HGFAC

Summary

HGFAC (HGF activator, HGNC:4894) is a protein-coding gene on chromosome 4p16.3, encoding Hepatocyte growth factor activator serine protease (Q04756). Serine protease that hydrolyzes the inactive zymogen hepatocyte growth factor (HGFsc) to an activated disulfide-linked heterodimer, then initiating hepatocyte growth factor receptor signaling pathway.

This gene encodes a member of the peptidase S1 protein family. The encoded protein is first synthesized as an inactive single-chain precursor before being activated to a heterodimeric form by endoproteolytic processing. It acts as serine protease that converts hepatocyte growth factor to the active form. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3083 — RefSeq curated summary.

At a glance

• GWAS associations: 55
• Clinical variants (ClinVar): 188 total — 2 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4894
Approved symbol	HGFAC
Name	HGF activator
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	HGFAP, HGFA
Ensembl gene	ENSG00000109758
Ensembl biotype	protein_coding
OMIM	604552
Entrez	3083

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 25 protein_coding, 2 retained_intron

ENST00000382774, ENST00000506132, ENST00000509689, ENST00000511533, ENST00000882381, ENST00000882382, ENST00000882383, ENST00000882384, ENST00000882385, ENST00000882386, ENST00000882387, ENST00000882388, ENST00000882389, ENST00000882390, ENST00000882391, ENST00000882392, ENST00000882393, ENST00000882394, ENST00000882395, ENST00000882396, ENST00000882397, ENST00000882398, ENST00000882399, ENST00000882400, ENST00000882401, ENST00000882402, ENST00000943280

RefSeq mRNA: 2 — MANE Select: NM_001528 NM_001297439, NM_001528

CCDS: CCDS3369, CCDS75098

Canonical transcript exons

ENST00000382774 — 14 exons

Exon	Start	End
ENSE00000699356	3442732	3442912
ENSE00000699357	3443050	3443146
ENSE00000699358	3443341	3443420
ENSE00000699359	3444039	3444161
ENSE00000699360	3444311	3444442
ENSE00000699364	3445265	3445350
ENSE00001493333	3449237	3449486
ENSE00001493344	3441968	3442118
ENSE00003465945	3444819	3444993
ENSE00003577733	3448128	3448276
ENSE00003635347	3446042	3446294
ENSE00003670730	3447895	3448035
ENSE00003682435	3447492	3447631
ENSE00003690432	3444623	3444733

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 99.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8131 / max 304.1891, expressed in 19 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46712	0.7833	17
46713	0.0298	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.00	gold quality
liver	UBERON:0002107	95.11	gold quality
right testis	UBERON:0004534	80.96	gold quality
left testis	UBERON:0004533	79.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.43	gold quality
cortical plate	UBERON:0005343	77.05	gold quality
right uterine tube	UBERON:0001302	76.90	gold quality
ganglionic eminence	UBERON:0004023	76.72	gold quality
testis	UBERON:0000473	76.43	gold quality
cerebellar hemisphere	UBERON:0002245	76.12	gold quality
cerebellar cortex	UBERON:0002129	75.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.36	gold quality
cerebellum	UBERON:0002037	72.96	gold quality
right frontal lobe	UBERON:0002810	72.43	gold quality
ventricular zone	UBERON:0003053	70.72	gold quality
adenohypophysis	UBERON:0002196	70.21	gold quality
cingulate cortex	UBERON:0003027	69.82	gold quality
anterior cingulate cortex	UBERON:0009835	69.52	gold quality
pituitary gland	UBERON:0000007	69.14	gold quality
amygdala	UBERON:0001876	67.76	gold quality
mucosa of stomach	UBERON:0001199	67.46	gold quality
caudate nucleus	UBERON:0001873	66.05	gold quality
embryo	UBERON:0000922	65.69	gold quality
nucleus accumbens	UBERON:0001882	65.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.25	gold quality
type B pancreatic cell	CL:0000169	65.10	gold quality
putamen	UBERON:0001874	64.89	gold quality
tendon of biceps brachii	UBERON:0008188	64.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	63.57	gold quality
metanephros cortex	UBERON:0010533	63.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, HNF1A

Literature-anchored findings (GeneRIF, showing 12)

