HPSE

Summary

HPSE (heparanase, HGNC:5164) is a protein-coding gene on chromosome 4q21.23, encoding Heparanase (Q9Y251). Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans.

Heparan sulfate proteoglycans are major components of the basement membrane and extracellular matrix. The protein encoded by this gene is an enzyme that cleaves heparan sulfate proteoglycans to permit cell movement through remodeling of the extracellular matrix. In addition, this cleavage can release bioactive molecules from the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10855 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 108 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001098540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5164
Approved symbol	HPSE
Name	heparanase
Location	4q21.23
Locus type	gene with protein product
Status	Approved
Aliases	HPA, HSE1, HPSE1
Ensembl gene	ENSG00000173083
Ensembl biotype	protein_coding
OMIM	604724
Entrez	10855

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000311412, ENST00000405413, ENST00000507150, ENST00000508891, ENST00000509906, ENST00000512196, ENST00000513463, ENST00000680713, ENST00000681769, ENST00000909494

RefSeq mRNA: 4 — MANE Select: NM_001098540 NM_001098540, NM_001166498, NM_001199830, NM_006665

CCDS: CCDS3602, CCDS54774, CCDS56337

Canonical transcript exons

ENST00000311412 — 12 exons

Exon	Start	End
ENSE00001181095	83310722	83310890
ENSE00001181096	83313114	83313287
ENSE00001181100	83319344	83319469
ENSE00001181103	83322219	83322364
ENSE00001181107	83292461	83295503
ENSE00001181111	83334556	83334848
ENSE00003519172	83300960	83301106
ENSE00003547663	83306203	83306317
ENSE00003556494	83309402	83309495
ENSE00003659937	83302150	83302268
ENSE00003674613	83308845	83308951
ENSE00003674917	83310031	83310078

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 93.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1700 / max 307.7238, expressed in 1048 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52926	7.6429	935
52927	0.5271	321

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	93.02	gold quality
mononuclear cell	CL:0000842	92.57	gold quality
leukocyte	CL:0000738	92.25	gold quality
esophagus squamous epithelium	UBERON:0006920	91.61	gold quality
epithelium of esophagus	UBERON:0001976	90.26	gold quality
gingiva	UBERON:0001828	90.10	gold quality
gingival epithelium	UBERON:0001949	89.76	gold quality
blood	UBERON:0000178	86.58	gold quality
penis	UBERON:0000989	86.55	gold quality
squamous epithelium	UBERON:0006914	85.73	gold quality
oral cavity	UBERON:0000167	85.53	gold quality
lower esophagus mucosa	UBERON:0035834	83.96	gold quality
granulocyte	CL:0000094	83.30	gold quality
esophagus mucosa	UBERON:0002469	82.78	gold quality
tongue squamous epithelium	UBERON:0006919	81.22	silver quality
germinal epithelium of ovary	UBERON:0001304	80.47	gold quality
mouth mucosa	UBERON:0003729	79.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.10	gold quality
minor salivary gland	UBERON:0001830	78.44	gold quality
palpebral conjunctiva	UBERON:0001812	77.49	gold quality
rectum	UBERON:0001052	77.20	gold quality
upper leg skin	UBERON:0004262	76.39	gold quality
placenta	UBERON:0001987	76.37	gold quality
mucosa of transverse colon	UBERON:0004991	75.92	gold quality
mammalian vulva	UBERON:0000997	75.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.47	gold quality
vermiform appendix	UBERON:0001154	73.43	gold quality
left ovary	UBERON:0002119	72.90	gold quality
saliva-secreting gland	UBERON:0001044	72.83	gold quality
skin of abdomen	UBERON:0001416	72.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, ESR1, HR, MBD2, NFKB1, NFKB, PAX1, POU4F1, PPARG, RELA, RUNX2, SP1, TP53, VSX2

miRNA regulators (miRDB)

126 targeting HPSE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872

Literature-anchored findings (GeneRIF, showing 40)

• Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro. (PMID:11759110)
• Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts. (PMID:11973358)
• REVIEW: Heparinase: involvement in cancer metastasis, angiogenesis and normal development (PMID:12027584)
• Results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials. (PMID:12029075)
• It was concluded that heparanase might play an important role in the development of invasion and metastasis of the gastric cancer. (PMID:12065771)
• Cell surface expression and secretion markedly promote tumor angiogenesis and metastasis. (PMID:12097647)
• structural recognition plays critical roles in tumor metastasis; specificity of the purified recombinant human heparanase (PMID:12213822)
• Heparanase-1 expression is associated with the metastatic potential of breast cancer (PMID:12219030)
• Heparanase participates in the structure damage and remodeling of abdominal aorta at matrix level, which contributes to abdominal aortic aneurysm (AAA) formation. (PMID:12509917)
• reduced heparanase mRNA expression may result in abnormal cell growth and correlate with esophageal squamous cell carcinoma progression (PMID:12679316)
• Expression correlates with tumor invasiveness patterns in human oral squamous cell carcinoma xenografts in SCID mice. (PMID:12824922)
• Intracellular processing of the heparin proteoglycan polysaccharide chains is catalyzed by heparanase. (PMID:12837765)
• results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer (PMID:12904690)
• heterodimer formation is necessary and sufficient for heparanase enzymatic activity in mammalian cells (PMID:12927802)
• heparanase gene transcription is regulated in activated T cells by early growth response 1 (PMID:14522979)
• NF-kappaB is an essential factor in the regulatory mechanisms of heparanase gene transcription. (PMID:14558943)
• glycosylation affected the kinetics of endoplasmic reticulum-to-Golgi transport and of secretion of the enzyme (PMID:14573609)
• Heparanase activates signal transduction pathways and, depending on its expression levels, may modulate tumor progression in glioma cells. (PMID:14633698)
• Increased HPR1 expression is associated with thyroid tumor malignancy and may significantly contribute to thyroid tumor metastases (PMID:14676122)
• characterization of the hpa-tg mice emphasizes the involvement of heparanase and heparan sulfate in processes such as embryonic implantation, food consumption, tissue remodeling, and vascularization (PMID:14769819)
• Tobacco etch virus protease cleavage sites of heparanase are engineered to provide evidence that proteolytic processing at both junctions between residues 109 and 110 and 157 and 158 leads to activation of the 65 kDa heparanase precursor. (PMID:14967027)
• Heparanase gene expression may play some roles in the pathogenesis of endometriosis, and it may participate the regulation of menstrual cycle and may be an important target of the trentment for endometriosis. (PMID:14989983)
• heparanase is translocated into the cell nucleus where it may degrade the nuclear heparan sulfate and thereby affect nuclear functions that are thought to be regulated by heparan sulfate (PMID:15034597)
• Heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. (PMID:15040016)
• In sites relatively remote from inflammatory foci, within blood vessels and extravascular tissues, heparanase can act as a T cell cytokine that is involved in regulating cell activation and behavior. (PMID:15100255)
• Inflammatory cytokines and fatty acids regulate endothelial cell heparanase expression. (PMID:15109255)
• Heparanase mRNA may be important to the loss of glomerular negative charge in GBM and lead to proteinuria in steroid responsive nephrotic syndrome. (PMID:15144715)
• Heparan sulfate is not only a substrate for, but also a regulator of, heparanase. (PMID:15292202)
• Point mutation may be one of the causes for enhanced heparanase mRNA expression in hepatocellular carcinoma. (PMID:15334672)
• one of the roles CREB plays in the acquisition of melanoma cells metastatic phenotype is affecting HPSE-1 activity (PMID:15368349)
• Heparanase is a critical determinant of myeloma dissemination and growth in vivo. (PMID:15471949)
• dysregulated heparanase expression may play a significant role in the pathogenesis of steroid-sensitive nephrotic syndrome, possibly through an abnormality in post-translational control of latent heparanase activation (PMID:15610235)
• Expression of heparanase was significantly more frequent in tumors of higher TNM stage, higher Dukes stage, higher vascular infiltration, higher lymph vessel infiltration and poor survival. (PMID:15625607)
• HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma (PMID:15645118)
• Results suggest that proheparanase processing at site 2 is brought about by cathepsin L-like proteases. (PMID:15659389)
• NF-kappaB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. (PMID:15682491)
• Heparanase plays a role in ovarian tissue remodeling during folliculogenesis and corpus luteum formation and regression. (PMID:15728796)
• HPR1 was expressed at a significantly higher frequency in the invasive comedo and DCIS with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was inversely associated with HS deposition in the extracellular basement membrane. (PMID:15737842)
• identified three potential heparin binding domains and provided evidence that one of these is mapped at the N terminus of the 50-kDa active heparanase subunit (PMID:15760902)
• Loss of heparan sulfsate in the glomerular basement membrane in diabetic nephropathy is attributable to accelerated heparan sulfate degradation by increased HPR1 expression. (PMID:15983219)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hpse	ENSDARG00000063634
mus_musculus	Hpse	ENSMUSG00000035273
rattus_norvegicus	Hpse	ENSRNOG00000002188
drosophila_melanogaster	CG14309	FBGN0038611

Paralogs (1): HPSE2 (ENSG00000172987)

Protein

Protein identifiers

Heparanase — Q9Y251 (reviewed: Q9Y251)

Alternative names: Endo-glucoronidase, Heparanase-1

All UniProt accessions (4): Q9Y251, A0A7P0TBD9, D6RAQ1, D6RHG4

UniProt curated annotations — full annotation on UniProt →

Function. Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as a procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.

Subunit / interactions. Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity. Interacts with TF; the interaction, inhibited by heparin, enhances the generation of activated factor X and activates coagulation. Interacts with HRG; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts with SDC1; the interaction enhances the shedding of SDC1. Interacts with HPSE2.

Subcellular location. Lysosome membrane. Secreted. Nucleus.

