallikrein, Tissue kallikrein

All UniProt accessions (3): A0A1R3UCD2, P06870, M0R318

UniProt curated annotations — full annotation on UniProt →

Function. Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. (Microbial infection) Cleaves Neisseria meningitidis NHBA in saliva; Neisseria is an obligate commensal of the nasopharyngeal mucosa.

Tissue specificity. Isoform 2 is expressed in pancreas, salivary glands, kidney, colon, prostate gland, testis, spleen and the colon adenocarcinoma cell line T84.

Post-translational modifications. The O-linked polysaccharides on Ser-93, Ser-104 and Ser-167 are probably the mucin type linked to GalNAc. In PubMed:3163150, GalNAc was detected with the corresponding peptides but not located.

Polymorphism. Genetic variations in KLK1 are the cause of a decreased in urinary kallikrein activity [MIM:615953]. The His-77 mutation dramatically reduces the activity of the enzyme in the urine. There is a 50 to 60% reduction in urinary kallikrein activity in His-77 individuals, but renal and hormonal adaptation to dietary changes in sodium and potassium are unaffected. However, in studies of brachial artery function, His-77 individuals consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared to Arg-77 individuals. This partial genetic deficiency in kallikrein activity is associated with a form of arterial dysfunction involving inappropriate inward remodeling of the brachial artery despite a chronic increase in shear stress.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P06870-1	1	yes
P06870-2	2

RefSeq proteins (1): NP_002248* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.35 — tissue kallikrein (BRENDA: 12 organisms, 294 substrates, 207 inhibitors, 205 Km, 182 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
DL-VAL-LEU-ARG-P-NITROANILIDE	0.12–58.8	6
PRO-PHE-ARG-4-METHYLCOUMARIN 7-AMIDE	0.07–0.114	5
N-ALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.08–0.333	4
N-ALPHA-TOSYL-L-ARGININE METHYL ESTER	0.022–0.117	4
SUCCINYL-VAL-PRO-PHE-THIOBENZYL ESTER	0.516–0.842	4
D-PRO-PHE-ARG-4-METHYLCOUMARIN-7-AMIDE	0.0002–0.0031	3
D-PRO-PHE-PHE-4-METHYLCOUMARIN-7-AMIDE	0.001–0.07	3
D-VAL-LEU-ARG-P-NITROANILIDE	0.0183–28.4	3
O-AMINOBENZOYL-GFSPFRSVTVQ-ETHYLENEDIAMINE 2,4-D	0.0002–0.0025	3
O-AMINOBENZOYL-MTEMARRPQ-ETHYLENEDIAMINE 2,4-DIN	0.003–0.0073	3
ABZ-KLRSSQ-EDDNP	0.0006	2
ACETYL-ALA-ARG METHYL ESTER	0.6–1.14	2
ACETYL-PHE-ARG METHYL ESTER	0.0244–0.0311	2
O-AMINOBENZOYL-FRSSR-N-(2,4-DINITROPHENYL)ETHYLE	0.0002–0.0006	2
O-AMINOBENZOYL-FRSVQ-N-(2,4-DINITROPHENYL)ETHYLE	0.0009–0.0073	2

UniProt features (48 total): strand 16, glycosylation site 6, disulfide bond 5, helix 5, sequence variant 4, sequence conflict 3, active site 3, signal peptide 1, propeptide 1, splice variant 1, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1SPJ	X-RAY DIFFRACTION	1.7
8YGY	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06870-F1	91.84	0.86

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 (3): 65 (charge relay system); 120 (charge relay system); 214 (charge relay system)

Disulfide bonds (5): 31–174, 50–66, 153–220, 185–199, 210–235

Glycosylation sites (6): 108, 165, 167, 93, 102, 104

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-1266738	Developmental Biology
R-HSA-392499	Metabolism of proteins
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 232 (showing top): MODULE_172, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GOBP_GROWTH, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_REGENERATION

GO Biological Process (3): regulation of systemic arterial blood pressure (GO:0003073), zymogen activation (GO:0031638), proteolysis (GO:0006508)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), secretory granule (GO:0030141), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of proteins	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of blood pressure	1
protein processing	1
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
endomembrane system	1
secretory vesicle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLK1	SERPINA4	P29622	997
KLK1	KNG1	P01042	935
KLK1	SERPINA5	P05154	784
KLK1	BDKRB2	P30411	687
KLK1	ACE	P12821	675
KLK1	SPINT1	O43278	656
KLK1	SLC14A2	Q15849	639
KLK1	IL4I1	Q96RQ9	590
KLK1	BDKRB1	P46663	568
KLK1	MUC16	Q8WXI7	547
KLK1	AGT	P01019	542
KLK1	APOC2	P02655	535
KLK1	CPB2	Q96IY4	533
KLK1	SPINT2	O43291	530
KLK1	SERPINA6	P08185	524

