Information on EC 3.4.24.82 - ADAMTS-4 endopeptidase

New: Word Map on EC 3.4.24.82
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY hide
3.4.24.82
-
RECOMMENDED NAME
GeneOntology No.
ADAMTS-4 endopeptidase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Glutamyl endopeptidase; bonds cleaved include -Thr-Glu-Gly-Glu373-/-Ala-Arg-Gly-Ser- in the interglobular domain of mammalian aggrecan
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
147172-61-0
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Mus musculus C3H/HEN
strain C3H/HEN
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
the lack of hevin cleavage, as seen in ADAMTS4-null mice results in altered Purkinje-cell morphology and a reactive gliosis phenotype in the brain of these adult animals
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Abz-TEGEARGSVI-Dap(2,4-dinitrophenyl)-KK + H2O
?
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
?
show the reaction diagram
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
aggrecan + H2O
G1-NITEGE374 + ?
show the reaction diagram
-
assay at pH 7.5, 16 h, 37C, 100 nM ADAMTS4, reaction stopped by addition of Na acetate, Tris and EDTA
-
-
?
aggrecan-interglobular domain + H2O
?
show the reaction diagram
biglycan + H2O
?
show the reaction diagram
brevican + H2O
?
show the reaction diagram
brevican + H2O
fragments of brevican
show the reaction diagram
C6-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-Gly-Thr-Lys(Mca)-Gly-Glu-Leu-Glu-Gly-Arg-Gly-Thr-Lys(Dnp)-Gly-Ile-Ser-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
carboxyfluorescein-AELQGRPISIAK-N,N,N',N'-tetramethyl-6-carboxyrhodamine + H2O
carboxyfluorescein-AE + LQGRPISIAK-N,N,N',N'-tetramethyl-6-carboxyrhodamine
show the reaction diagram
-
-
-
-
?
carboxyfluorescein-Ala-Glu-Leu-Asn-Gly-Arg-Pro-Ile-Ser-Ile-Ala-Lys-N,N,N',N'-tetramethyl-6-carboxyrhodamine + H2O
carboxyfluorescein-Ala-Glu + Leu-Asn-Gly-Arg-Pro-Ile-Ser-Ile-Ala-Lys-N,N,N',N'-tetramethyl-6-carboxyrhodamine
show the reaction diagram
-
-
-
-
?
carboxymethylated transferrin + H2O
?
show the reaction diagram
cartilage disc extract supernantant + H2O
hyaluron + hyaladherins
show the reaction diagram
-
-
-
-
?
cartilage oligomeric matrix protein + H2O
?
show the reaction diagram
-
-
-
-
?
chondroitin 4-sulfate + H2O
?
show the reaction diagram
-
-
-
-
?
decorin + H2O
?
show the reaction diagram
DVQEFRGVTAVIR + H2O
?
show the reaction diagram
-
-
-
-
?
FAM-AELQGRPISIAK-TAMRA + H2O
?
show the reaction diagram
-
activity measured using a quenched fluorescent substrate
-
-
?
fibromodulin + H2O
?
show the reaction diagram
Fibronectin + H2O
?
show the reaction diagram
-
-
-
-
?
hevin + H2O
?
show the reaction diagram
-
digestion of hevin by ADAMTS4 in vitro produces fragments similar to those present in brain lysates. The proteolysis liberates a hevin peptide, termed SPARC-like fragment, with significant homology to SPARC (secreted protein acidic and rich in cysteine)
-
-
?
HNEFRQRETYMVF + H2O
?
show the reaction diagram
-
-
-
-
?
K(6-(fluorescein-5-carboxamido)-hexanoic acid)-DVQEFRGVTAVIR-C(QSY9)-KGK + H2O
C(QSY9) + KGK + K(6-(fluorescein-5-carboxamido)-hexanoic acid)-DVQEFRGVTAVIR
show the reaction diagram
-
-
-
-
?
Lys(7-methoxycoumarin-4-yl)-Lys-Gln-Glu-Phe-Arg-Gly-Gln-Thr-Lys(Dnp)-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Lys(carboxyfluorescein)-Asp-Val-Gln-Glu-Phe-Arg-Gly-Val-Thr-Ala-Val-Ile-Arg-Lys(tetramethylrhodamine)-Lys-Gly-Lys-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
matrilin-2 + H2O
?
show the reaction diagram
-
-
substrate contains two putative cleavage sites. The first site is located between residues D851 and L852 in the middle of the domain and the second at the boundary with the coiled-coil domain at the C-terminus. Deletion of the entire unique domain eliminates the proteolysis of matrilin-2. The first cleavage site is present in all matrilin-2 oligomers, the second cleavage site becomes apparent only in the matrilin-2 hetero-oligomers with matrilin-1 or matrilin-3
-
?
matrilin-3 + H2O
?
show the reaction diagram
-
cleaves at Glu435/Ala436 generating two species of 45 and 5 kDa
-
-
?