Tissue specificity. Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues. Also expressed in hair follicles, specifically in both Henle’s and Huxley’s layers of inner the root sheath (IRS) at anagen phase.

Post-translational modifications. Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme. N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility.

Activity regulation. Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium.

Miscellaneous. Escapes proteolytic cleavage, devoid of HS degradation activity.

Similarity. Belongs to the glycosyl hydrolase 79 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y251-1	1	yes
Q9Y251-2	2, 55 kDa, splice 5
Q9Y251-3	3, ex9-10del
Q9Y251-4	4, ex10del

RefSeq proteins (4): NP_001092010, NP_001159970, NP_001186759, NP_006656 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005199	Glyco_hydro_79	Family
IPR017853	GH_hydrolase_sf	Homologous_superfamily

Pfam: PF03662

Enzyme classification (BRENDA):

• EC 3.2.1.166 — heparanase (BRENDA: 11 organisms, 104 substrates, 150 inhibitors, 8 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FONDAPARINUX	0.0036–0.0118	3
2’-N,6’-O-BIS-SULFATED HEPARIN SULFATE DISACCHAR	0.0103	1
METHYL 2-DEOXY-6-O-SULFO-2-(SULFOAMINO)-ALPHA-D-	0.046	1
SULFATED PG545	0.0124	1
SULFATED TRISACCHARIDE FROM PG545	0.197	1

UniProt features (117 total): mutagenesis site 32, strand 27, helix 23, binding site 8, glycosylation site 6, splice variant 4, sequence conflict 3, chain 2, disulfide bond 2, sequence variant 2, region of interest 2, active site 2, turn 2, signal peptide 1, propeptide 1

Structure

Experimental structures (PDB)

58 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7RG8	X-RAY DIFFRACTION	1.3
7PR7	X-RAY DIFFRACTION	1.52
5L9Z	X-RAY DIFFRACTION	1.57
5E97	X-RAY DIFFRACTION	1.63
5E98	X-RAY DIFFRACTION	1.63
9O25	X-RAY DIFFRACTION	1.65
7PR8	X-RAY DIFFRACTION	1.66
7PRT	X-RAY DIFFRACTION	1.7
8OHQ	X-RAY DIFFRACTION	1.7
9O2C	X-RAY DIFFRACTION	1.7
6ZDM	X-RAY DIFFRACTION	1.71
5E9C	X-RAY DIFFRACTION	1.73
9O2K	X-RAY DIFFRACTION	1.73
5E8M	X-RAY DIFFRACTION	1.75
9O2H	X-RAY DIFFRACTION	1.75
8E07	X-RAY DIFFRACTION	1.8
8OHR	X-RAY DIFFRACTION	1.8
9O1S	X-RAY DIFFRACTION	1.8
9O28	X-RAY DIFFRACTION	1.81
9O21	X-RAY DIFFRACTION	1.82
9O20	X-RAY DIFFRACTION	1.83
5E9B	X-RAY DIFFRACTION	1.88
5L9Y	X-RAY DIFFRACTION	1.88
5LA4	X-RAY DIFFRACTION	1.9
9O1R	X-RAY DIFFRACTION	1.9
9O1T	X-RAY DIFFRACTION	1.9
9O1U	X-RAY DIFFRACTION	1.9
9O1W	X-RAY DIFFRACTION	1.9
9O1X	X-RAY DIFFRACTION	1.9
9O2L	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y251-F1	95.02	0.93

Antibody-complex structures (SAbDab): 1 — 9S8W

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 (2): 225 (proton donor); 343 (nucleophile)

Ligand- & substrate-binding residues (8): 158–162; 270–280; 296; 303; 348–350; 389–391; 62–64; 97

Disulfide bonds (2): 127–179, 437–542

Glycosylation sites (6): 162, 178, 200, 217, 238, 459

Mutagenesis-validated functional residues (32):

Position	Phenotype
156	alteration of the correct processing of heparanase which results in the cleavage at an upstream site in the linker pepti
156	normal processing.
158	no association with gs-modified heparin; when associated with k-158.
161	two-fold increase in the level of secretion upon addition of gs-modified heparin. no association with gs-modified hepari
162	faster electrophoretic migration typical of a size reduction and important decrease of secretion. larger size reduction;
178	faster electrophoretic migration typical of a size reduction and important decrease of secretion. larger size reduction;
200	faster electrophoretic migration typical of a size reduction and partial decrease in secretion. larger size reduction; w
217	faster electrophoretic migration typical of a size reduction and partial decrease in secretion. larger size reduction; w
225	loss of heparanase activity. no effect on hpse-mediated cell adhesion.
238	faster electrophoretic migration typical of a size reduction. larger size reduction and important decrease of secretion;
343	loss of heparanase activity.
367	strong decrease in heparanase activity.
378	no reduction in heparanase activity.
396	no reduction in heparanase activity.
414	abolishes processing, secretion and enzyme activity.
417	no effect on processing nor secretion. no enzyme activity detected.
459	faster electrophoretic migration typical of a size reduction. larger size reduction and important decrease of secretion;
525	no effect on processing nor secretion. no enzyme activity detected.
527	no effect on processing nor secretion. no enzyme activity detected.
528	no effect on processing nor secretion. no enzyme activity detected.
529	no effect on processing nor secretion. no enzyme activity detected.
531	abolishes processing, secretion and enzyme activity.
533	abolishes processing, secretion and enzyme activity.
534	abolishes processing, secretion and enzyme activity.
535	no effect on processing, secretion nor enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2024096	HS-GAG degradation
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 338 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PROTEIN_ACTIVATION_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_COAGULATION, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, LI_PROSTATE_CANCER_EPIGENETIC, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT

GO Biological Process (17): proteoglycan metabolic process (GO:0006029), cell-matrix adhesion (GO:0007160), positive regulation of vascular endothelial growth factor production (GO:0010575), positive regulation of blood coagulation (GO:0030194), heparan sulfate proteoglycan catabolic process (GO:0030200), heparin proteoglycan metabolic process (GO:0030202), positive regulation of osteoblast proliferation (GO:0033690), response to antibiotic (GO:0046677), regulation of hair follicle development (GO:0051797), positive regulation of hair follicle development (GO:0051798), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), angiogenesis involved in wound healing (GO:0060055), establishment of endothelial barrier (GO:0061028), vascular wound healing (GO:0061042), protein transmembrane transport (GO:0071806), cell adhesion (GO:0007155), wound healing (GO:0042060)

GO Molecular Function (6): beta-glucuronidase activity (GO:0004566), heparanase activity (GO:0030305), syndecan binding (GO:0045545), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), lysosome (GO:0005764), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), specific granule lumen (GO:0035580), lysosomal lumen (GO:0043202), membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Heparan sulfate/heparin (HS-GAG) metabolism	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
hair follicle development	2
lysosome	2
glycoprotein metabolic process	1
cell-substrate adhesion	1
positive regulation of cytokine production	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
blood coagulation	1
regulation of blood coagulation	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
proteoglycan catabolic process	1
heparan sulfate proteoglycan metabolic process	1
proteoglycan metabolic process	1
positive regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
response to chemical	1
regulation of hair cycle	1
regulation of multicellular organismal development	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of hair follicle development	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
angiogenesis	1
wound healing	1
endothelial cell development	1
angiogenesis involved in wound healing	1
protein transport	1
transmembrane transport	1
cellular process	1
response to wounding	1
tissue regeneration	1
glucuronidase activity	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
proteoglycan binding	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPSE	HGS	O14964	992
HPSE	ANOS1	P23352	692
HPSE	NEDD4L	Q96PU5	614
HPSE	SDC1	P18827	594
HPSE	VPS36	Q86VN1	584
HPSE	STAM	Q92783	553
HPSE	STAM2	O75886	535
HPSE	SRC	P12931	532
HPSE	LACRT	Q9GZZ8	506
HPSE	TFDP3	Q5H9I0	491
HPSE	GUSB	P08236	475
HPSE	USP8	P40818	465
HPSE	VPS25	Q9BRG1	448
HPSE	NDST2	P52849	447
HPSE	EXT1	Q16394	447
HPSE	FUT2	Q10981	447

IntAct

51 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
HPSE	OS9	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZSCAN5A	KDM1A	psi-mi:“MI:0914”(association)	0.530
HPSE	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
HPSE	LOC401309	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
	EIF3F	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
TEFM	A2ML1	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350
NR2C2	UBB	psi-mi:“MI:0914”(association)	0.350
RC3H2	CYP19A1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), HPSE (Affinity Capture-MS), DNAJA4 (Affinity Capture-MS), OS9 (Affinity Capture-MS), HPSE (Affinity Capture-Western), BAG2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), CLIC1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A4D0V7, C5H5C4, F6Q1T7, O70309, O75354, P17405, P18084, P18424, P22413, P50747, P52850, P58242, P61642, P80747, Q04519, Q0VBD0, Q0VD19, Q13219, Q52KP5, Q58CQ9, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q812F8, Q8BJQ9, Q8C1F4, Q8C419, Q8N5D6, Q8N6G5, Q8R116

Diamond homologs: B2RY83, Q6YGZ1, Q71RP1, Q8WWQ2, Q90YK5, Q9MYY0, Q9Y251, Q8L608, Q9FF10, X4Y2L4, Q9FZP1, Q9LRC8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	HPSE	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Major pathway of rRNA processing in the nucleolus and cytosol	7	10.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	10
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1874 predictions. Top by Δscore:

Variant	Effect	Δscore
4:83295419:T:TA	donor_gain	1.0000
4:83300958:A:AC	donor_gain	1.0000
4:83300959:C:CC	donor_gain	1.0000
4:83301107:C:CC	acceptor_gain	1.0000
4:83302146:TT:T	donor_loss	1.0000
4:83302148:A:AC	donor_gain	1.0000
4:83302148:AC:A	donor_loss	1.0000
4:83302149:C:CA	donor_gain	1.0000
4:83302149:CT:C	donor_gain	1.0000
4:83302149:CTT:C	donor_gain	1.0000
4:83302149:CTTG:C	donor_gain	1.0000
4:83302149:CTTGT:C	donor_gain	1.0000
4:83302264:TAATC:T	acceptor_gain	1.0000
4:83302273:T:TC	acceptor_gain	1.0000
4:83302275:G:C	acceptor_gain	1.0000
4:83302275:G:GC	acceptor_gain	1.0000
4:83302278:G:C	acceptor_gain	1.0000
4:83302278:G:GC	acceptor_gain	1.0000
4:83302281:G:GC	acceptor_gain	1.0000
4:83302282:T:C	acceptor_gain	1.0000
4:83302282:T:TC	acceptor_gain	1.0000
4:83308843:A:AC	donor_gain	1.0000
4:83308844:C:CC	donor_gain	1.0000
4:83309396:TATTA:T	donor_loss	1.0000
4:83309397:ATTAC:A	donor_loss	1.0000
4:83309398:TTACC:T	donor_loss	1.0000
4:83309399:TACCT:T	donor_loss	1.0000
4:83309400:A:AT	donor_loss	1.0000
4:83309401:C:A	donor_loss	1.0000
4:83309493:TAG:T	acceptor_gain	1.0000

AlphaMissense

3497 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:83306264:C:G	R382T	0.996
4:83308901:G:C	S345R	0.996
4:83308901:G:T	S345R	0.996
4:83308903:T:G	S345R	0.996
4:83313129:A:G	W220R	0.996
4:83313129:A:T	W220R	0.996
4:83306263:C:A	R382S	0.995
4:83306263:C:G	R382S	0.995
4:83306264:C:A	R382M	0.995
4:83306316:A:G	W365R	0.995
4:83306316:A:T	W365R	0.995
4:83313192:A:G	W199R	0.995
4:83313192:A:T	W199R	0.995
4:83313190:C:A	W199C	0.994
4:83313190:C:G	W199C	0.994
4:83322314:C:A	R93M	0.994
4:83322314:C:G	R93T	0.994
4:83308908:T:A	E343V	0.993
4:83322313:C:A	R93S	0.993
4:83322313:C:G	R93S	0.993
4:83334610:G:A	S58F	0.992
4:83295492:A:G	L495P	0.991
4:83308859:A:C	F359L	0.991
4:83308859:A:T	F359L	0.991
4:83308861:A:G	F359L	0.991
4:83308869:G:A	S356F	0.991
4:83310038:A:G	W295R	0.991
4:83310038:A:T	W295R	0.991
4:83334611:A:G	S58P	0.991
4:83301064:G:C	N456K	0.990

dbSNP variants (sampled 300 via entrez): RS1000020561 (4:83328258 G>A), RS1000074379 (4:83327963 G>A), RS1000093623 (4:83314751 G>T), RS10001403 (4:83298925 A>C,G,T), RS1000150091 (4:83298063 A>G), RS1000175054 (4:83303599 G>A,C), RS1000248580 (4:83335066 T>C), RS1000290582 (4:83294940 A>T), RS1000363346 (4:83301058 A>G), RS10004076 (4:83299365 A>C,G,T), RS1000477521 (4:83326787 G>A), RS1000513054 (4:83327131 G>C), RS1000618549 (4:83308774 C>G), RS1000685735 (4:83334031 G>A), RS1000690355 (4:83295900 T>G)

Disease associations

OMIM: gene MIM:604724 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009442_6	Age-related cognitive decline (executive function) (slope of z-scores)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3921 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 102,410 (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
CHEMBL1747	TOBRAMYCIN	4	65,562
CHEMBL265502	SURAMIN	3	36,848
CHEMBL4630621	RONEPARSTAT	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 3.2.1.- Glycosidases

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

Ligand	Action	Affinity	Parameter
pixatimod	Inhibition	8.21	pKi

Binding affinities (BindingDB)

8 measured of 8 human assays (8 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5279386	KI	6 nM
CHEMBL5291042	IC50	12 nM
CHEMBL5267246	IC50	20 nM
CHEMBL5268939	IC50	20 nM
CHEMBL5268973	IC50	416 nM
CHEMBL5266136	IC50	416 nM
CHEMBL5275724	IC50	4820 nM
CHEMBL5286425	IC50	4820 nM