IntAct

6 interactions, top by confidence:

A	B	Type	Score
KLK1	CRLF1	psi-mi:“MI:0914”(association)	0.350
KLK1	SLC25A20	psi-mi:“MI:0914”(association)	0.350
KLK1	PPOX	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): SERPINA1 (Reconstituted Complex), A2M (Reconstituted Complex), ITIH4 (Reconstituted Complex), KNG1 (Reconstituted Complex), SERPINC1 (Reconstituted Complex), PROC (Reconstituted Complex), SERPINA4 (Reconstituted Complex), NSUN3 (Affinity Capture-MS), TAMM41 (Affinity Capture-MS), HIGD2A (Affinity Capture-MS), PTPMT1 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), UBA52 (Affinity Capture-MS), MUM1 (Affinity Capture-MS), PXMP2 (Affinity Capture-MS)

ESM2 similar proteins: O19023, O46644, P00752, P00758, P00764, P00767, P00770, P00774, P05208, P05805, P06870, P06872, P08217, P08218, P08419, P08861, P09093, P12323, P12788, P15946, P15948, P16049, P21812, P27435, P32821, P32822, P35034, P36373, P36374, P36376, P49864, P50340, P55091, P80931, Q02844, Q29461, Q29463, Q3SYP2, Q5R1M5, Q61759

Diamond homologs: A7WPL7, O35164, O35205, O46683, O60259, O88780, P00746, P00752, P00760, P00761, P00762, P00763, P00764, P00770, P00772, P00773, P04187, P06870, P06871, P07146, P07288, P08311, P08426, P08882, P08883, P08884, P09582, P09650, P10144, P11032, P11033, P11034, P12323, P12544, P12788, P13366, P15119, P16049, P17977, P18291

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1694 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50820148:ACAT:A	donor_loss	1.0000
19:50820150:ATAC:A	donor_loss	1.0000
19:50820151:TA:T	donor_loss	1.0000
19:50820152:A:AC	donor_gain	1.0000
19:50820152:AC:A	donor_loss	1.0000
19:50820153:C:CC	donor_gain	1.0000
19:50820153:CA:C	donor_gain	1.0000
19:50820153:CAA:C	donor_gain	1.0000
19:50820153:CAAT:C	donor_gain	1.0000
19:50820153:CAATT:C	donor_gain	1.0000
19:50820201:C:A	donor_gain	1.0000
19:50820207:T:TA	donor_gain	1.0000
19:50820439:AATTG:A	acceptor_gain	1.0000
19:50820441:TTG:T	acceptor_gain	1.0000
19:50820442:TG:T	acceptor_gain	1.0000
19:50820444:C:CC	acceptor_gain	1.0000
19:50822674:T:TA	donor_gain	1.0000
19:50959312:TCACC:T	acceptor_gain	1.0000
19:50959313:CACC:C	acceptor_gain	1.0000
19:50959313:CACCC:C	acceptor_gain	1.0000
19:50959314:ACC:A	acceptor_gain	1.0000
19:50959315:CC:C	acceptor_gain	1.0000
19:50959315:CCC:C	acceptor_gain	1.0000
19:50959316:CC:C	acceptor_gain	1.0000
19:50959316:CCTGC:C	acceptor_loss	1.0000
19:50959317:C:CC	acceptor_gain	1.0000
19:50959318:T:C	acceptor_loss	1.0000
19:50961881:C:CA	acceptor_loss	1.0000
19:50819895:TCA:T	donor_loss	0.9900
19:50819896:CACCA:C	donor_loss	0.9900

AlphaMissense

1729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50820176:C:A	W158C	1.000
19:50820176:C:G	W158C	1.000
19:50819224:C:A	W253C	0.999
19:50819224:C:G	W253C	0.999
19:50819345:T:A	D213V	0.999
19:50819936:C:G	C199S	0.999
19:50819937:A:T	C199S	0.999
19:50819226:A:G	W253R	0.998
19:50819226:A:T	W253R	0.998
19:50819340:C:A	G215W	0.998
19:50819345:T:G	D213A	0.998
19:50819346:C:G	D213H	0.998
19:50819936:C:T	C199Y	0.998
19:50819978:C:G	C185S	0.998
19:50819979:A:T	C185S	0.998
19:50820175:C:A	G159C	0.998
19:50820178:A:G	W158R	0.998
19:50820178:A:T	W158R	0.998
19:50820291:T:A	D120V	0.998
19:50820291:T:G	D120A	0.998
19:50821720:G:C	C66W	0.998
19:50821721:C:G	C66S	0.998
19:50821721:C:T	C66Y	0.998
19:50821722:A:T	C66S	0.998
19:50821741:C:A	W59C	0.998
19:50821741:C:G	W59C	0.998
19:50821743:A:G	W59R	0.998
19:50821743:A:T	W59R	0.998
19:50819293:C:A	W230C	0.997
19:50819293:C:G	W230C	0.997

