Information on EC 3.4.24.82 - ADAMTS-4 endopeptidase

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
3.4.24.82
-
RECOMMENDED NAME
GeneOntology No.
ADAMTS-4 endopeptidase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
a disintegrin and metalloprotease with thrombospondin motifs-4
O75173
-
a disintegrin and metalloproteinase with thrombospondin motif
-
-
a disintegrin and metalloproteinase with thrombospondin motifs-4
-
-
a disintegrin and metalloproteinase with thrombospondin motifs-4
-
-
a disintegrin and metalloproteinase with thrombospondin motifs-4
-
-
a disintegrin and metalloproteinase with thrombospondin-1-like motifs
-
-
ADAMTS 4
Mus musculus C3H/HEN
-
-
-
ADAMTS-1
-
-
ADAMTS-4
-
-
ADAMTS-4
-
ADAMTS-4 which lacks the C-terminal spacer domain
ADAMTS-4
O75173
-
ADAMTS-4
-
-
ADAMTS-4
Q8BNJ2
-
ADAMTS-4
-
-
ADAMTS-4
Q9ESP7
-
ADAMTS-4
-
-
ADAMTS-4 [a disintegrin and metalloproteinase with thrombospondin motifs-4]
-
-
ADAMTS-4 [a disintegrin and metalloproteinase with thrombospondin motifs-4]
O75173
-
ADAMTS-4-2
-
ADAMTS-4 lacking the spacer sequence
ADAMTS4
-
-
ADAMTS4
-
a disintegrin and metalloproteinase with thrombospondin motifs
ADAMTS4
-
a disintegrin and metalloproteinase with thrombospondinlike motif 4
ADAMTS4
O75173
-
ADAMTS4
-
-
agg-1
-
-
agg-1
Q8BNJ2
-
aggrecanase
-
-
aggrecanase 1
-
-
aggrecanase 1
-
-
aggrecanase 1
Mus musculus C3H/HEN
-
-
-
aggrecanase 1
-
-
aggrecanase-1
-
-
-
-
aggrecanase-1
-
-
aggrecanase-1
Q8BNJ2
-
aggrecanase-1
-
-
aggrecanase-1
Q9ESP7
-
aggrecanase-1
-
-
disintegrin and metalloproteinase with thrombospondin motif 4
-
-
TS-4
-
-
CAS REGISTRY NUMBER
COMMENTARY
147172-61-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
aggrecanase-1 and 2, i.e. ADAMTS-4 and 5
-
-
Manually annotated by BRENDA team
; recombinant
-
-
Manually annotated by BRENDA team
ADAMTS stands for: a disintegrin and metalloproteinase with thrombospondin motifs
-
-
Manually annotated by BRENDA team
ADAMTS stands for: a disintegrin and metalloproteinase with thrombospondin motifs; aggrecanase-2, i.e. ADAMTS-5
-
-
Manually annotated by BRENDA team
ADAMTS-1 also cleaves versican and aggrecane
-
-
Manually annotated by BRENDA team
aggrecanase-1 i.e. ADAMTS-4
GenBank
Manually annotated by BRENDA team
aggrecanase-2, i.e. ADAMTS-5
-
-
Manually annotated by BRENDA team
recombinantly expressed in Escherichia coli
-
-
Manually annotated by BRENDA team
no enzyme activity in TS-4 deficient mice
-
-
Manually annotated by BRENDA team
strain C3H/HEN
-
-
Manually annotated by BRENDA team
Mus musculus C3H/HEN
strain C3H/HEN
-
-
Manually annotated by BRENDA team
aggrecanase-1
SwissProt
Manually annotated by BRENDA team
aggrecanase-2
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
both long and short forms of the procollagen C-proteinase enhancers netrin-like (PCPE-1 NTR) domain show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1, and different ADAMTS-2, ADAMTS-4 or ADAMTS-5
physiological function
-
ADAMTS-4 inhibits human dermal microvascular endothelial cells (HuDMEC) vascular endothelial growth factor-stimulated vascular endothelial growth factor receptor R2 phosphorylation in a dose-related manner to give a maximum of about 65% inhibition at and above 30 nM. ADAMTS-4 reduces HuDMEC differentiation and migration
physiological function
-
ADAMTS-4 is responsible for aggrecan degradation during human articular cartilage destruction in vivo
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
?