• HAI-1 (serine peptidase inhibitor, Kunitz type 1) specifically traps active form of HGF activator on cellular surface and regulates HGF activation in pericellular microenvironment. (PMID:11013244)
• the HGF-activator has a role in multiple myeloma cells’ catalysis of hepatocyte growth factor (HGF) activation (PMID:15172968)
• HGF/MET signaling and aberrant HGF-activator expression is associated with diffuse large B-cell lymphoma (PMID:16189274)
• KLK4 and KLK5 activate pro-HGFA. (PMID:18221492)
• Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer. (PMID:18422749)
• the activated form of HGFA is present at high levels in serum and bone marrow of myeloma patients, thus providing a necessary prerequisite for the activation of HGF. (PMID:18691255)
• Results suggest that hepatocyte growth factor activator is a major serum activator of pro-macrophage-stimulating protein. (PMID:19456860)
• Based upon ethnicity-stratified single-variant association analysis and trans-ethnic meta-analysis of 6201 participants of the Multi-Ethnic Study of Atherosclerosis, discovered 5 common and low-frequency variants: HGF missense polymorphism rs5745687 (p.E299K) and 4 variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC.[Meta-analysis] (PMID:25998175)
• Hypermethylation around the promoter region contributed to the decreased expression of HGFAC. HGFAC may be a useful and predictive biomarker for the prognosis of liver cancer patients. (PMID:30635948)
• Role of hypoxia on microRNA-dependant regulation of HGFA - HGF - c-Met signalling pathway in human progenitor and mature endothelial cells. (PMID:36182093)
• HGFAC is a ChREBP-regulated hepatokine that enhances glucose and lipid homeostasis. (PMID:36413406)
• miR-4270 suppresses hepatocellular carcinoma progression by inhibiting DNMT3A-mediated methylation of HGFAC promoter. (PMID:38077422)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hgfac	ENSMUSG00000029102
rattus_norvegicus	Hgfac	ENSRNOG00000009572

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), F9 (ENSG00000101981), F10 (ENSG00000126218), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), PRSS55 (ENSG00000184647), CFD (ENSG00000197766), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Protein

Protein identifiers

Hepatocyte growth factor activator serine protease — Q04756 (reviewed: Q04756)

Alternative names: Serine protease HGFAC

All UniProt accessions (2): Q04756, D6RAR4

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that hydrolyzes the inactive zymogen hepatocyte growth factor (HGFsc) to an activated disulfide-linked heterodimer, then initiating hepatocyte growth factor receptor signaling pathway.

Subunit / interactions. Heterodimer of a short chain and a long chain linked by a disulfide bond.

Subcellular location. Secreted.

Tissue specificity. Liver.

Post-translational modifications. The active form of HGFAC presents in the serum is derived from the COOH-terminal region of the precursor by the cleavage of bonds between Arg-372 and Val-373 and Arg-407 and Ile-408.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (2): NP_001284368, NP_001519* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000083	Fibronectin_type1	Domain
IPR000562	FN_type2_dom	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR014394	Coagulation_fac_XII/HGFA	Family
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR036943	FN_type2_sf	Homologous_superfamily
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR050127	Serine_Proteases_S1	Family

Pfam: PF00008, PF00040, PF00051, PF00089

UniProt features (78 total): disulfide bond 21, strand 20, glycosylation site 6, domain 6, helix 6, sequence variant 5, turn 4, active site 3, site 2, chain 2, signal peptide 1, propeptide 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2R0L	X-RAY DIFFRACTION	2.2
3K2U	X-RAY DIFFRACTION	2.35
1YC0	X-RAY DIFFRACTION	2.6
1YBW	X-RAY DIFFRACTION	2.7
2WUC	X-RAY DIFFRACTION	2.7
2WUB	X-RAY DIFFRACTION	2.9
2R0K	X-RAY DIFFRACTION	3.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04756-F1	75.81	0.38

Antibody-complex structures (SAbDab): 5 — 2R0K, 2R0L, 2WUB, 2WUC, 3K2U

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 (5): 447 (charge relay system); 497 (charge relay system); 598 (charge relay system); 372–373 (cleavage); 407–408 (cleavage)