dbSNP variants (sampled 300 via entrez): RS1000074745 (19:50820855 G>A), RS1000211094 (19:50820458 G>T), RS1000435465 (19:50820024 C>A), RS1000549668 (19:50825501 C>T), RS1000854107 (19:50825721 C>A,G), RS1001076315 (19:50822169 G>A), RS1001436730 (19:50821113 G>A,C,T), RS1001490448 (19:50821445 A>G), RS1002544194 (19:50822557 T>C,G), RS1003346358 (19:50823813 A>G), RS1003540862 (19:50823633 C>A,G,T), RS1004002971 (19:50823406 G>A), RS1004097113 (19:50822821 T>C,G), RS1004446268 (19:50824964 C>T), RS1004450317 (19:50822979 A>C,G)

Disease associations

OMIM: gene MIM:147910 | disease phenotypes: MIM:615953

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary arterial hypertension	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
pulmonary arterial hypertension	Limited	AD

Mondo (2): kallikrein, decreased urinary activity of (MONDO:0014415), pulmonary arterial hypertension (MONDO:0015924)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009268_6	Dental caries (decayed, missing and filled tooth surfaces)	3.000000e-06
GCST009731_13	Blood protein levels in cardiovascular risk	3.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010622	obsolete_kallikrein‐6 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C563653	Kallikrein, Decreased Urinary Activity of (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2319 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,621 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL273264	NAFAMOSTAT	3	7,063
CHEMBL85164	CAMOSTAT MESILATE	3	1,558

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

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

Ligand	Action	Affinity	Parameter
example 131 [WO2009133348]	Inhibition	9.27	pIC50

Binding affinities (BindingDB)