show the reaction diagram
-
100 microg/ml
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
2-8 microg, assay at pH 7.2, 37C, reaction stopped by addition of 21 mM EDTA
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
2mg/ml, assay at 37C, 16 h
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
40 microg
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
ADAMTS-4 and ADAMTS-5 are the proteases responsible for the endogenous aggrecanase activity observed in IL-1beta stimulated bovine cartilage, cleavage at the Glu373-Ala374 site of aggrecan is measured
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
non-conservative mutation at P2' position of the bovine aggrecan (R375L) does not result in an observable difference in ADAMTS-4 susceptibility. Mutations in recombinant bovine aggrecan at Ser377 to Thr or Asn do not result in any significant difference in ADAMTS-4 cleavage. The S377Q mutation results in a significant reduction of cleavage by ADAMTS-4. The S377Q mutant is susceptible to cleavage by the C-terminally truncated ADAMTS-4. The S377A mutant is cleaved similarly to wild-type aggrecan
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
Glu373-Ala374 is the major cleavage site, aggrecanase also cleaves at Glu1971-Leu1972, which is located in the gap region in the chondroitin sulfate attachment region, aggrecanase does not cleave at the matrix metalloproteinase site Asn341-Phe342
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
preferred cleavage sites of aggrecanase-1 in descending order: E1667-G1668, E1771-A1772, E1871-L1872, E1480-G1481 and E373-A374
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
O75173
aggrecanase-1 does not cleave type II collagen, Tsp, fibronectin, casein or gelatin
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
ADAMTS-5, i.e. aggrecanase-2 cleaves at Glu373-Ala374
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-, O75173
ADAMTS-5, i.e. aggrecanase-2 cleaves at Glu373-Ala374
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-, O75173
ADAMTS-4 cleaves primarly at the Glu373-Ala374, but also, slowly and secondarily, at the Asn341-Phe342 site
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
the thrombospondin type-1 motif located within the C-terminus of aggrecanase-1 is critical for substrate binding and cleavage
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
both ADAMTS-1 and ADAMTS-4 cleave aggrecan at the Glu441-Ala442 bond
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
cleavage at the Glu373-Ala374 site
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
cleaves the Glu373-Ala374 bond
-
-
ir
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
aggrecanase-1 is responsible for the cleavage of aggrecan interglobular domain at the Glu373-Ala374 peptide bond
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
Mus musculus C3H/HEN
-
-
-
-
?
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
-
an aggrecan peptide with the N-terminal sequence ARGSVIL is released and quantified
-
-
?
aggrecan-interglobular domain + H2O
?
show the reaction diagram
-
cleavage site Glu373-Ala374 in aggrecaninterglobular domain
-
-
?
biglycan + H2O
?
show the reaction diagram
-
-
-
-
?
brevican + H2O
fragments of brevican
show the reaction diagram
-
-
-
-
?
brevican + H2O
fragments of brevican
show the reaction diagram
-
recombinantrat brevican, recombinant aggrecanase-1 most probably cleaves at Glu395-Ser396
-
?
brevican + H2O
?
show the reaction diagram
-
-
-
-
?
brevican + H2O
?
show the reaction diagram
-
-
-
-
?
brevican + H2O
?
show the reaction diagram
-
assay at 37C, 3 h, 25 nM recombinant ADAMTS
-
-
?
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
-
-
-
-
?
carboxymethylated transferrin + H2O
?
show the reaction diagram
-
little activity
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
fibromodulin + H2O
?
show the reaction diagram
-
-
-
-
?
fibromodulin + H2O
?
show the reaction diagram
-
cleaves at the Tyr44-Ala45 bond
-
-
?
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
-
-
-
-
?
N-procollagen + H2O
?
show the reaction diagram
-
-
-
-
?
QTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLK + H2O
QTVTWPDMELPLPRNITEGE + ARGSVILTVKPIFEVSPSPLK
show the reaction diagram
-
-
-
?
recombinant Agg1 + H2O
fragments of recombinant Agg1
show the reaction diagram
-
-
-
-
?
recombinant Agg1 + H2O
fragments of recombinant Agg1
show the reaction diagram
-
rAGG1 is composed of the complete interglobular domain, i.e. IGD, of human aggrecan, flanked by the marker sequences FLAG at the amino terminus and human immunglobulin G1 constant region at the C-terminus
-
?
transferrin + 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 + H2O
?
show the reaction diagram
-
-
-
-
?