Disulfide bonds (21): 108–133, 122–148, 164–175, 169–186, 188–197, 202–230, 228–237, 245–256, 250–267, 269–278, 286–367, 307–349, 338–362, 394–521, 394, 432–448, 440–510, 521, 535–604, 567–583 …

Glycosylation sites (6): 40, 48, 290, 468, 492, 546

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6806942	MET Receptor Activation

MSigDB gene sets: 114 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GNF2_GSTM1, GNF2_HPN, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, HNF1_Q6, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, RGTTAMWNATT_HNF1_01, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, CAIRO_HEPATOBLASTOMA_DN, chr4p16, GNF2_HPX

GO Biological Process (3): proteolysis (GO:0006508), blood coagulation (GO:0007596), zymogen activation (GO:0031638)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), rough endoplasmic reticulum (GO:0005791), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by MET	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
protein processing	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
endoplasmic reticulum	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4145 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HGFAC	SPINT1	O43278	994
HGFAC	SPINT2	O43291	939
HGFAC	MET	P08581	719
HGFAC	GFAP	P14136	667
HGFAC	NES	P48681	581
HGFAC	RBFOX3	A6NFN3	541
HGFAC	OLIG2	Q13516	509
HGFAC	SLC1A3	P43003	508
HGFAC	FABP7	O15540	507
HGFAC	EMX1	Q04741	506
HGFAC	S100B	P04271	466
HGFAC	ALDH1L1	O75891	456
HGFAC	GJB6	O95452	419
HGFAC	SHH	Q15465	413
HGFAC	ASCL1	P50553	393

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SPINT1	HGFAC	psi-mi:“MI:0407”(direct interaction)	0.690
HGFAC		psi-mi:“MI:0407”(direct interaction)	0.560
HGFAC	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
HGFAC	CCHCR1	psi-mi:“MI:0915”(physical association)	0.560
HGFAC	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
HGFAC	GOLM1	psi-mi:“MI:0915”(physical association)	0.560
HGFAC	VSIG1	psi-mi:“MI:0915”(physical association)	0.560
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
APBB3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SERPINA5	ZZEF1	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
SPINT1	FOXK1	psi-mi:“MI:0914”(association)	0.530
HGFAC	SPINT1	psi-mi:“MI:0407”(direct interaction)	0.440
HGF	HGFAC	psi-mi:“MI:0194”(cleavage reaction)	0.440
RABGEF1	GAK	psi-mi:“MI:0914”(association)	0.350
APBB2	APBB1	psi-mi:“MI:0914”(association)	0.350
TMEM74	KLRG2	psi-mi:“MI:0914”(association)	0.350
HGFAC	POTEF	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
APBB2	LAMTOR5	psi-mi:“MI:0914”(association)	0.350
SPINT1	CPM	psi-mi:“MI:0914”(association)	0.350
SPINT2	SPAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): HGFAC (Affinity Capture-MS), HGFAC (Affinity Capture-MS), HGFAC (Affinity Capture-MS), HGFAC (Affinity Capture-MS), HGFAC (Affinity Capture-MS), HGFAC (Affinity Capture-MS), RAB11FIP5 (Co-fractionation), HGFAC (Two-hybrid), HGFAC (Two-hybrid), GOLM1 (Two-hybrid), SLC30A2 (Two-hybrid), CCHCR1 (Two-hybrid), RAE1 (Affinity Capture-MS), HGFAC (Affinity Capture-MS), HGFAC (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, D3ZTE0, G3V801, O08762, O43866, O75636, O95428, O97507, P00748, P22457, P56730, P58215, P69525, P69526, P85521, P98140, Q02853, Q04756, Q04962, Q24K22, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q499S5, Q4G0T1, Q5G265, Q5G268, Q5G269, Q5G270, Q5G271, Q5IJ48, Q6QNF4, Q70UZ7, Q769J6, Q76LX8, Q7Z410, Q80YA8, Q80YC5

