3.2.1.166: heparanase
This is an abbreviated version!
For detailed information about heparanase, go to the full flat file.
Word Map on EC 3.2.1.166
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3.2.1.166
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metastasis
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proteoglycans
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angiogenesis
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endothelial
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heparin
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endoglycosidase
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basement
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glycosaminoglycans
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melanoma
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vessel
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oligosaccharide
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platelet
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syndecan-1
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hspgs
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node
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angiogenic
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myeloma
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nephropathy
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anticoagulant
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glycocalyx
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clinicopathological
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metalloproteinases
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glomerular
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procoagulant
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heparin-binding
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antimetastatic
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heparinase
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neovascularization
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fgf-2
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extravasation
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bfgf
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perlecan
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subendothelial
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matrigel
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microvessel
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chondroitin
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pro-tumorigenic
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o-sulfation
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matrix-degrading
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vegf-c
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pharmacology
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glypicans
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diagnostics
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proangiogenic
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medicine
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non-anticoagulant
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iduronic
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sdc1
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prometastatic
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chondroitinase
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intrachain
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drug development
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tfpi-2
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analysis
- 3.2.1.166
- metastasis
- proteoglycans
- angiogenesis
- endothelial
- heparin
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endoglycosidase
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basement
- glycosaminoglycans
- melanoma
- vessel
- oligosaccharide
- platelet
- syndecan-1
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hspgs
- node
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angiogenic
- myeloma
- nephropathy
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anticoagulant
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glycocalyx
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clinicopathological
- metalloproteinases
- glomerular
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procoagulant
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heparin-binding
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antimetastatic
- heparinase
- neovascularization
- fgf-2
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extravasation
- bfgf
- perlecan
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subendothelial
- matrigel
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microvessel
- chondroitin
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pro-tumorigenic
-
o-sulfation
-
matrix-degrading
- vegf-c
- pharmacology
-
glypicans
- diagnostics
-
proangiogenic
- medicine
-
non-anticoagulant
-
iduronic
- sdc1
-
prometastatic
- chondroitinase
-
intrachain
- drug development
-
tfpi-2
- analysis
Reaction
endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan =
Synonyms
BpHep, C1A heparanase, endo-beta-D-glucuronidase, endo-beta-glucuronidase, heparan sulfate glycosidase, heparanase, heparanase 1, heparanase-1, HPA, Hpa1, Hpa1 heparanase, HPSE, T5
ECTree
3.2.1.166 heparanaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 3.2.1.166 - heparanase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(1H-benzo[d]imidazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis-(methylene))diboronic acid
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(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis(3-methylbutane-1,1-diyl))diboronic acid
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(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis-(methylene))diboronic acid
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(2E)-N-(3,4-dichlorophenyl)-3-[3-fluoro-4-[5-(2-oxopropyl)-1,3-benzoxazol-2-yl]phenyl]prop-2-enamide
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(3S,4S,5R,6R)-4,5-dihydroxy-6-[(trifluoroacetyl)amino]piperidine-3-carboxylic acid
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(IdoA2S-GlcNS)n
polysaccharide containing IdoA2S-GlcNS repeating unit, inhibits the activity of heparanase
1-[2-([3-[(7-chloroquinolin-4-yl)amino]-5-(hydroxymethyl)benzyl]amino)prop-2-en-1-yl]piperidin-4-ol
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1-[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzyl]piperidin-4-ol
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2,2'-((((carbonylbis(azanediyl))bis(4,1-phenylenesulfonyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
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2,2'-((((Iminomethylene)bis(azanediyl))bis(4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid
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2,2'-(((4,4'-(2-hydroxypropane-1,3-diyl)bis(benzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
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2,2'-(((4,4'-(2-oxopropane-1,3-diyl)bis(benzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