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
-
-
-
-
?
[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
-
-
-
-
?
matrilin-3 + H2O
?
show the reaction diagram
-
cleaves at Glu435/Ala436 generating two species of 45 and 5 kDa
-
-
?
additional information
?
-
-
a disintegrin and metalloproteinase with thrombospondin motifs-4, aggrecanase 1
-
-
-
additional information
?
-
-
recombinant protein substrate based on the IGD (interglobular domain) of aggrecan, gst-IGD-flag
-
-
-
additional information
?
-
-
ADAMTS-4 binds to vascular endothelial growth factor
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
aggrecan + H2O
?
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
ADAMTS-4 and ADAMTS-5 are the proteases responsible for the endogenous aggrecanase activity observed in IL-1beta stimulated bovine cartilage
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
-
-
-
-
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
cleavage at the Glu373-Ala374 site
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
aggrecanase-1 is responsible for the cleavage of aggrecan interglobular domain at the Glu373-Ala374 peptide bond
-
-
?
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 ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
Ca2+-dependent metalloproteinase
Zn2+
-
contains a zinc catalytic domain
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
(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
Q8BNJ2
-
(R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
(R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
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
-
0.00066 mM, 50% inhibition, hydroxamate-based matrix metalloproteinase inhibitor
AG3340
-
non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 120 nM
AG490
-
0.01 mM
alpha2-Macroglobulin
-
-
-
batimastat
-
-
BB-16
-
0.000548 mM, 50% inhibition
BB-16
-
0.000159 mM, 50% inhibition
BB-16
-
0.1 mM, complete inhibition of aggrecanase 1 and 2
BB-16
-
peptidomimetric hydroxamate, synthetic inhibitor originally targeted for matrix metalloproteinases, IC50: 150 nM
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
EDTA
-
5 mM, complete inhibition
EDTA
-
1 mM, complete inhibition of aggrecanase 1 and 2
EGTA
-
5 mM, complete inhibition
enoxaparin
-
-
Fibronectin
-
IC50: 110 nM
-
Fibronectin
-
wild type enzyme IC50: 110 nM, complete inhibition at 500 nM
-
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
-
0.1 mg/ml, selective inhibition of full-length ADAMTS-4
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
-
Keratan sulfate
-
-
LY294002
-
0.01 mM, reduces ADAMTS-4 expression
marimastat
-
IC50: 210 nM
marimastat
-
-
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-[[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
-
demonstrates noncompetitive inhibition kinetics
SE206
-
0.000137 mM, 50% inhibition
SE206
-
0.000076 mM, 50% inhibition
SE206
-
0.1 mM, complete inhibition of aggrecanase 1 and 2
SE206
-
macrocyclic derivate of BB-16, IC50: 76 nM
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
-
20 nM, complete inhibition
-
tissue inhibitor of metalloproteinases-3
-
TIMP-3
-
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
-
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
minocycline
-
dose-dependently inhibits the activity of rhADAMTS4 in vitro
additional information
-
no inhibitory effect of alpha1-antitrypsin
-
additional information
-
ADAMTS-4 is not inhibited by 125 nM or less tissue inhibitor of metalloproteinase-1
-
additional information
-
no inhibition by tissue inhibitor of metalloproteinases 1 or tissue inhibitor of metalloproteinases 2 at 100 nM
-
additional information
-
no inhibition of ADAMTS4 deletion mutants including DELTASp (DELTAArg693-Lys837, lacking the spacer domain)
-
additional information
-
substrate specifity of ADAMTS-4 against recombinant aggrecan, aggrecan mutants V356A-V361A-E362D, V361Q-E362K, D360H-V361Q-E362K, S377Q lead to aggrecan cleavage inhibition
-
additional information
-
lower expression level in majority of primary tumors
-
additional information
-