Diamond homologs: A0A096LNW5, A2RUV0, B4DH59, B8JI71, G3I6Z6, O35516, O75882, P07207, P0DPK3, P0DPK4, P10040, P21783, P46530, P46531, P98160, Q01705, Q04721, Q04756, Q07008, Q20911, Q7Z3S9, Q99466, Q99J86, Q9QW30, Q9UM47, Q9WU60, A0A6I8TBG6, A0A6J1W8N1, A6MFK8, B1AC87, B1AC88, B1AC89, B1AC90, B5U2W0, G5AE35, O15393, O18783, O97366, O97399, O97507

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	166
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2583026	GRCh37/hg19 4p16.3-15.32(chr4:85622-16900108)x1	Pathogenic
3246663	NC_000004.11:g.(?2822345)(3495228_?)del	Pathogenic

SpliceAI

2786 predictions. Top by Δscore:

Variant	Effect	Δscore
4:3442730:A:AG	acceptor_gain	1.0000
4:3442731:G:GG	acceptor_gain	1.0000
4:3442731:GAACC:G	acceptor_gain	1.0000
4:3443141:G:GT	donor_gain	1.0000
4:3443141:G:T	donor_gain	1.0000
4:3444037:A:AG	acceptor_gain	1.0000
4:3444038:G:GG	acceptor_gain	1.0000
4:3444622:GCTT:G	acceptor_gain	1.0000
4:3444734:G:GA	donor_loss	1.0000
4:3444734:G:GG	donor_gain	1.0000
4:3445325:G:GT	donor_gain	1.0000
4:3446240:G:GT	donor_gain	1.0000
4:3447632:G:GG	donor_gain	1.0000
4:3447633:TGAGC:T	donor_loss	1.0000
4:3447634:GA:G	donor_loss	1.0000
4:3447893:A:AG	acceptor_gain	1.0000
4:3447894:G:GA	acceptor_gain	1.0000
4:3447894:GT:G	acceptor_gain	1.0000
4:3447894:GTC:G	acceptor_gain	1.0000
4:3447894:GTCCT:G	acceptor_gain	1.0000
4:3447994:G:GT	donor_gain	1.0000
4:3448032:GAGA:G	donor_gain	1.0000
4:3448034:GA:G	donor_gain	1.0000
4:3448036:G:GG	donor_gain	1.0000
4:3448124:ACAGA:A	acceptor_loss	1.0000
4:3448125:CAGAC:C	acceptor_loss	1.0000
4:3448126:A:AG	acceptor_gain	1.0000
4:3448126:AGAC:A	acceptor_gain	1.0000
4:3448127:G:GA	acceptor_gain	1.0000
4:3448127:GAC:G	acceptor_gain	1.0000

AlphaMissense

4229 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:3444907:G:C	W310C	1.000
4:3444907:G:T	W310C	1.000
4:3443341:G:C	W132C	0.999
4:3443341:G:T	W132C	0.999
4:3445292:G:C	W348C	0.999
4:3445292:G:T	W348C	0.999
4:3445325:G:C	W359C	0.999
4:3445325:G:T	W359C	0.999
4:3448019:G:C	W540C	0.999
4:3448019:G:T	W540C	0.999
4:3444905:T:A	W310R	0.998
4:3444905:T:C	W310R	0.998
4:3444989:T:A	C338S	0.998
4:3444990:G:C	C338S	0.998
4:3446283:C:G	C448W	0.998
4:3448017:T:A	W540R	0.998
4:3448017:T:C	W540R	0.998
4:3448190:T:A	C567S	0.998
4:3448191:G:C	C567S	0.998
4:3448238:T:A	C583S	0.998
4:3448238:T:C	C583R	0.998
4:3448239:G:C	C583S	0.998
4:3448271:T:A	C594S	0.998
4:3448272:G:C	C594S	0.998
4:3443342:T:A	C133S	0.997
4:3443343:G:C	C133S	0.997
4:3444991:C:G	C338W	0.997
4:3445288:C:A	P347H	0.997
4:3445290:T:A	W348R	0.997
4:3445290:T:C	W348R	0.997

dbSNP variants (sampled 300 via entrez): RS1000049963 (4:3440260 G>A,C), RS1000200470 (4:3444501 C>G,T), RS1000343588 (4:3447932 C>A,T), RS1000433435 (4:3446367 C>T), RS1000485574 (4:3443879 C>G), RS1000544867 (4:3443649 G>A,C), RS1000648609 (4:3447368 G>A), RS1000679698 (4:3447172 C>A,T), RS1000922488 (4:3446548 A>C,G), RS1001239822 (4:3449851 G>A), RS1001813705 (4:3439138 C>G,T), RS1002167665 (4:3442713 C>A,T), RS1002218709 (4:3449902 G>A), RS1002488439 (4:3441929 C>G,T), RS1002496737 (4:3441677 G>A)