N-procollagen + H2O
?
show the reaction diagram
-
-
-
-
?
neurocan + H2O
?
show the reaction diagram
-
-
-
-
?
phosphacan + H2O
?
show the reaction diagram
-
-
-
-
?
QTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLK + H2O
QTVTWPDMELPLPRNITEGE + ARGSVILTVKPIFEVSPSPLK
show the reaction diagram
-
-
-
?
recombinant Agg1 + H2O
fragments of recombinant Agg1
show the reaction diagram
transferrin + H2O
?
show the reaction diagram
-
-
-
-
?
versican + H2O
?
show the reaction diagram
-
-
-
-
?
versican + H2O
fragments of versican
show the reaction diagram
-
both ADAMTS-1 and ADAMTS-4 cleave native human and recombinant versican at Glu441-A442, ADAMTS-4 is 5-10fold more active than ADAMTS-1
-
?
versican V1 + H2O
fragments of versican V1
show the reaction diagram
-
-
-
-
?
versican V2 + H2O
glial hyaluronate binding protein + ?
show the reaction diagram
-
-
-
-
?
versican-1 + H2O
?
show the reaction diagram
-
-
-
-
?
versican-2 + H2O
?
show the reaction diagram
-
-
-
-
?
VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG + H2O
?
show the reaction diagram
-
43mer peptide substrate
-
-
?
[C6-(Gly-Pro-Hyp)5-Gly-Thr-Lys(7-amido-4-methylcoumarin)-Gly-Glu-Leu-Glu-Gly-Arg-Gly-Thr-Lys(2,4-dinitrophenyl)-Gly-Ile-Ser-(Gly-Pro-Hyp)5-NH2]3 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
aggrecan + H2O
?
show the reaction diagram
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
brevican + H2O
fragments of brevican
show the reaction diagram
-
-
-
-
?
carboxymethylated transferrin + H2O
?
show the reaction diagram
-
-
-
-
?
cartilage oligomeric matrix protein + H2O
?
show the reaction diagram
-
-
-
-
?
decorin + H2O
?
show the reaction diagram
-
-
-
-
?
fibromodulin + H2O
?
show the reaction diagram
-
-
-
-
?
versican V1 + H2O
fragments of versican V1
show the reaction diagram
-
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
Ca2+-dependent metalloproteinase
Zn2+
-
contains a zinc catalytic domain
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R)-2-(biphenyl-4-ylsulfonyl)-3-(1H-indol-2-yl)propanoic acid
-
IC50: 0.0028 mM
(2R)-2-(biphenyl-4-ylsulfonyl)-3-phenylpropanoic acid
-
IC50: 0.0043 mM
(2R)-2-(biphenyl-4-ylsulfonyl)pentanedioic acid
-
IC50: 0.0011 mM
(2R)-2-(biphenyl-4-ylsulfonyl)propanoic acid
-
IC50: 0.0055 mM
(2R)-2-([[3'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
-
(2R)-2-([[3'-(aminomethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
-
(2R)-2-([[3'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
-
(2R)-2-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
-
(2R)-2-([[4'-(carbamoyloxy)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
-
(2R)-2-([[4'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
-
(2R)-2-[(biphenyl-4-ylsulfonyl)amino]-3-methylbutanoic acid
-
-
(2R)-2-[[(3'-carbamoylbiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
-
(2R)-2-[[(3'-cyanobiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
-
(2R)-2-[[(3'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
-
(2R)-2-[[(4'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
-
(2R)-3-methyl-2-[([4'-[(methylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)amino]butanoic acid
-
-
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
(2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide
-
-
(2R,5R)-1-([4-[(5-fluoro-2-methylbenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxypiperidine-2-carboxamide
-
IC50: 145 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 2.1 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 16 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-chloro-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 0.5 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-ethylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 67 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-isopropylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
78% inhibition of enzyme activity at 500 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-3-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 3.9 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 2.7 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-5-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 40 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 38 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(3-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
57% inhibition of enzyme activity at 500 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(3-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 100 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(3-methylisothiazol-4-yl)methoxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
76% inhibition of enzyme activity at 500 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(4-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 100 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(4-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