ChEMBL bioactivities

481 potent at pChembl≥5 of 536 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.43	Ki	3.7	nM	CHEMBL2059500
8.30	IC50	5	nM	RONEPARSTAT
8.26	Ki	5.5	nM	CHEMBL2059243
8.24	Ki	5.8	nM	CHEMBL2059241
8.22	Ki	6	nM	CHEMBL2059242
8.22	Ki	6	nM	CHEMBL5279386
8.21	Ki	6.1	nM	CHEMBL2059499
8.19	Ki	6.4	nM	CHEMBL2059245
8.10	Ki	7.9	nM	MUPARFOSTAT SODIUM
8.08	Ki	8.4	nM	CHEMBL2059498
8.07	Ki	8.5	nM	CHEMBL2059246
8.04	Ki	9.1	nM	CHEMBL2059503
8.04	Ki	9.1	nM	CHEMBL2059504
7.98	Ki	10.5	nM	CHEMBL2059247
7.95	Ki	11.3	nM	CHEMBL2059505
7.92	IC50	12	nM	CHEMBL5282692
7.92	IC50	12	nM	CHEMBL5291042
7.92	IC50	12	nM	CHEMBL5279386
7.80	Ki	16	nM	CHEMBL2374307
7.70	Ki	20	nM	CHEMBL2059502
7.70	IC50	19.8	nM	CHEMBL5271999
7.70	IC50	19.8	nM	CHEMBL5267246
7.70	IC50	19.8	nM	CHEMBL5268939
7.70	IC50	20	nM	CHEMBL5562364
7.68	IC50	21	nM	CHEMBL5559476
7.65	Ki	22.3	nM	CHEMBL2059244
7.58	IC50	26	nM	CHEMBL5561988
7.54	IC50	29	nM	CHEMBL5549928
7.52	Ki	30	nM	CHEMBL2059510
7.52	IC50	30	nM	CHEMBL5557429
7.43	IC50	37	nM	CHEMBL5556661
7.39	IC50	41	nM	CHEMBL5557768
7.36	IC50	44	nM	CHEMBL5559840
7.25	IC50	56	nM	CHEMBL5564261
7.24	IC50	57	nM	CHEMBL5597984
7.12	IC50	75	nM	CHEMBL200597
7.10	IC50	80	nM	CHEMBL4286441
7.10	IC50	80	nM	CHEMBL6191726
7.09	IC50	82	nM	CHEMBL5560024
7.07	IC50	85	nM	CHEMBL5559647
7.04	IC50	92	nM	CHEMBL5561039
7.00	IC50	100	nM	CHEMBL6191409
6.96	Ki	111	nM	CHEMBL2059508
6.92	IC50	120	nM	CHEMBL5432881
6.91	IC50	123	nM	CHEMBL2059499
6.89	IC50	130	nM	CHEMBL2349246
6.82	IC50	150	nM	CHEMBL199610
6.82	IC50	150	nM	CHEMBL200541
6.82	IC50	150	nM	CHEMBL372737
6.80	IC50	160	nM	CHEMBL4576477