Disease associations

OMIM: gene MIM:604552 | disease phenotypes: MIM:254300, MIM:609456, MIM:208150

GenCC curated gene-disease

Mondo (2): congenital myasthenic syndrome 10 (MONDO:0009690), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (2): Congenital myasthenic syndrome (Orphanet:590), Fetal akinesia deformation sequence (Orphanet:994)

HPO phenotypes

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

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST002147_9	Fibrinogen	2.000000e-08
GCST003043_98	Inflammatory bowel disease	1.000000e-07
GCST003044_21	Crohn’s disease	9.000000e-07
GCST003194_6	Fibrinogen levels	2.000000e-12
GCST004121_26	Fibrinogen levels	3.000000e-11
GCST004449_11	Hepatocyte growth factor levels	2.000000e-10
GCST004603_265	Platelet count	3.000000e-11
GCST004607_270	Plateletcrit	3.000000e-09
GCST005194_210	Coronary artery disease	2.000000e-06
GCST005196_114	Coronary artery disease	4.000000e-08
GCST005908_34	Height	5.000000e-15
GCST005989_8	Serum total protein levels	3.000000e-16
GCST006003_9	Triglyceride levels	1.000000e-14
GCST006019_27	Gamma glutamyl transferase levels	2.000000e-10
GCST006585_470	Blood protein levels	0.000000e+00
GCST006585_500	Blood protein levels	0.000000e+00
GCST006613_22	Triglycerides	1.000000e-16
GCST007096_108	Pulse pressure	1.000000e-09
GCST007269_93	Pulse pressure	4.000000e-16
GCST007876_15	Estimated glomerular filtration rate	4.000000e-11
GCST008058_29	Estimated glomerular filtration rate	5.000000e-11
GCST008074_108	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-17
GCST008074_2	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-15
GCST008074_39	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-29
GCST008076_1	Triglyceride levels	3.000000e-10
GCST008076_30	Triglyceride levels	2.000000e-14
GCST008076_66	Triglyceride levels	5.000000e-08
GCST008078_123	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-09
GCST008078_39	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-08
GCST008079_124	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004530	triglyceride measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0005763	pulse pressure measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0006334	total iron binding capacity
EFO:0004980	appendicular lean mass
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563716	Muscular Dystrophy, Congenital, Merosin-Positive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3351190 (SINGLE PROTEIN), CHEMBL3885586 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,796 (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
CHEMBL590799	CAMOSTAT	3	6,733