19% inhibition of enzyme activity at 500 nM
(2R,5R)-N,5-dihydroxy-1-([4-[(4-methylisothiazol-5-yl)methoxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
55% inhibition of enzyme activity at 500 nM
(2R,5R)-N,5-dihydroxy-1-[[4-(2-chloropyridin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 18 nM
(2R,5R)-N,5-dihydroxy-1-[[4-(2-methylpyridin-3-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 91 nM
(2R,5R)-N,5-dihydroxy-1-[[4-(isoquinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 100 nM
(2R,5R)-N,5-dihydroxy-1-[[4-(quinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 15 nM
(2S,3R)-2-[(cyclopropylmethyl)amino]-N1-hydroxy-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-methylbutanediamide
-
the reduced pattern of H-bond interactions is suitable for the flexible environment of ADAMTS4 and ADAMTS5 since it enables the inhibitor to re-optimizing its interaction pattern step-by-step, following the loop motion. The conformational flexibility observed for the S1' loop of ADAMTS4 and ADAMTS5 seems to be correlated to the motion of the TS-domain
(3R)-N2-(cyclopropylmethyl)-N1-hydroxy-3-(3-hydroxybenzyl)-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-L-aspartamide
-
-
(E)-4-[2-(3,5-dihydroxyphenyl)ethenyl]1,2-benzenediol
-
i.e. piceatannol
(R)-2-(3-fluoro-4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
(R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
2-deoxyfluoroglucose
-
0.01 mM
2-[4-(benzyloxy)phenyl]-2,3-dihydro-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxylate
-
the inhibitor is unable to discriminate between ADAMTS-5 and ADAMTS-4
2-[4-(benzyloxy)phenyl]-2,3-dihydro-N-hydroxy-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxamide
-
-
3-[(biphenyl-4-ylsulfonyl)amino]-4-methylpentanoic acid
-
IC50: 0.1 mM
3-[[(4'-[[(1R)-1-carboxy-2-methylpropyl]sulfamoyl]biphenyl-4-yl)oxy]methyl]benzoic acid
-
-
acetyl-DVQEFRGVTAVIRNH2
-
-
acetyl-HNEFRQRETYMVF-NH2
-
-
actinonin
-
0.01 mg/ml, 61% inhibition
AG3340
AG490
-
0.01 mM
alpha2-Macroglobulin
-
-
-
batimastat
-
-
BB94
-
0.000524 mM, 85% inhibition, hydroxamate-based matrix metalloproteinase inhibitor
C-terminal 40-kDa fibronectin fragment
-
wild type enzyme IC50: 170 nM, complete inhibition at 750 nM
-
calcium pentosan polysulfate
-
no impact on gene expression, but directly inhibit the aggrecanase activity
-
chondroitin 6-sulfate
-
-
chondroitin sulfate
-
-
CT-1746
-
0.000048 mM, 50% inhibition, hydroxamate-based matrix metalloproteinase inhibitor
-
D-mannosamine
-
1.5 mM
dermatan sulfate
-
-
doxycycline
-
dose-dependently inhibits the activity of rhADAMTS4 in vitro
DPC
-
non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 10 nM
EGTA
-
5 mM, complete inhibition
enoxaparin
-
-
fibronectin
GGWGPWGPWGD
-
peptide representing the N-terminal region of the aggrecane TPS-1 motif containign the GAG binding motif, 0.017 mM, 50% inhibition
-
GGWGPWGPWGDCSRTCGGG
-
peptide containing both the GAG and CD36 binding motifs of aggrecan, 0.003 mM, 50% inhibition
-
glycosaminoglycan
-
-
heparan sulfate
-
-
heparin
hyaluronan
-
hyaluronan 800 kDA and 2700 kDa decreased IL1alpha-induced expression of aggrecanase-1 decreased
Interleukin-1beta
-
lower mRNA level of aggrecan
-
Janus kinase 2 inhibitor
-
10 g/ml
-
Janus kinase 3 inhibitor
-
30 g/ml
-
KB-R7785
-
-
Keratan sulfate
-
-
LY294002
-
0.01 mM, reduces ADAMTS-4 expression
marimastat
minocycline
-
dose-dependently inhibits the activity of rhADAMTS4 in vitro
N-(biphenyl-3-ylsulfonyl)-D-valine
-
IC50: 0.1 mM
N-(biphenyl-4-ylsulfonyl)-D-valine
-
IC50: 0.003 mM
N-(biphenyl-4-ylsulfonyl)-L-valine
-
IC50: 0.1 mM
N-(biphenyl-4-ylsulfonyl)-N-(pyridin-3-ylmethyl)-D-valine
-
IC50: 0.012 mM
N-(biphenyl-4-ylsulfonyl)-N-methyl-D-valine
-
IC50: 0.0016 mM
N-([3'-[(acetylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(1-benzofuran-2-ylcarbonyl)amino]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.0075 mM
N-([4'-[(1-benzofuran-2-ylcarbonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.00035 mM
N-([4'-[(2-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(2-methylpyridin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(2-methylquinolin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(3-bromobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(3-chlorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(3-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(3-fluorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(3-hydroxybenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(3-nitrobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(4-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(benzoylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(benzylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(furan-2-yloxy)carbonyl]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.0116 mM