PubChem BioAssay actives

452 with measured affinity, of 705 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
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0037	uM
hexadecasodium;[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2S,3S,4R,5R,6R)-2-[3-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]propoxy]-4,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0055	uM
tridecasodium;[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2S,3S,4R,5R,6R)-2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0058	uM
tridecasodium;[(2R,3S,4S,5R,6S)-2-[(2S,3R,4S,5S,6R)-6-[(2S,3R,4S,5S,6R)-6-[(2R,3R,4S,5S,6R)-6-[[(2R,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-2-yl]peroxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	1953680: Binding affinity to heparanase (unknown origin) assessed as inhibition constant	ki	0.0060	uM
tridecasodium;[(2R,3R,4R,5S,6S)-5-[(2R,3S,4S,5R,6R)-4-[(2R,3S,4S,5R,6R)-3,5-disulfonatooxy-6-(sulfonatooxymethyl)-4-[(2R,3S,4S,5R,6R)-3,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-6-[3-(octadecanoylamino)propoxy]-3,4-disulfonatooxyoxan-2-yl]methyl sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0060	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0061	uM
decasodium;[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2S,3S,4R,5R,6R)-2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0064	uM
decasodium;[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2S,3S,4S,5R,6R)-2-[3-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]propoxy]-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0084	uM
decasodium;[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2S,3S,4R,5R,6R)-2-[3-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]propoxy]-4,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0085	uM
tridecasodium;[(2R,3R,4S,5R,6R)-3-[(2R,3R,4S,5R,6R)-5-[(2R,3R,4S,5R,6R)-3,4-disulfonatooxy-6-(sulfonatooxymethyl)-5-[(2R,3R,4S,5R,6R)-3,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-6-[3-(octadecanoylamino)propoxy]-4,5-disulfonatooxyoxan-2-yl]methyl sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0091	uM
decasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0091	uM
decasodium;[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2S,3S,4S,5R,6R)-2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0105	uM
decasodium;[(2R,3R,4S,5R,6R)-3-[(2R,3R,4S,5R,6R)-3,4-disulfonatooxy-6-(sulfonatooxymethyl)-5-[(2R,3R,4S,5R,6R)-3,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-6-[3-(octadecanoylamino)propoxy]-4,5-disulfonatooxyoxan-2-yl]methyl sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0113	uM
tridecasodium;[(2S,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6S)-6-[(2R,3R,4S,5R,6S)-6-[(2R,3R,4S,5R,6R)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	1946682: Inhibition of recombinant human HPSE expressed in insect cells by fondaparinux assay	ic50	0.0120	uM
decasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0160	uM
decasodium;[(2R,3S,4S,5R,6S)-2-[(2S,3R,4S,5S,6R)-6-[(2R,3R,4S,5S,6R)-6-[[(2R,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-2-yl]peroxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	1953681: Inhibition of heparanase (unknown origin) incubated for 18 hrs by fondaparinux assay	ic50	0.0198	uM
decasodium;[(2S,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6S)-6-[(2R,3R,4S,5R,6R)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	1946682: Inhibition of recombinant human HPSE expressed in insect cells by fondaparinux assay	ic50	0.0198	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[[(3R,5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-5-oxo-5-(prop-2-ynylamino)pentan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0200	uM
tetradecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[[(4R)-4-[(3S,5S,8R,9S,10S,12S,13R,14S,17R)-12-acetyloxy-10,13-dimethyl-3-sulfonatooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0200	uM
tridecasodium;[(2R,3R,4S,5R,6R)-3-[(2R,3R,4S,5R,6R)-5-[(2R,3R,4S,5R,6R)-3,4-disulfonatooxy-6-(sulfonatooxymethyl)-5-[(2R,3R,4S,5R,6R)-3,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-6-[11-[11-[4-[[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]methyl]triazol-1-yl]undecanoylamino]undecoxy]-4,5-disulfonatooxyoxan-2-yl]methyl sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0210	uM
heptasodium;[(2R,3S,4S,5R,6R)-2-[(2S,3S,4R,5R,6R)-2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0223	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[11-(11-azidoundecanoylamino)undecoxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0260	uM
tridecasodium;[(2R,3R,4S,5R,6R)-3-[(2R,3R,4S,5R,6R)-5-[(2R,3R,4S,5R,6R)-3,4-disulfonatooxy-6-(sulfonatooxymethyl)-5-[(2R,3R,4S,5R,6R)-3,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-6-[6-[11-[4-[[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]methyl]triazol-1-yl]undecanoylamino]hexoxy]-4,5-disulfonatooxyoxan-2-yl]methyl sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0290	uM
nonadecasodium;[(2R,3R,4S,5R,6R)-3-[(2R,3R,4S,5R,6R)-5-[(2R,3R,4S,5R,6R)-5-[(2R,3R,4S,5R,6R)-5-[(2R,3R,4S,5R,6R)-3,4-disulfonatooxy-6-(sulfonatooxymethyl)-5-[(2R,3R,4S,6R)-3,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-3,4-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-3,4-disulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-6-[3-(octadecanoylamino)propoxy]-4,5-disulfonatooxyoxan-2-yl]methyl sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0300	uM
heptasodium;[(2S,3R,4S,5S,6R)-2-[(2R,3R,4S,5R,6R)-6-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.0300	uM
nonadecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0370	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[[(3S,5S,8S,9S,10S,14R,17R)-17-[(2R,6R)-7-azido-6-methylheptan-2-yl]-10-methyl-1,2,3,4,5,6,7,8,9,11,12,13,14,15,16,17-hexadecahydrocyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0410	uM
nonadecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6S)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0440	uM
tridecasodium;(2R,4R,5R,6S)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[3-(octadecanoylamino)propoxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxane-3-sulfonate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0560	uM
(5S,6R,7R,8S)-7,8-dihydroxy-2-[2-(3-phenoxyphenyl)ethyl]-6-(2-phenylethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid	2118850: Inhibition of HPSE1 (unknown origin)	ic50	0.0570	uM
1,3-bis[4-(5,6-dimethyl-1H-benzimidazol-2-yl)phenyl]urea	258340: Inhibitory activity against heparanase from human platelets	ic50	0.0750	uM
2-[[2-[2-[4-[[4-[5-[2-(carboxymethylamino)-2-oxoethyl]-1,3-benzoxazol-2-yl]-2-fluorophenyl]carbamothioylamino]-3-fluorophenyl]-1,3-benzoxazol-5-yl]acetyl]amino]acetic acid	1419026: Inhibition of recombinant HPSE (unknown origin) using fondaparinux as substrate incubated for 3 hrs in absence of light by WST1 assay	ic50	0.0800	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6S)-6-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0820	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[6-(11-azidoundecanoylamino)hexoxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0850	uM
tridecasodium;[(2R,3R,4S,5R,6R)-2-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-[3-[4-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]propoxy]-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	2086020: Inhibition of recombinant human heparanase expressed in Insect cells assessed as fondaparinux cleavage by measuring disaccharide product incubated for 18 to 21 hrs	ic50	0.0920	uM
tetrasodium;[(2S,3S,4S,5R,6R)-2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate	672592: Inhibition of human recombinant heparanase after 2 to 24 hrs by WST1 dye based fondaparinux assay	ki	0.1110	uM
2-[4-[[3-[[4-(5-carboxy-1,3-dioxoisoindol-2-yl)-2-chlorophenyl]carbamoyl]benzoyl]amino]-3-chlorophenyl]-1,3-dioxoisoindole-5-carboxylic acid	1974822: Inhibition of heparanase (unknown origin)	ic50	0.1200	uM
5-[3-(octadecanoylamino)-5-oxo-4H-pyrazol-1-yl]-2-phenoxybenzenesulfonic acid	738329: Inhibition of recombinant heparanase catalytic stie (unknown origin) expressed in Escherichia coli BL21 (DE3)	ic50	0.1300	uM
1,3-bis[4-(6-methyl-1H-benzimidazol-2-yl)phenyl]urea	258340: Inhibitory activity against heparanase from human platelets	ic50	0.1500	uM
1,3-bis[4-(4-methyl-1H-benzimidazol-2-yl)phenyl]urea	258340: Inhibitory activity against heparanase from human platelets	ic50	0.1500	uM
1-[4-(1H-benzimidazol-2-yl)phenyl]-3-[4-(4-methyl-1H-benzimidazol-2-yl)phenyl]urea	258340: Inhibitory activity against heparanase from human platelets	ic50	0.1500	uM
N-[4-[[4-(1H-benzimidazol-2-yl)-2-fluoroanilino]methyl]phenyl]-3-bromo-4-methoxybenzamide	1529610: Inhibition of recombinant HPSE GS3 (unknown origin) using fondaparinux as substrate incubated for 3 hrs in absence of light by WST1 based colorimetry	ic50	0.1600	uM
2-[2-[4-[[4-[5-(carboxymethyl)-1,3-benzoxazol-2-yl]-2-fluorophenyl]carbamoylamino]-3-fluorophenyl]-1,3-benzoxazol-5-yl]acetic acid	1419026: Inhibition of recombinant HPSE (unknown origin) using fondaparinux as substrate incubated for 3 hrs in absence of light by WST1 assay	ic50	0.1800	uM
2-[3-[5-(4-chlorophenyl)-1,3-benzoxazol-2-yl]-4-(propylamino)phenyl]-1,3-dioxoisoindole-5-carboxylic acid	383554: Inhibition of heparanase	ic50	0.1995	uM
2-[2-[4-[(E)-3-(3-bromoanilino)-3-oxoprop-1-enyl]-2-fluorophenyl]-1,3-benzoxazol-5-yl]acetic acid	383554: Inhibition of heparanase	ic50	0.1995	uM
2-[3-[5-(1,3-benzodioxol-5-yl)-1,3-benzoxazol-2-yl]-4-methoxyphenyl]-1,3-dioxoisoindole-5-carboxylic acid	383554: Inhibition of heparanase	ic50	0.1995	uM
2-[2-[4-[(E)-3-(2,4-dichloroanilino)-3-oxoprop-1-enyl]-2-fluorophenyl]-1,3-benzoxazol-5-yl]acetic acid	383554: Inhibition of heparanase	ic50	0.1995	uM
2-[2-[4-[(E)-3-(3,4-dichloroanilino)-3-oxoprop-1-enyl]-2-fluorophenyl]-1,3-benzoxazol-5-yl]acetic acid	383554: Inhibition of heparanase	ic50	0.1995	uM
2-[3-[5-(4-fluorophenyl)-1,3-benzoxazol-2-yl]-4-(propylamino)phenyl]-1,3-dioxoisoindole-5-carboxylic acid	1953689: Inhibition of human heparanase assessed as reduction in basic fibroblast growth factor binding incubated for 2 hrs by microplate reader assay	ic50	0.2000	uM
2-[2-[4-[[(E)-3-(4-bromophenyl)prop-2-enoyl]amino]-2-fluorophenyl]-1,3-benzoxazol-5-yl]acetic acid	1953689: Inhibition of human heparanase assessed as reduction in basic fibroblast growth factor binding incubated for 2 hrs by microplate reader assay	ic50	0.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
phosphomannopentaose sulfate	affects abundance, decreases activity, decreases reaction, increases activity	3
Nickel	decreases expression, increases expression	3
sulforaphane	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Acrolein	increases oxidation, increases abundance, affects cotreatment, decreases expression	2
Vehicle Emissions	affects expression, increases reaction, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Particulate Matter	affects expression, increases reaction, decreases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression, decreases reaction, increases activity	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
abrine	decreases expression	1

ChEMBL screening assays

72 unique, capped per target: 72 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1072345	Binding	Inhibition of human recombinant heparanase	Synthesis and biological evaluation of polysulfated oligosaccharide glycosides as inhibitors of angiogenesis and tumor growth. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TW	Abcam HeLa HPSE KO	Cancer cell line	Female
CVCL_B8HM	Abcam HCT 116 HPSE KO	Cancer cell line	Male
CVCL_B9JX	Abcam A-549 HPSE KO	Cancer cell line	Male
CVCL_D2FL	Abcam MCF-7 HPSE KO	Cancer cell line	Female
CVCL_SR65	HAP1 HPSE (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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