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

ChEMBL bioactivities

96 potent at pChembl≥5 of 117 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.43	Ki	3.7	nM	CHEMBL4464524
8.34	IC50	4.6	nM	CHEMBL5560415
8.14	Ki	7.2	nM	CHEMBL4587327
7.92	Ki	12	nM	CHEMBL3356596
7.92	IC50	12	nM	CHEMBL5564865
7.77	Ki	17	nM	CHEMBL3356606
7.68	Ki	21	nM	CHEMBL3356597
7.62	Ki	24	nM	CHEMBL3356603
7.60	Ki	25	nM	NAFAMOSTAT
7.58	IC50	26	nM	CHEMBL5074750
7.58	IC50	26	nM	CHEMBL5558547
7.52	Ki	30	nM	CHEMBL4454016
7.48	Ki	33	nM	CHEMBL4540950
7.48	IC50	33	nM	CHEMBL5559738
7.40	IC50	40	nM	CHEMBL5560759
7.28	Ki	53	nM	CHEMBL3356589
7.25	Ki	56	nM	CHEMBL3356600
7.24	Ki	57	nM	CHEMBL3356601
7.24	Ki	58	nM	CHEMBL3356592
7.22	Ki	60	nM	CHEMBL3356594
7.22	IC50	60	nM	CHEMBL4454016
7.21	IC50	61	nM	CHEMBL5568169
7.20	Ki	63	nM	CHEMBL3356605
7.19	Ki	65	nM	CHEMBL3356591
7.18	IC50	66	nM	CHEMBL4540950
7.10	Ki	79	nM	CHEMBL3356602
7.10	Ki	80	nM	CHEMBL3356593
7.09	Ki	81	nM	CHEMBL3356598
7.07	IC50	85	nM	CHEMBL5557087
7.02	Ki	96	nM	CHEMBL3356590
6.99	Ki	103	nM	CHEMBL3356604
6.82	IC50	150	nM	NAFAMOSTAT
6.80	Ki	160	nM	CHEMBL3780434
6.75	EC50	180	nM	CHEMBL3356607
6.74	Ki	182	nM	CHEMBL3356595
6.73	Ki	188	nM	LEUPEPTIN
6.64	Ki	230	nM	CHEMBL3781354
6.60	IC50	250	nM	CHEMBL5557551
6.52	IC50	300	nM	CHEMBL3403524
6.48	Ki	332	nM	CHEMBL3356599
6.46	Ki	350	nM	CHEMBL3780273
6.42	Ki	380	nM	CHEMBL3780548
6.37	Ki	430	nM	CHEMBL3780036
6.36	Ki	440	nM	CHEMBL3781673
6.33	Ki	468	nM	CHEMBL4561858
6.32	Ki	480	nM	CHEMBL3781349
6.31	EC50	490	nM	NAFAMOSTAT
6.28	Ki	520	nM	CHEMBL3780005
6.23	Ki	590	nM	CHEMBL3403520
6.22	IC50	600	nM	CHEMBL3403525