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2,2'-(((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-bis(3,1-phenylene))diacetic acid
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2,2'-(((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-bis(4-hydroxy-3,1-phenylene))diacetic acid
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2,2'-(((4,4'-(thiocarbonylbis(azanediyl))bis(3-fluorobenzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
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2,2'-(((carbonylbis(azanediyl))bis(3,1-phenylene))bis(benzo[d]-oxazole-2,5-diyl))diacetic acid
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2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(1H-benzo[d]imidazole-2,5-diyl))diacetic acid
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2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(N-isopentylacetamide)
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2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid
causes inhibition of the proliferation of human CME-1 synovial sarcoma cells
2,2'-(((carbonylbis(azanediyl))bis(4,1-phenylene))bis(benzo[d]-oxazole-2,5-diyl))diacetic acid
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2,2'-(((carbonylbis(azanediyl))bis(piperidine-4,1-diyl))bis(benzo-[d]oxazole-2,5-diyl))diacetic acid
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2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))-bis(1H-benzo[d]imidazole-2,5-diyl))diacetic acid
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2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))-bis(benzo[d]oxazole-2,5-diyl))diacetic acid
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2,2'-(((thiocarbonylbis(azanediyl))bis(4,1-phenylene))bis(benzo-[d]oxazole-2,5-diyl))diacetic acid
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2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(1H-benzo[d]imidazole-2,5-diyl))bis(acetyl))bis-(azanediyl))bis(3-phenylpropanoic acid)
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2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))bis(3-phenylpropanoic acid)
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2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid
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2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))dipropionic acid
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2,2'-((2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid
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2-(3-(4-(3-(4-((5-(carboxymethyl)-2-hydroxyphenyl)carbamoyl)-phenyl)-2-hydroxypropyl)-3-hydroxybenzamido)phenyl)acetic acid
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2-[(3-[4-[3-(4-chloro-2-cyclohexylphenoxy)-5-nitrophenoxy]phenyl]propanoyl)amino]ethanesulfonic acid
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2-[2-methoxy-5-(5-phenyl-1,3-benzoxazol-2-yl)-4-(propylamino)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
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2-[3-(1,3-benzoxazol-2-yl)phenyl]-1,3-dioxo-2,3-dihydro-1H-indene-5-carboxylic acid
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2-[3-[5-(4-chlorophenyl)-1,3-benzoxazol-2-yl]-4-(propylamino)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
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2-[3-[5-(4-fluorophenyl)-1,3-benzoxazol-2-yl]-4-(propylamino)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
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2-[4-[4-(6-amino-1H-benzimidazol-2-yl)phenoxy]phenyl]-1H-benzimidazol-5-amine
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3,3'-((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-dibenzoic acid
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3-[(7-chloroquinolin-4-yl)amino]-N-[2-(dimethylamino)ethyl]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzamide
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3-[(7-chloroquinolin-4-yl)amino]-N-[2-(morpholin-4-yl)ethyl]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzamide
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4-[(4-carboxy-3-hydroxy-5-methylphenoxy)carbonyl]-3-hydroxy-5-pentadecylphenyl beta-D-glucopyranosiduronic acid
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4-[(4-carboxy-3-hydroxy-5-methylphenoxy)carbonyl]-3-hydroxy-5-pentadecylphenyl methyl beta-D-glucopyranosiduronate
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4-[[5-(3,6-dibromo-9H-fluoren-9-yl)-4-hydroxy-2-(2-phenylethyl)pentanethioyl]amino]benzenesulfonic acid
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5-bromo-2-hydroxy-N-[(E)-(3-[2-[(4-methylphenyl)amino]-2-oxoethyl]-2-oxo-2,3-dihydro-1H-inden-1-ylidene)methyl]benzamide
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5-[2-[4-([4-[(3-bromo-4-methoxybenzoyl)amino]benzyl]amino)-3-fluorophenyl]-1H-benzimidazol-5-yl]-4-oxopentanoic acid
i.e. SST0871AA1
5-[3-(2-methylidenenonadecyl)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-2-phenoxybenzenesulfonic acid
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7-chloro-N-[3-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]oxy]methyl)phenyl]quinolin-4-amine
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7-chloro-N-[3-[(diethylamino)methyl]-4-(morpholin-4-yl)phenyl]quinolin-4-amine
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defibrotide
a polydisperse oligonucleotide isolated from porcine mucosa that has multiple biological effects including inhibition of heparanase gene expression and enzymatic activity
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heparanase inhibitor PI-88
a mixture of highly sulfated, monophosphorylated mannose oligosaccharides, derived from the extracellular phosphomannan of the yeast Pichia holstii, with potential antiangiogenic activity
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M402
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a glycol-split heparin compound similar to SST0001 yet smaller in molecular mass
maltohexaose sulfate
with at least 3 sulfate groups per internal sugar and up to four sulfates in the terminal sugar residues, docking sstudy and binding structure, overview
N'-[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzyl]-N,N-dimethylethane-1,2-diamine
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N-[4-([[4-(1H-benzimidazol-2-yl)phenyl]amino]methyl)phenyl]-3-bromo-4-methoxybenzamide
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N-[4-([[5-(1H-benzimidazol-2-yl)pyridin-2-yl]amino]methyl)phenyl]-3-bromo-4-methoxybenzamide
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necuparanib
formally M402, an N-sulfated glycol-split heparin of 6 kDa, shows efficacy in metastasis models
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oligomannurarate sulfate
the heparanase inhibitor simultaneously targets basic fibroblast growth factor, combats tumor angiogenesis and metastasis. The inhibitor is a promising candidate agent for cancer therapy
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oligomanurarate sulfate
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JG3, a marine-derived oligosaccharide and a heparanase inhibitor
PG545 cholestanol aglycon
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the cholestanol aglycon of PG545 significantly increased affinity for heparanase and also modified the inhibition mode, parabolic competition