505 measured of 854 human assays (854 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl N-[(12R,14R)-14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-12,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.04 nM	US-10214512
4-[(2-{5-[5-chloro-2-(1H- tetrazol-1-yl)phenyl]-1- oxidopyridin-2-yl}-3- cyclopropylpropanoyl) amino]-2-fluorobenzoic acid	IC50	0.07 nM	US-9783530: Factor Xla inhibitors
methyl N-[(14R)-14-[5-[5-fluoro-2-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.08 nM	US-10214512
(S) 5-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)-2-(25-fluoro-4-oxo-3-aza-1(1,3),2(1,2)-dibenzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.09 nM	US-10214512
methyl N-[(12R,14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-12,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.09 nM	US-10214512
5-(5-Chloro-2-(1H-tetrazol-1-yl)phenyl)-2-(24-((methoxycarbonyl)amino)-4-oxo-3-aza-1(1,3),2(1,2) -dibenzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.1 nM	US-10214512
methyl N-[(10R,14R)-14-[5-(2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.1 nM	US-10214512
methyl N-[(14S)-14-[5-[5-chloro-2-(4-cyclopropyltriazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.11 nM	US-10214512
methyl N-[(14R)-14-[5-[2-fluoro-6-(trifluoromethyl)phenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.11 nM	US-10214512
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-5-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.12 nM	US-10214512
2-(25-carboxy-4-oxo-3-aza-1(1,3),2(1,2)-dibenzenacyclononaphane-9-yl)-5-(3-chloro-2-fluoro-6-(1H-tetrazol-1-yl)phenyl)pyridine 1-oxide	KI	0.13 nM	US-10214512
methyl N-[(14S)-14-[5-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.13 nM	US-10214512
methyl N-[14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-17-ethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.13 nM	US-10214512
methyl N-[(10R,14R)-14-[5-[6-(difluoromethoxy)-2,3-difluorophenyl]-1-oxidopyridin-1-ium-2-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.13 nM	US-10214512
4-{[(2R)-2-{5-[5-chloro-2- (1H-tetrazol-1-yl)phenyl]- 1-oxidopyridin-2-yl}-3- cyclopropylpropanoyl] amino}benzoic acid	IC50	0.14 nM	US-9783530: Factor Xla inhibitors
9-(5-(5-chloro-2-(1h-tetrazol-1-yl)phenyl)-1-oxidopyridin-2-yl)-15-fluoro-24-((methoxycarbonyl)amino)-4-oxo-3-aza-1(2,4)-pyridin-1-iuma -2(1,2)-benzenacyclononaphane 11-oxide	KI	0.14 nM	US-10214512
methyl N-[14-[5-[5-chloro-2-(difluoromethoxy)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
(14R)-5-amino-14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-17-methyl-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-9-one	KI	0.14 nM	US-10214512
methyl N-[(10R,14R)-17-cyclopropyl-14-[5-(2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
methyl N-[(10R,14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-ethyl-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.14 nM	US-10214512
(9R,13S)-13-[5-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-3-(difluoromethyl)-9-methyl-3,4,7-triazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	KI	0.14 nM	US-10214512
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-ethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.15 nM	US-10214512
methyl N-[(14R)-14-[5-[6-(difluoromethoxy)-2,3-difluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.15 nM	US-10214512
4-{[(2R)-2-{5-[5-chloro- 2-(1H-tetrazol-1- yl)phenyl]-1- oxidopyridin-2-yl}-3- phenylpropanoyl]amino} benzoic acid	IC50	0.16 nM	US-9783530: Factor Xla inhibitors
5-(3-chloro-2,6-difluorophenyl)-2-((5R,9S)-15-fluoro-24- ((methoxycarbonyl)amino)-5-methyl-4-oxo-3-aza-1(2,4)-pyridina-2(1,2)- benzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.16 nM	US-10214512
methyl N-[14-[5-[5-chloro-2-(trifluoromethoxy)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.17 nM	US-10214512
methyl N-[(10R,14R)-14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.17 nM	US-10214512
methyl N-[(10R,14R)-14-[5-[5-fluoro-2-(trifluoromethoxy)phenyl]-1-oxidopyridin-1-ium-2-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.17 nM	US-10214512
5-(5-Chloro-2-(1H-tetrazol-1-yl)phenyl)-2-((5R,9S)-25-fluoro-5-methyl-4-oxo-3-aza-1(1,3),2(1,2)-dibenzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.18 nM	US-10214512
5-amino-14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-9-one	KI	0.18 nM	US-10214512
4-[(2-{5-[3-chloro-2- fluoro-6-(1H-tetrazol-1- yl)phenyl]-1- oxidopyridin-2-yl}-3- cyclopropylpropanoyl) amino]benzoic acid	IC50	0.19 nM	US-9783530: Factor Xla inhibitors
methyl N-[(14S)-14-[5-[5-chloro-2-(4-cyanopyrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.19 nM	US-10214512
methyl N-[14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.19 nM	US-10214512
methyl N-[(14R)-14-[5-[3-chloro-6-(difluoromethyl)-2-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.2 nM	US-10214512
methyl N-[17-cyclopropyl-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.21 nM	US-10214512
13-[5-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-1-oxidopyridin-1-ium-2-yl]-3-(difluoromethyl)-3,4,7-triazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	KI	0.21 nM	US-10214512
(Z)-5-(5-Chloro-2-(1H-tetrazol-1-yl)phenyl)-2-(25-fluoro-4-oxo-11h-3-aza -1(4,2)-imidazola-2(1,2)-benzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.22 nM	US-10214512
methyl N-[14-[5-[2-fluoro-6-(trifluoromethoxy)phenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.22 nM	US-10214512
methyl N-[(14R)-14-[5-[5-fluoro-2-(trifluoromethoxy)phenyl]-1-oxidopyridin-1-ium-2-yl]-17-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.22 nM	US-10214512
methyl N-[(14R)-14-[5-[2-(difluoromethoxy)-6-fluorophenyl]-1-oxidopyridin-1-ium-2-yl]-10,10,17-trimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.22 nM	US-10214512
ethyl N-[14-[5-(3-chloro-2,6-difluorophenyl)-1-oxidopyridin-1-ium-2-yl]-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15-pentaen-5-yl]carbamate	KI	0.23 nM	US-10214512
2-{5-[5-chloro-2-(1H- tetrazol-1-yl)phenyl]-1- oxidopyridin-2-yl}-N- 1H-indazol-6-yl-3- phenylpropanamide	IC50	0.24 nM	US-9783530: Factor Xla inhibitors
methyl (9-(5-(3-chloro-2- fluoro-6-(1h-tetrazol-1- yl)phenyl)pyridin-2-yl)-4-oxo- 3-aza-1(1,3),2(1,2)- dibenzenacyclononaphane-24- yl)carbamate	KI	0.24 nM	US-10214512
methyl N-[(14S)-14-[5-[5-chloro-2-(1,3-oxazol-5-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.24 nM	US-10214512
(S)-2-(24-(((2-(tert-butoxy)ethoxy)carbonyl)amino)-4-oxo-3-aza -1(1,3),2(1,2)-dinenzenacyclononaphane-9-yl)-5-(3-chloro-2,6-difluorophenyl)pyridine 1-oxide	KI	0.24 nM	US-10214512
(S)-5-(3-chloro-2,6-difluorophenyl)-2-(24-(((2-hydroxyethoxy)carbonyl)amino)-4-oxo-3-aza-1(1,3),2(1,2) -dinenzenacyclononaphane-9-yl)pyridine 1-oxide	KI	0.24 nM	US-10214512
[14-[5-[5-chloro-2-(tetrazol-1-yl)phenyl]-1-oxidopyridin-1-ium-2-yl]-4-fluoro-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-yl]-pyrrolidin-1-ylmethanone	KI	0.24 nM	US-10214512
4-{[(2R)-2-{5-[5-chloro- 2-(1H-tetrazol-1- yl)phenyl]-1- oxidopyridin-2-yl}-3-(4- fluorophenyl)propanoyl] amino}benzoic acid	IC50	0.26 nM	US-9783530: Factor Xla inhibitors
5-(5-chloro-2-(4-(difluoromethyl)-1H-1,2,3-triazol-1-yl)phenyl)-2-(24-((methoxycarbonyl)amino)-4-oxo-3-aza-1(1,3),2(1,2)-dibenzenacy clononaphane-9-yl)pyridine 1-oxide	KI	0.26 nM	US-10214512