N-([4'-[(phenylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(phenylsulfonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
-
N-([4'-[(Z)-2-(1-benzofuran-2-yl)ethenyl]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.0004 mM
N-([4'-[2-(1-benzofuran-2-yl)-2-oxoethyl]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.0038 mM
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
all isoforms of ADAMTS-4 are effectively inhibited. Inhibited more strongly by N-terminal domain of tissue inhibitor of metalloproteinases-3 than by full-length tissue inhibitor of metalloproteinases-3
-
N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3
-
N-terminal mutants of N-TIMP-3 (tissue inhibitor of metalloproteinases 3) that have lost their matrix metalloproteinase P-inhibitory activities (N-TIMP-3(T2G)and [-1A]N-TIMP-3), retain their ability to inhibit ADAMTS-4 and ADAMTS-5. The [-2A]N-TIMP-3 mutant also retains strong affinity with ADAMTS-5, but has a lower affinity for ADAMTS-4 and ADAM17
-
N-[(2'-aminobiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.05 mM
N-[(2'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.02 mM
N-[(2-aminobiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.03 mM
N-[(3'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.009 mM
N-[(4'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.0046 mM
N-[(4'-phenoxybiphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[1-[3-(trifluoromethyl)phenyl]ethoxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[(3-methyl-1-benzofuran-2-yl)carbonyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.000086 mM
N-[(4'-[[(3-methyl-1-benzofuran-2-yl)oxy]methyl]biphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.0007 mM
N-[(4'-[[2-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[2-(trifluoromethyl)pyridin-4-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[3-(methoxycarbonyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[3-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[4-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[6-(trifluoromethyl)pyridin-2-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[(4'-[[acetyl(methyl)amino]methyl]biphenyl-4-yl)sulfonyl]-D-valine
-
-
N-[[(4S)-4-(1-methylimidazol-2-yl)-2,5-dioxo-imidazolidin-4-yl]methyl]-5-(trifluoromethyl)benzofuran-2-carboxamide
-
inhibitor has excellent selectivity over other zinc metalloproteases such as TACE, MMP2, MMP3, MMP13, and MMP14
N-[[4'-(1-benzofuran-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
IC50: 0.0014 mM
N-[[4'-(benzyloxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(cyclohexylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(naphthalen-1-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(naphthalen-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(pyridin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(pyridin-3-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(pyridin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(quinolin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N-[[4'-(quinolin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
-
N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine
-
-
NL-71-101
-
0.02 mM, reduces ADAMTS-4 expression
o-phenanthroline
-
1 mM, complete inhibition of aggrecanase 1 and 2
parthenolide
-
0.005 mM, reduces ADAMTS-4 expression
PD98059
-
inhibition of MAP kinase signaling pathway result in inhibition of neurite outgrowth induced by ADAMTS4
phosphatidylinositol 3-kinase
-
reduces ADAMTS-4 expression
-
pyrogallol
-
-
QEYKAHHSYKLMS
-
-
SC81956
tetracycline
-
dose-dependently inhibits the activity of rhADAMTS4 in vitro
TIMP-3
-
-
-
TIMP3
-
-
-
tinzaparin
-
-
-
tissue inhibitor of matrix metalloproteinases-3
-
TIMP-3
-
Tissue inhibitor of metalloproteinase-1
-
150 nM or 270 nM
-
tissue inhibitor of metalloproteinases 3
tissue inhibitor of metalloproteinases-3
Tripterygium wilfordii Hook F extract
-
-
-
triptolide
-
600 nM, PG490
U0126
-
inhibition of MAP kinase signaling pathway result in inhibition of neurite outgrowth induced by ADAMTS4
XS309
-
0.002185 mM, 50% inhibition
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
C-terminal thrombospondin type I motif of ADAMTS-5
-
addition of the C-terminal thrombospondin type I motif of ADAMTS-5 to the C terminus of ADAMTS-4 increases the activity of ADAMTS-4 against aggrecan and fibromodulin severalfold
-
glycosylphosphatidyl inositolanchored membrane type 4-matrix metalloproteinase
-
MT4-MMP or also called MMP-17
-
IL-1beta
-
10 ng/ml, 20 min, upregulation of ADAMTS-4 only in presence of adaptor proteins MyD88, IRAK1 and TRAF6
-
interferon gamma
-
-
-
interleukin-1
interleukin-1alpha
Interleukin-1beta
-
10 ng/ml
-
NaCl
-
the optimum NaCl concentration for aggrecan degradation is between 12.5 and 50 mM
NFkappaB
oncostatin M
retinoic acid
-
-
syndecan-1
-
proteoglycan form of syndecan-1
-