PubChem BioAssay actives

95 with measured affinity, of 167 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
4-[[[2-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-1,3-benzothiazole-6-carbonyl]amino]methyl]benzoic acid	1550523: Inhibition of recombinant HGFA serine protease domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition by fluorescence assay	ki	0.0037	uM
(4Z,7S,10R,13S)-13-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-10-(1H-indol-3-ylmethyl)-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),4,15,18-tetraene-7-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0046	uM
2-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamidobutanoyl]amino]-5-aminopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-N-piperidin-4-yl-1,3-benzothiazole-6-carboxamide	1550523: Inhibition of recombinant HGFA serine protease domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition by fluorescence assay	ki	0.0072	uM
(2S)-2-acetamido-6-amino-N-[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0120	uM
(7S,10S,13S)-13-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-10-benzyl-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),15,18-triene-7-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0120	uM
(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0170	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-4-methylpentanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0210	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-4-methylpentanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0240	uM
(6-carbamimidoylnaphthalen-2-yl) 4-(diaminomethylideneamino)benzoate	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0250	uM
2-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-aminohexanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]-1,3-benzothiazole-6-carboxamide	1810166: Inhibition of recombinant human HGFA serine protease domain using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay	ic50	0.0260	uM
(4E,7S,10S,13S)-13-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-10-(2-methylpropyl)-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),4,15,18-tetraene-7-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0260	uM
(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1575066: Inhibition of HGFA catalytic domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition and measured for 1 hr by fluorescence assay	ki	0.0300	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1575066: Inhibition of HGFA catalytic domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition and measured for 1 hr by fluorescence assay	ki	0.0330	uM
(7S,10R,13S)-13-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-10-(1H-indol-3-ylmethyl)-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),15,18-triene-7-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0330	uM
(7S,10S,13S)-13-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-10-(2-methylpropyl)-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),15,18-triene-7-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0400	uM
(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0530	uM
(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0560	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0570	uM
(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0580	uM
(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0600	uM
(9S,12S,15S)-15-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-12-(2-methylpropyl)-11,14-dioxo-2-oxa-10,13-diazatricyclo[15.2.2.13,7]docosa-1(19),3,5,7(22),17,20-hexaene-9-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0610	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-4-methylpentanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0630	uM
(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0650	uM
(2S)-2-acetamido-N-[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]butanediamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0790	uM
(2S)-2-acetamido-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0800	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0810	uM
(7S,10S,13S)-13-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-10-(1H-indol-3-ylmethyl)-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),15,18-triene-7-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.0850	uM
(2S)-2-acetamido-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.0960	uM
(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.1030	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-5-(methoxymethyl)-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.1600	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1171348: Inhibition of HGFA in human MDA-MB-231 cells assessed as inhibition of c-MET phosphorylation after 15 mins by immunoblotting	ec50	0.1800	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.1820	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.1880	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-5-(hydroxymethyl)-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.2300	uM
(8S,11S,14S)-14-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-11-(2-methylpropyl)-10,13-dioxo-2-oxa-9,12-diazatricyclo[14.2.2.23,6]docosa-1(18),3(22),4,6(21),16,19-hexaene-8-carboxamide	2081780: Inhibition of C-terminal 10-His tagged human recombinant HGFA (Gln36 to Ser655 residues) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis	ic50	0.2500	uM
(2-chloro-4-nitrophenyl) 4-(diaminomethylideneamino)benzoate	1195360: Inhibition of recombinant N-terminal His-tagged HGFA (unknown origin) expressed in baculovirus-infected Sf9 cells incubated for 30 mins prior to cromogenic substrate addition by spectrophotometry	ic50	0.3000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-N-[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-4-methylpentanamide	1171339: Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	ki	0.3320	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-5-(methanesulfonamido)-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.3500	uM
N-[1-[(1-benzylpiperidin-4-yl)methyl]-3-(3-carbamimidoylphenyl)-2-oxo-1,3-diazinan-5-yl]-2-phenylacetamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.3800	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-2-oxo-5-(phenylmethoxymethyl)-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.4300	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-5-(benzylsulfonylamino)-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.4400	uM
9H-fluoren-9-ylmethyl N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	1575066: Inhibition of HGFA catalytic domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition and measured for 1 hr by fluorescence assay	ki	0.4680	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-5-methyl-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.4800	uM
3-[5-(benzenesulfonamido)-3-[(1-benzylpiperidin-4-yl)methyl]-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.5200	uM
(2R)-2-(4-carbamimidoylanilino)-2-(7-ethyl-3-methyl-1-benzofuran-5-yl)-N-(1-methylimidazol-4-yl)sulfonylacetamide	1195365: Inhibition of HGFA (unknown origin) after 40 mins by Eadie-Hofstee plot analysis	ki	0.5900	uM
methyl 6-[4-(diaminomethylideneamino)benzoyl]oxynaphthalene-2-carboxylate	1195360: Inhibition of recombinant N-terminal His-tagged HGFA (unknown origin) expressed in baculovirus-infected Sf9 cells incubated for 30 mins prior to cromogenic substrate addition by spectrophotometry	ic50	0.6000	uM
(4-phenylpiperidin-4-yl) N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate;2,2,2-trifluoroacetic acid	1576186: Inhibition of recombinant HGFA serine protease domain (unknown origin) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay	ic50	0.7800	uM
(4-nitrophenyl) 4-(diaminomethylideneamino)benzoate	1195360: Inhibition of recombinant N-terminal His-tagged HGFA (unknown origin) expressed in baculovirus-infected Sf9 cells incubated for 30 mins prior to cromogenic substrate addition by spectrophotometry	ic50	0.8200	uM
3-[3-[(1-benzylpiperidin-4-yl)methyl]-5-hydroxy-2-oxo-1,3-diazinan-1-yl]benzenecarboximidamide	1288298: Inhibition of human recombinant hepatocyte growth factor activator using H2N(EEdansyl)GKQLRVVNGG (KDabcyl)-NH2 as substrate by fluorometric analysis	ki	0.8800	uM
9H-fluoren-9-ylmethyl N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	1575066: Inhibition of HGFA catalytic domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition and measured for 1 hr by fluorescence assay	ki	0.9630	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Hydrogen Peroxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3389934	Binding	Inhibition of recombinant HGFA (unknown origin) using Boc-QLR-AMC as substrate by chromogenic proteolytic assay	Inhibitors of HGFA, Matriptase, and Hepsin Serine Proteases: A Nonkinase Strategy to Block Cell Signaling in Cancer. — ACS Med Chem Lett

Clinical trials (associated diseases)

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