ChEMBL bioactivities

636 potent at pChembl≥5 of 765 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	Ki	0.16	nM	CHEMBL6039093
9.68	Ki	0.21	nM	CHEMBL5810881
9.62	Ki	0.24	nM	CHEMBL5795285
9.59	Ki	0.26	nM	CHEMBL5978240
9.54	Ki	0.29	nM	CHEMBL6034229
9.52	Ki	0.3	nM	CHEMBL5879132
9.48	Ki	0.33	nM	CHEMBL5981154
9.47	Ki	0.34	nM	CHEMBL5892465
9.44	Ki	0.36	nM	CHEMBL5928310
9.40	Ki	0.4	nM	CHEMBL5926090
9.37	Ki	0.43	nM	CHEMBL5759902
9.37	Ki	0.43	nM	CHEMBL5934781
9.36	Ki	0.44	nM	CHEMBL6041689
9.34	Ki	0.46	nM	CHEMBL5966546
9.31	Ki	0.49	nM	CHEMBL6021099
9.29	Ki	0.51	nM	CHEMBL5868013
9.28	Ki	0.53	nM	CHEMBL5780336
9.23	Ki	0.59	nM	CHEMBL5929651
9.22	Ki	0.6	nM	CHEMBL5807118
9.19	Ki	0.65	nM	CHEMBL6057268
9.18	Ki	0.66	nM	CHEMBL5749783
9.15	IC50	0.7	nM	CHEMBL5876651
9.15	Ki	0.7	nM	CHEMBL6061702
9.15	Ki	0.71	nM	CHEMBL6056231
9.14	Ki	0.73	nM	CHEMBL5888243
9.13	Ki	0.74	nM	CHEMBL5813304
9.11	Ki	0.77	nM	CHEMBL5952375
9.11	Ki	0.78	nM	CHEMBL5880383
9.11	Ki	0.78	nM	CHEMBL6059876
9.09	Ki	0.81	nM	CHEMBL6019883
9.09	Ki	0.81	nM	CHEMBL5842132
9.02	Ki	0.95	nM	CHEMBL5862641
8.99	Ki	1.02	nM	CHEMBL5859416
8.99	Ki	1.02	nM	CHEMBL5898771
8.97	Ki	1.08	nM	CHEMBL6047310
8.96	Ki	1.1	nM	CHEMBL6054755
8.92	IC50	1.2	nM	CHEMBL6044161
8.92	Ki	1.21	nM	CHEMBL5765808
8.89	Ki	1.29	nM	CHEMBL5836564
8.87	Ki	1.35	nM	CHEMBL5809425
8.87	Ki	1.35	nM	CHEMBL5950504
8.86	Ki	1.39	nM	CHEMBL6036933
8.85	Ki	1.43	nM	CHEMBL5940035
8.85	Ki	1.41	nM	CHEMBL5918900
8.82	Ki	1.5	nM	CHEMBL6032430
8.82	Ki	1.5	nM	CHEMBL5839959
8.81	Ki	1.55	nM	CHEMBL5995617
8.81	Ki	1.53	nM	CHEMBL5774338
8.80	Ki	1.57	nM	CHEMBL6063525
8.79	Ki	1.61	nM	CHEMBL5949503