tissue necrosis factor alpha
-
-
-
TNF-alpha
-
10 ng/ml
-
transforming growth factor beta
Tumor necrosis factor alpha
tumour necrosis factor
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0203
Aggrecan
-
in 100 mM NaCl
-
0.279 - 0.761
C6-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-Gly-Thr-Lys(Mca)-Gly-Glu-Leu-Glu-Gly-Arg-Gly-Thr-Lys(Dnp)-Gly-Ile-Ser-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-NH2
0.0282
chondroitin 4-sulfate
-
in 100 mM NaCl
0.035
Lys(carboxyfluorescein)-Asp-Val-Gln-Glu-Phe-Arg-Gly-Val-Thr-Ala-Val-Ile-Arg-Lys(tetramethylrhodamine)-Lys-Gly-Lys-NH2
-
pH 7.5, 37C
0.48
QTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLK
-
biotinylated peptide containing aggrecanase cleavage site
0.0471 - 0.65
[C6-(Gly-Pro-Hyp)5-Gly-Thr-Lys(7-amido-4-methylcoumarin)-Gly-Glu-Leu-Glu-Gly-Arg-Gly-Thr-Lys(2,4-dinitrophenyl)-Gly-Ile-Ser-(Gly-Pro-Hyp)5-NH2]3
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.49
Aggrecan
Homo sapiens
-
in 100 mM NaCl
-
0.072 - 0.433
C6-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-Gly-Thr-Lys(Mca)-Gly-Glu-Leu-Glu-Gly-Arg-Gly-Thr-Lys(Dnp)-Gly-Ile-Ser-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-NH2
1.16
chondroitin 4-sulfate
Homo sapiens
-
in 100 mM NaCl
0.012 - 0.181
[C6-(Gly-Pro-Hyp)5-Gly-Thr-Lys(7-amido-4-methylcoumarin)-Gly-Glu-Leu-Glu-Gly-Arg-Gly-Thr-Lys(2,4-dinitrophenyl)-Gly-Ile-Ser-(Gly-Pro-Hyp)5-NH2]3
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000065
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
-
or above, pH not specified in the publication, temperature not specified in the publication
0.000003
(2S,3R)-2-[(cyclopropylmethyl)amino]-N1-hydroxy-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-methylbutanediamide
-
or above, pH not specified in the publication, temperature not specified in the publication
0.00268 - 0.00506
(E)-4-[2-(3,5-dihydroxyphenyl)ethenyl]1,2-benzenediol
0.0453 - 0.0611
doxycycline
0.00008
enoxaparin
-
-
0.000105
GGWGPWGPWGDCSRTCGGG
-
-
-
0.000079
marimastat
-
pH not specified in the publication, temperature not specified in the publication
0.0869 - 0.0973
minocycline
0.0001 - 0.00064
N-terminal domain of tissue inhibitor of metalloproteinases-3
0.00634 - 0.041
pyrogallol
0.026
QEYKAHHSYKLMS
-
at 37C
0.0000228
SC81956
-
at 37C
0.12 - 0.761
tetracycline
0.0000079
TIMP-3
-
-
-
0.00002
tinzaparin
-
-
-
0.0000033
tissue inhibitor of matrix metalloproteinases-3
-
-
-
0.00022 - 0.00051
tissue inhibitor of metalloproteinases-3
additional information
additional information
-
Ki(app) of N-terminal alanine-extension mutants and of position [-1] mutants of N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028
(2R)-2-(biphenyl-4-ylsulfonyl)-3-(1H-indol-2-yl)propanoic acid
Rattus norvegicus
-
IC50: 0.0028 mM
0.0043
(2R)-2-(biphenyl-4-ylsulfonyl)-3-phenylpropanoic acid
Rattus norvegicus
-
IC50: 0.0043 mM
0.0011
(2R)-2-(biphenyl-4-ylsulfonyl)pentanedioic acid
Rattus norvegicus
-
IC50: 0.0011 mM
0.0055
(2R)-2-(biphenyl-4-ylsulfonyl)propanoic acid
Rattus norvegicus
-
IC50: 0.0055 mM
0.02
(2R)-2-([[3'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
Homo sapiens
-
IC50 around 0.02 mM, pH and temperature not specified in the publication
0.0072
(2R)-2-([[3'-(aminomethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0021
(2R)-2-([[3'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.1
(2R)-2-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
Homo sapiens
-
IC50 around 0.1 mM, pH and temperature not specified in the publication
0.00042 - 0.0041
(2R)-2-([[4'-(carbamoyloxy)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
0.015
(2R)-2-([[4'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.003
(2R)-2-[(biphenyl-4-ylsulfonyl)amino]-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0084
(2R)-2-[[(3'-carbamoylbiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.04
(2R)-2-[[(3'-cyanobiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.009
(2R)-2-[[(3'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0046
(2R)-2-[[(4'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.05
(2R)-3-methyl-2-[([4'-[(methylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)amino]butanoic acid
Homo sapiens
-
IC50 around 0.05 mM, pH and temperature not specified in the publication
0.000065
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
Homo sapiens
-
pH 7.5, 37C
0.0000011
(2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide
Homo sapiens
-
37C, pH and temperature not specified in the publication
0.000145
(2R,5R)-1-([4-[(5-fluoro-2-methylbenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxypiperidine-2-carboxamide
Homo sapiens
-
IC50: 145 nM
0.0000021
(2R,5R)-N,5-dihydroxy-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 2.1 nM
0.000016
(2R,5R)-N,5-dihydroxy-1-([4-[(2-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 16 nM
0.0000005