sodium octyl 4-O-[2-deoxy-2-(sulfoamino)-alpha-D-glucopyranosyl]-beta-D-glucopyranosiduronate
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specific inhibition
[2-(4-[[(2E)-3-(4-bromophenyl)prop-2-enoyl]amino]phenyl)-1,3-benzoxazol-5-yl]acetic acid
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[2-[4-([4-[(3-bromo-4-methoxybenzoyl)amino]benzyl]amino)-3-fluorophenyl]-1H-benzimidazol-5-yl]acetic acid
i.e. SST0867AA1
[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(morpholin-4-yl)prop-1-en-2-yl]amino]methyl)phenyl]methanol
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[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)phenyl](morpholin-4-yl)methanone
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[4-(5-[2-chloro-4-[(4-chlorobenzoyl)amino]phenyl]furan-2-yl)-1,3-thiazol-2-yl]acetic acid
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[4-[5-(4-[[(2E)-3-(4-bromophenyl)prop-2-enoyl]amino]-2-chlorophenyl)furan-2-yl]-1,3-thiazol-2-yl]acetic acid
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heparin
commercial heparin is a powerful inhibitor of heparanase action toward antithrombin-binding oligosaccharides
heparin
heparin-binding domains HBD-1 and HBD-2 in heparanase, structure overview. The optimal length of a heparin chain required to bridge HBD-1 and HBD-2 for the effective inhibition is known to be an octadecasaccharide, whereas heparin tetrasaccharides and hexasaccharides as well as N-acetylated heparins (N-acetylation higher than 50%) are poor inhibitors of heparanase
PG545
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a synthetic, potent competitive inhibitor of heparanase with significant anti-tumor, anti-angiogenic, and anti-metastatic activity in a variety of animal models
PG545
a fully sulfated synthetic tetrasaccharide functionalized with a cholestanyl aglycon
PI-88
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inhibits primary tumor growth of invasive rat mammary adenocarcinoma, metastasis, and reduced vascularity of these tumors while demonstrating significant anti-tumor activity in the pancreatic neuroendocrine RIP2-Tag2 model and in models of leukemia
roneparstat
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is an N-acetylated, glycol-splitheparin,which inhibits heparanase, downregulates HGF, VEGF, and MMP-9 expression and suppresses angiogene-sis. Roneparstat also diminishes heparanase-induced shedding of syndecan-1, which is known to be a potent promoter of myeloma
roneparstat
SST0001, an N-acetylated glycol-split heparin and a potent inhibitor of heparanase, consists of a chemically modified heparin (reduced oxidized N-acetylated heparin) that is non-anticoagulant and is not degraded by the enzyme. In a model of dexamethasone resistant MM, the combination of Roneparstat with dexamethasone inhibits tumor growth. Roneparstat dramatically reduces tumor growth in bone when used in combination with either bortezomib or melphalan
additional information
the PG500 series of heparan sulfate mimetics potently block the enzymatic activity of heparanase (fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development)
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additional information
a simple, accurate, and robust biochemical assay for heparanase activity that uses a commercially available homogeneous substrate (fondaparinux) with a single enzymatic cleavage point and, thus, does not have the problems associated with using heparan sulfate-based assays. The assay is suitable for testing heparanase inhibitors and could easily be adapted for use in high-throughput screening applications
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additional information
polysacchride with repeating disaccharide units of GlcA-GlcNAc or polysaccharide with repeating units of GlcA-GlcNAc6S do not inhibit activity of heparanase
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additional information
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the full-length heparanase 2c protein inhibits heparanase enzymatic activity, likely due to its high affinity to heparin and heparan sulfate and its ability to associate physically with heparanase
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additional information
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screening of a virtual inhibitor library composed of 27 known heparanase inhibitors and a commercial collection of drugs and drug-like compounds, overview. A subset of fourteen 4-arylaminoquinolines from a global set of 249 analogues of amodiaquine is selected based on the application of in silico models, a QSAR solubility prediction model and a chemical diversity analysis. Some of these compounds displayed binding affinities in the micromolar range. Structure-activity relationships around the amodiaquine scaffold, overview
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additional information
the natural heparan sulfate-heparanase interactions are used as a template for the design of heparan sulfate-mimicking glycopolymers, e.g. saccharide-functionalized neo-glycopolymers, which retain the key biological properties of the natural polysaccharides, synthesis and mass spectrometric identification, detailed overview. A glycopolymer with 12 repeating units is determined to be the most potent inhibitor and to have tight-binding characteristics. This glycopolymer also lacks anticoagulant activity. Inhibition of heparanase by HS mimicking monomers and neo-glycopolymers using TR-FRET assay
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additional information
heparanase inhibitors used in tandem with chemotherapeutic drugs overcome initial chemoresistance. Heparin-like compounds that inhibit heparanase activity are being evaluated in clinical trials for various types of cancer. Heparanase-inhibiting small molecules are developed based on the recently resolved crystal structure of the heparanase protein. Heparanase neutralizing monoclonal antibodies have been generated and found effective in preclinical cancer models
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additional information
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heparanase inhibitors used in tandem with chemotherapeutic drugs overcome initial chemoresistance. Heparin-like compounds that inhibit heparanase activity are being evaluated in clinical trials for various types of cancer. Heparanase-inhibiting small molecules are developed based on the recently resolved crystal structure of the heparanase protein. Heparanase neutralizing monoclonal antibodies have been generated and found effective in preclinical cancer models
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additional information
symmetrical benzazolyl derivatives show potent anti-heparanase activity, synthesis, and molecular docking studies, overview. The anti-metastatic potential of compounds 2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid, 2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid, and 2,2'-((2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid, proves the inhibition of the expression of proangiogenic factors in tumor cells. Molecular modeling of inhibitor binding and mechanism
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