PubChem BioAssay actives

141 with measured affinity, of 395 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
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	95174: Binding affinity against kallikrein	ki	<0.0001	uM
3-amino-N-[2-(3-chlorophenoxy)ethyl]-1-[[4-[(2-oxo-1-pyridinyl)methyl]phenyl]methyl]pyrazole-4-carboxamide	1930730: Inhibition of KLK1 (unknown origin)	ic50	0.0029	uM
(15S)-2-[(1-aminoisoquinolin-6-yl)amino]-15-methyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0040	uM
2-[(1-aminoisoquinolin-6-yl)amino]-15-methyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0060	uM
benzyl N-[(2R)-1-[(2S)-2-[[(1S)-4-methoxy-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate	95174: Binding affinity against kallikrein	ki	0.0061	uM
(4S)-4-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-6-aminohexanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-5-amino-5-oxopentanoic acid	702052: Inhibition of human KLK1 using Pro-Phe-Arg-MCA as substrate for 2 mins by spectrophotometric analysis	ki	0.0080	uM
(5R,11R)-11-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-16-cyclopropylsulfonyl-7-(2,2-difluoroethoxy)-5,13-dimethyl-2,13-diazatricyclo[13.3.1.16,10]icosa-1(19),6,8,10(20),15,17-hexaene-3,12-dione	1331373: Inhibition of tissue Kallikrein-1 (unknown origin)	ki	0.0094	uM
benzyl N-[(2S)-1-[(2S)-2-[[2,2-dimethyl-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate	95174: Binding affinity against kallikrein	ki	0.0095	uM
benzyl N-[(2S)-1-oxo-3,3-diphenyl-1-[(2S)-2-[[2-phenyl-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethyl]carbamoyl]pyrrolidin-1-yl]propan-2-yl]carbamate	95174: Binding affinity against kallikrein	ki	0.0095	uM
(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-7-cyclopropyl-4,15,17-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1316614: Inhibition of human kallikrein1 at 37 degC by chromogenic substrate assay	ki	0.0150	uM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1235268: Inhibition of human tissue kallikrein 1 measured for 30 mins	ki	0.0180	uM
6-carbamimidoyl-4-(5-ethylsulfonylfuran-3-yl)-N-phenylnaphthalene-2-carboxamide	150768: Binding affinity towards P-kallikrein	ki	0.0190	uM
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-4,15,17-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6(21),7,9,16,19-hexaene-3,12-dione	1315774: Inhibition of human HK1 using H-D-Val-Leu-Arg-AFC as substrate assessed as release of AFC after 10 to 120 mins by spectrofluorimetric method	ki	0.0210	uM
methyl 8-[[7-amino-1-[2-(4-carbamoylphenyl)ethylamino]-1,2-dioxoheptan-3-yl]carbamoyl]-2-[(2,5-difluorophenyl)methyl]-1,3-dioxo-6-(2-phenylethyl)-5,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxylate	95196: Compound was evaluated for its inhibitory activity against Kallikrein	ki	0.0210	uM
2-[(1-aminoisoquinolin-6-yl)amino]-7-tert-butylsulfonyl-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6,8,10(21),16(20),17-hexaene-3,12-dione	1235268: Inhibition of human tissue kallikrein 1 measured for 30 mins	ki	0.0220	uM
(5S,11R)-11-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-16-cyclopropylsulfonyl-7-(2,2-difluoroethoxy)-5,13-dimethyl-2,13-diazatricyclo[13.3.1.16,10]icosa-1(19),6,8,10(20),15,17-hexaene-3,12-dione	1331373: Inhibition of tissue Kallikrein-1 (unknown origin)	ki	0.0230	uM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-15,15-dimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0250	uM
(15R)-2-[(1-aminoisoquinolin-6-yl)amino]-15-methyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0250	uM
(2S)-2-[(1-aminoisoquinolin-6-yl)amino]-15,15-dimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0310	uM
N-[7-amino-1-[2-(4-carbamoylphenyl)ethylamino]-1,2-dioxoheptan-3-yl]-7-[(3,4-dichlorophenyl)methyl]-13,13-dimethyl-6,8-dioxo-5,7,9-triazatetracyclo[10.1.1.02,10.05,9]tetradec-2-ene-4-carboxamide	95196: Compound was evaluated for its inhibitory activity against Kallikrein	ki	0.0310	uM
4-[[4-[(4-carbamimidoyl-2-iodophenoxy)methyl]phenyl]methoxy]-3-iodobenzenecarboximidamide	652665: Inhibition of human kallikrein 1	ki	0.0310	uM