(2R,5R)-N,5-dihydroxy-1-([4-[(2-chloro-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 0.5 nM
0.000067
(2R,5R)-N,5-dihydroxy-1-([4-[(2-ethylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 67 nM
0.0000039
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-3-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 3.9 nM
0.0000027
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 2.7 nM
0.00004
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-5-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 40 nM
0.000038
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
Homo sapiens
-
IC50: 38 nM
0.0001
(2R,5R)-N,5-dihydroxy-1-([4-[(3-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
0.000018
(2R,5R)-N,5-dihydroxy-1-[[4-(2-chloropyridin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
Homo sapiens
-
IC50: 18 nM
0.000091
(2R,5R)-N,5-dihydroxy-1-[[4-(2-methylpyridin-3-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
Homo sapiens
-
IC50: 91 nM
0.0001
(2R,5R)-N,5-dihydroxy-1-[[4-(isoquinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
Homo sapiens
-
IC50: 100 nM
0.000015
(2R,5R)-N,5-dihydroxy-1-[[4-(quinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
Homo sapiens
-
IC50: 15 nM
0.000003
(3R)-N2-(cyclopropylmethyl)-N1-hydroxy-3-(3-hydroxybenzyl)-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-L-aspartamide
Homo sapiens
-
pH 7.5, 37C
0.00018
(R)-2-(3-fluoro-4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0002
(R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0049
(R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.001
(R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.00023
(R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0012
(R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0011
(R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0018
(R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.00008
(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.00009
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.00059
(R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.00043
(R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0017
(R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0001
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0016
(R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0002
(R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.00073
(R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0052
(R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.006
(R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0009
(R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0019
(R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0004
(R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0008
(R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.02
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0032
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.00023
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.0004
(R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
0.015
2-[4-(benzyloxy)phenyl]-2,3-dihydro-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxylate
Homo sapiens
-
37C, pH and temperature not specified in the publication
0.00021
2-[4-(benzyloxy)phenyl]-2,3-dihydro-N-hydroxy-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxamide
Homo sapiens
-
37C, pH and temperature not specified in the publication
0.1
3-[(biphenyl-4-ylsulfonyl)amino]-4-methylpentanoic acid
Rattus norvegicus
-
IC50: 0.1 mM
0.022
3-[[(4'-[[(1R)-1-carboxy-2-methylpropyl]sulfamoyl]biphenyl-4-yl)oxy]methyl]benzoic acid
Homo sapiens
-
IC50 around 0.022 mM, pH and temperature not specified in the publication
0.00012
AG3340
Bos taurus
-
non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 120 nM
0.00015
BB-16
Bos taurus
-
peptidomimetric hydroxamate, synthetic inhibitor originally targeted for matrix metalloproteinases, IC50: 150 nM
0.00017
C-terminal 40-kDa fibronectin fragment
Bos taurus
-
wild type enzyme IC50: 170 nM, complete inhibition at 750 nM
-
0.00001
DPC
Bos taurus
-
non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 10 nM
0.00011
fibronectin
0.000079 - 0.00021
marimastat
0.1
N-(biphenyl-3-ylsulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.1 mM
0.003
N-(biphenyl-4-ylsulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.003 mM
0.1
N-(biphenyl-4-ylsulfonyl)-L-valine
Rattus norvegicus
-
IC50: 0.1 mM
0.012
N-(biphenyl-4-ylsulfonyl)-N-(pyridin-3-ylmethyl)-D-valine
Rattus norvegicus
-
IC50: 0.012 mM
0.0016
N-(biphenyl-4-ylsulfonyl)-N-methyl-D-valine
Rattus norvegicus
-
IC50: 0.0016 mM
0.2
N-([3'-[(acetylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
IC50 above 0.2 mM, pH and temperature not specified in the publication
0.0075
N-([4'-[(1-benzofuran-2-ylcarbonyl)amino]biphenyl-4-yl]sulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.0075 mM
0.00035