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-4,15,17-trimethyl-7-(trifluoromethoxy)-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1315774: Inhibition of human HK1 using H-D-Val-Leu-Arg-AFC as substrate assessed as release of AFC after 10 to 120 mins by spectrofluorimetric method	ki	0.0340	uM
benzyl N-[(2S)-1-[(2S)-2-[[4-methoxy-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]carbamate	95174: Binding affinity against kallikrein	ki	0.0340	uM
2-[(1-aminoisoquinolin-6-yl)amino]-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0350	uM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-4,15,15-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.0360	uM
N-[4-(aminomethyl)phenyl]-6-carbamimidoyl-4-(pyrimidin-2-ylamino)naphthalene-2-carboxamide	150768: Binding affinity towards P-kallikrein	ki	0.0400	uM
6-[(E)-2-phenylethenyl]-8-(pyrimidin-2-ylamino)naphthalene-2-carboximidamide	238464: Binding affinity value against kallikrein	ki	0.0420	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminobenzoyl)amino]-3-phenylpropanoyl]amino]-3-[4-(aminomethyl)cyclohexyl]propanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[2-(2,4-dinitroanilino)ethyl]pentanediamide	702054: Inhibition of human KLK1	ki	0.0500	uM
6-(2-phenylcyclopropyl)-8-(pyrimidin-2-ylamino)naphthalene-2-carboximidamide	238464: Binding affinity value against kallikrein	ki	0.0540	uM
1-[3-(aminomethyl)phenyl]-N-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	238463: Binding affinity determined against human kallikrein	ki	0.0610	uM
6-carbamimidoyl-4-(5-ethylsulfanylfuran-3-yl)-N-phenylnaphthalene-2-carboxamide	150768: Binding affinity towards P-kallikrein	ki	0.0690	uM
6-carbamimidoyl-N-(3-cyclopentyloxyphenyl)-4-(5-ethylsulfonylfuran-3-yl)naphthalene-2-carboxamide	150768: Binding affinity towards P-kallikrein	ki	0.0700	uM
8-(furan-3-yl)-6-[(E)-2-phenylethenyl]naphthalene-2-carboximidamide	238464: Binding affinity value against kallikrein	ki	0.0830	uM
2-[[(E)-3-[4-(4-carbamimidoylphenoxy)carbonylphenyl]-2-methylprop-2-enoyl]-prop-2-enylamino]acetic acid;methanesulfonic acid	95186: Concentration required to inhibit enzymatic cleavage of the chromogenic substrate (H-D-Pro-Phe-Arg-pNA) for plasma kallikrein in vitro.	ic50	0.0965	uM
6-carbamimidoyl-N-phenyl-4-(pyrimidin-2-ylamino)naphthalene-2-carboxamide	150768: Binding affinity towards P-kallikrein	ki	0.1000	uM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-propan-2-ylsulfonyl-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6,8,10(21),16(20),17-hexaene-3,12-dione	1235268: Inhibition of human tissue kallikrein 1 measured for 30 mins	ki	0.1000	uM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-ethylsulfonyl-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6,8,10(21),16(20),17-hexaene-3,12-dione	1235268: Inhibition of human tissue kallikrein 1 measured for 30 mins	ki	0.1000	uM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-ethylsulfonyl-17-methyl-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1235268: Inhibition of human tissue kallikrein 1 measured for 30 mins	ki	0.1000	uM
(2R,15R)-2-[(1-amino-8-fluoroisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-4,15,17-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1315774: Inhibition of human HK1 using H-D-Val-Leu-Arg-AFC as substrate assessed as release of AFC after 10 to 120 mins by spectrofluorimetric method	ki	0.1000	uM
methyl N-[3-[(2S)-1-[(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-2-(3,4-dimethoxyphenyl)acetyl]pyrrolidin-2-yl]-4-propan-2-ylsulfonylphenyl]carbamate	1325944: Inhibition of human tissue kallikrein using H-D-Val-Leu-Arg-AFC as substrate	ki	0.1100	uM
(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminocyclohexyl)-2-[(2-phenylacetyl)amino]propanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanamide	702054: Inhibition of human KLK1	ki	0.1100	uM
benzyl N-[(2S)-1-oxo-3-phenyl-1-[(2S)-2-[1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexylcarbamoyl]pyrrolidin-1-yl]propan-2-yl]carbamate	95174: Binding affinity against kallikrein	ki	0.1200	uM