N-([4'-[(1-benzofuran-2-ylcarbonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.00035 mM
0.015
N-([4'-[(2-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0024
N-([4'-[(2-methylpyridin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0005
N-([4'-[(2-methylquinolin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.00042
N-([4'-[(3-bromobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0004
N-([4'-[(3-chlorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0008
N-([4'-[(3-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0026
N-([4'-[(3-fluorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0037
N-([4'-[(3-hydroxybenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.00054
N-([4'-[(3-nitrobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0014
N-([4'-[(4-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.1
N-([4'-[(benzoylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
IC50 around 0.1 mM, pH and temperature not specified in the publication
0.025
N-([4'-[(benzylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
IC50 around 0.025 mM, pH and temperature not specified in the publication
0.0116
N-([4'-[(furan-2-yloxy)carbonyl]biphenyl-4-yl]sulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.0116 mM
0.0056
N-([4'-[(phenylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0082
N-([4'-[(phenylsulfonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0004
N-([4'-[(Z)-2-(1-benzofuran-2-yl)ethenyl]biphenyl-4-yl]sulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.0004 mM
0.0038
N-([4'-[2-(1-benzofuran-2-yl)-2-oxoethyl]biphenyl-4-yl]sulfonyl)-D-valine
Rattus norvegicus
-
IC50: 0.0038 mM
0.05
N-[(2'-aminobiphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.05 mM
0.02
N-[(2'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.02 mM
0.03
N-[(2-aminobiphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.03 mM
0.009
N-[(3'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.009 mM
0.0046
N-[(4'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.0046 mM
0.0132
N-[(4'-phenoxybiphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0027
N-[(4'-[1-[3-(trifluoromethyl)phenyl]ethoxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.000086
N-[(4'-[[(3-methyl-1-benzofuran-2-yl)carbonyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.000086 mM
0.0007
N-[(4'-[[(3-methyl-1-benzofuran-2-yl)oxy]methyl]biphenyl-4-yl)sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.0007 mM
0.0091
N-[(4'-[[2-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0022
N-[(4'-[[2-(trifluoromethyl)pyridin-4-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.00076
N-[(4'-[[3-(methoxycarbonyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.00031
N-[(4'-[[3-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0019
N-[(4'-[[4-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0047
N-[(4'-[[6-(trifluoromethyl)pyridin-2-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.2
N-[(4'-[[acetyl(methyl)amino]methyl]biphenyl-4-yl)sulfonyl]-D-valine
Homo sapiens
-
IC50 above 0.2 mM, pH and temperature not specified in the publication
0.000004
N-[[(4S)-4-(1-methylimidazol-2-yl)-2,5-dioxo-imidazolidin-4-yl]methyl]-5-(trifluoromethyl)benzofuran-2-carboxamide
Homo sapiens
-
pH 7.5, 22C
0.0014
N-[[4'-(1-benzofuran-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Rattus norvegicus
-
IC50: 0.0014 mM
0.0055
N-[[4'-(benzyloxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.075
N-[[4'-(cyclohexylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
IC50 above 0.075 mM, pH and temperature not specified in the publication
0.0014
N-[[4'-(naphthalen-1-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0008
N-[[4'-(naphthalen-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.033
N-[[4'-(pyridin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.03
N-[[4'-(pyridin-3-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
IC50 around 0.03 mM, pH and temperature not specified in the publication
0.0085
N-[[4'-(pyridin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.0106
N-[[4'-(quinolin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.001
N-[[4'-(quinolin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
Homo sapiens
-
pH and temperature not specified in the publication
0.00021
N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine
Homo sapiens
-
37C, pH and temperature not specified in the publication
0.005
pyrogallol
Sus scrofa
-
pH 7.5, 37C
0.000076
SE206
Bos taurus
-
macrocyclic derivate of BB-16, IC50: 76 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9.5
-
-
7.2
-
assay at
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 10
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 65
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
low expression in non-atherosclerotic aorta
Manually annotated by BRENDA team
-
from patients with stable effort angina pectoris, acute coronary syndromes and in controls. Higher levels of ADAMTS4 are found with progression of coronary artery disease from stable effort angina pectoris to unstable angina pectoris to non-ST-segment elevation acute myocardial infarction and to ST-segment elevation acute myocardial infarction
Manually annotated by BRENDA team
-
mRNA is present in heart tissue
Manually annotated by BRENDA team
ADAMTS-4 mRNA is relatively abundant in tubulogenic and control HUVEC cultures. Both mRNA and protein are significantly elevated in tubulogenic cultures versus controls
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
ADAMTS-4 is the highest expressed aggrecanase in normal larynx, while ADAMTS-5 is the main aggrecanase in laryngeal squamous cell carcinoma
Manually annotated by BRENDA team
-
mRNA is present in lung tissue
Manually annotated by BRENDA team
-
metastatic lymph node
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
ADAMTS-4 is present in f-actin- and cortactin-positive podosome-like puncta in single cells and mature tubes
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
-
SDS-PAGE, small amount of ADAMTS4 found in porcupine articular cartilage without interleukin-1alpha treatment
42000
-
SDS-PAGE, active enzyme
46000
-
SDS-PAGE, primary form of ADAMTS4 in the interleukine-1alpha-treated porcupine articular cartilage
50000
-
SDS-PAGE, after incubation with alpha1-antitrypsin suggesting that there ADAMTS-4 has almost no proteolytic activity
53000
-
SDS-PAGE, activated ADAMTS-4
68000
-
p68 form of ADAMTS-4 cleaving recombinant bovine aggrecan preferentially within the CS-2 domain
73000
-
SDS-PAGE
98000
-
SDS-PAGE, proform of ADAMTS-4
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulations and multiway explorative data analysis on ADAMTS4 complexed with Marimastat and two cis-1(S)2(R)-amino-2-indanol ligands, and comparison with proteases MMP13, ADAMTS5. Determinant characteristics for ligand binding and selectivity among the three enzymes are to be found in the different protein conformation flexibility
-
vapour diffusion method with 10% PEG 4K, 0.1 M MES (pH 6.0)
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion exchange chromatography and cation exchange chromatography
-
anion-exchange chromatography
-
anti-FLAG affinity chromatography and S-200 Sephacryl gel filtration
-
anti-FLAG M2-agarose column chromatography
-
heparin-Sepharose chromatography
-
Macro S strong cation exchange and gelatin-agarose affinity column chromatography
-
Macro S, gelatin-agarose, affinity purification with bovine tissue inhibitor of metalloproteinases and an aggrecanase-inhibitor resin
-
Ni-NTA column chromatography, Radial Q column chromatography, and heparin-Sepharose column chromatography
-
polypropyl aspartamide hydrophobic interaction column chromatography, gel filtration, anti-Flag M2 affinity chromatogaphy, and Mono Q column chromatography
-
Q Sepharose, Zn-chelating, ether Toyopearl, Mono S
-
recombinant ADAMTS-1; recombinant ADAMTS-4
-
recombinant ADAMTS-4
-
SP-Sepharose fast flow column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; expression of ADAMTS-5 in Drosophila S2 cells
-
ADAMTS-1
-
ADAMTS-4 and ADAMTS-5
-
expressed in 293-EBNA cells
expressed in Chinese hamster ovary/A2 cell line
-
expressed in CHO cells
-
expressed in Drosophila SF9 cells
-
expressed in HEK293-EBNA cells
-
expressed in Saccharomyces cerevisiae and COS-7 cells
-
expressed in Saccharomyces cerevisiae strain AH109 and in Escherichia coli strain DH5alpha
-
expressed in Sf9 cells
expression in neurons from cerebral cortex from rats
-
expression of ADAMTS-4 in CHO/A2 cells
-
expression of ADAMTS-4 in human chondrosarcoma JJ012 cells
-
expression of cDNA in COS-7 cells
-
expression of cDNA in Drosophila S2 cells
-
expression of full length aggrecanase-1 and a C-terminal truncated form lacking the disintegrin and TSP motif in Drosophila S2 cells
-
recombinantly expressed
-
the full-length mature form of ADAMTS-4 with a C-terminally His-tagged sequence is expressed in an Epstein-Barr virus nuclear antigen-expressing human embryonic kidney 293 cell line, two C-terminal domain deletion enzymes containing both catalytic and disintegrin domains and the catalytic domain alone are expressed in Drosophila S2 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
disruption of chondrocyte hyaluran receptor CD44-hyaluran interactions with hyaluran oligosaccharides induces the transcription of endopeptidases ADAMTS-4 and ADAMTS-5 in a time- and dose-dependent manner
-
interleukin-1 and TNF-alpha upregulate ADAMTS-4 mRNA expression
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
the catalytic domain alone is enzymatically inactive
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
degradation
medicine
additional information
-
neurite extension mediated by the MAP kinase pathway, increased number of primary and secondary neurites