N-(4-carbamimidoylphenyl)-3-ethoxy-2-hydroxybenzamide;hydrochloride	1624358: Inhibition of recombinant human N-terminal his-tagged KLK1 (19 to 262 residues) expressed in baculovirus infected sf9 insect cells using R110 labelled GSK3162232A as substrate measured every 30 secs intervals for 5 mins by Rhodamine110 dye-based fluorescence assay	ic50	0.1259	uM
(11R)-11-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-16-cyclopropylsulfonyl-7-(2,2-difluoroethoxy)-13-methyl-2,13-diazatricyclo[13.3.1.16,10]icosa-1(19),6,8,10(20),15,17-hexaene-3,12-dione	1331373: Inhibition of tissue Kallikrein-1 (unknown origin)	ki	0.1400	uM
(2S)-2-[(1-aminoisoquinolin-6-yl)amino]-4,15,15-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6(21),7,9,16(20),17-hexaene-3,12-dione	1301929: Inhibition of purified human tissue kallikrein 1 using H-D-Val-Leu-Arg-AFC as substrate	ki	0.1540	uM
6-(2-phenylethyl)-8-(pyrimidin-2-ylamino)naphthalene-2-carboximidamide	238464: Binding affinity value against kallikrein	ki	0.1560	uM
benzyl N-[(2S)-1-oxo-3,3-diphenyl-1-[(2S)-2-[1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexylcarbamoyl]pyrrolidin-1-yl]propan-2-yl]carbamate	95174: Binding affinity against kallikrein	ki	0.1600	uM
(4-carbamimidoylphenyl) 4-[(E)-3-[(2-ethoxy-2-oxoethyl)-prop-2-enylamino]-2-methyl-3-oxoprop-1-enyl]benzoate;methanesulfonic acid	95186: Concentration required to inhibit enzymatic cleavage of the chromogenic substrate (H-D-Pro-Phe-Arg-pNA) for plasma kallikrein in vitro.	ic50	0.1900	uM
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-4,15,17-trimethyl-7-(2-methylpyrazol-3-yl)-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1315774: Inhibition of human HK1 using H-D-Val-Leu-Arg-AFC as substrate assessed as release of AFC after 10 to 120 mins by spectrofluorimetric method	ki	0.2000	uM
(3R,8R,11S,14S,17S,20S,23S,26S,29S,32S)-3-amino-11,23-dibenzyl-20-[(1-carbamimidoylpiperidin-4-yl)methyl]-26-[3-(diaminomethylideneamino)propyl]-17,29-dimethyl-14-(2-methylpropyl)-2,10,13,16,19,22,25,28,31-nonaoxo-5,6-dithia-1,9,12,15,18,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-8-carboxylic acid	1262338: Inhibition of human KLK1 after 15 mins using Val-Leu-Lys-p-nitroanilide as substrate	ki	0.2010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-nitroaniline	affects binding, decreases activity, affects metabolic processing	2
Potassium	decreases activity, increases expression	2
propionaldehyde	increases expression	1
4-aminobenzamidine	affects binding, decreases activity	1
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	affects cotreatment, affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
ferrous sulfate	decreases activity	1
aniline	affects binding, decreases activity	1
ferric citrate	decreases activity	1
benzamidine	affects binding, decreases activity	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
pentanal	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Aluminum	decreases activity, affects binding	1
Benzo(a)pyrene	affects methylation	1
Calcium	decreases activity	1
Cisplatin	affects response to substance	1
Dobutamine	affects response to substance	1
Ethyl Methanesulfonate	increases expression	1
Hydrocortisone	increases export	1
Magnesium	decreases activity	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Sodium	decreases activity	1
Sodium, Dietary	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

ChEMBL screening assays

111 unique, capped per target: 108 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1930263	Binding	Inhibition of tissue kallikrein	The arginine mimicking β-amino acid β³hPhe(3-H₂N-CH₂) as S1 ligand in cyclotheonamide-based β-tryptase inhibitors. — Bioorg Med Chem
CHEMBL3865419	ADMET	Inhibition of human tissue kallikrein using H-D-Val-Leu-Arg-AFC as substrate	Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT03236818	PHASE4	UNKNOWN	Goal Oriented Strategy to Preserve Ejection Fraction Trial
NCT03344159	PHASE4	COMPLETED	Spironolactone Therapy in Chronic Stable Right HF Trial