down-regulation of IL-1beta-induced ADAMTS-4 activation by Ras knockdown or inhibition of reactive oxygen species by antioxidants along with ablation of MyD88, IRAK1, or TRAF6; inducing effect of IL-1beta partially blocked by knockdown of adaptor proteins MyD88, IRAK1 or TRAF6
-
additional information
-
design of ADAMTS-4 inhibitors. No inhibition observed with the ADAMTS-5 inhibitors: 2-[4-(benzyloxy)phenyl]-3-oxoisoindoline-4-carboxylic acid or 2-[4-(benzyloxy)phenyl]-N-hydroxy-3-oxoisoindoline-4-carboxamide
-
additional information
-
design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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-1alpha
-
induced gene expression in osteoarthritic chondrocytes
-
interleukin-1alpha
-
increase of ADAMTS-4 in wild-type mice
-
interleukin-1alpha
-
-
-
NaCl
-
the optimum NaCl concentration for aggrecan degradation is between 12.5 and 50 mM
oncostatin M
-
dose-depedent stimulation of expression, 1-100 ng/ml
-
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
-
-
-
Interleukin-1beta
-
10 ng/ml
-
additional information
-
57fold enhanced expression during infection with Borrelia burgdorferi
-
additional information
-
enhanced expression during late-stage infections with Borrelia burgdorferi
-
additional information
-
4.2fold enhanced expression during infection with Borrelia burgdorferi
-
additional information
-
expression is not stimulated by interleukin-1beta
-
additional information
-
not stimulated by phorbol ester
-
additional information
-
higher enzyme expression in degenerated intervertebral discs
-
additional information
-
substrate specifity of ADAMTS-4 against recombinant aggrecan, aggrecan mutants T370Q and T352V-T355V-T357V lead to a faster aggrecan cleavage
-
additional information
-
increased gene expression is result of DNA methylation, resulting in heritable and permanent expression of ADAMTS-4 in osteoarthritis chondrocytes; increasing osteoarthritis severity results in increased number of ADAMTS-4 producing chondrocytes and in increased depth at which these chondrocytes are found, in healty cartilage ADAMTS-4 producing chondrocytes only in little numbers and located near the surface
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0203
-
Aggrecan
-
in 100 mM NaCl
-
0.279
-
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
-
ADAMTS-4-2, at 25C
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
-
ADAMTS-4-2, at 25C
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
-
[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
-
ADAMTS-4-2, at 25C
-
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
-
ADAMTS-4-2, at 25C
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.49
-
Aggrecan
-
in 100 mM NaCl
-
0.072
-
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
-
ADAMTS-4-2, at 25C
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
-
ADAMTS-4-2, at 25C
1.16
-
chondroitin 4-sulfate
-
in 100 mM NaCl
0.012
-
[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
-
ADAMTS-4-2, at 25C
-
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
-
ADAMTS-4-2, at 25C
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00268
-
(E)-4-[2-(3,5-dihydroxyphenyl)ethenyl]1,2-benzenediol
-
pH 7.5, 37C, substrate: C6-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-Gly-Thr-Lys(7-methoxycoumarin-4-yl)-Gly-GluLeuGluGly-ArgGly-Thr-Lys(Dnp)-Gly-Ile-Ser-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-NH2
0.00506
-
(E)-4-[2-(3,5-dihydroxyphenyl)ethenyl]1,2-benzenediol
-
pH 7.5, 37C, substrate: pH 7.5, 37C, substrate: Lys(7-methoxycoumarin-4-yl)-Lys-Gln-Glu-Phe-Arg-Gly-Gln-Thr-Lys(Dnp)-NH2
0.0453
-
doxycycline
-
rhADAMTS4(F213-R695), pH and temperature not specified in the publication
0.0611
-
doxycycline
-
rhADAMTS4(F213-A579), pH and temperature not specified in the publication
8e-05
-
enoxaparin
-
-
0.000105
-
GGWGPWGPWGDCSRTCGGG
-
-
-
0.0869
-
minocycline
-
rhADAMTS4(F213-R695), pH and temperature not specified in the publication
0.0001
-
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-3
-
0.00013
-
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-1
-
0.00018
-
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-2
-
0.00064
-
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-4
-
0.00634
-
pyrogallol
-
pH 7.5, 37C, substrate: C6-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-Gly-Thr-Lys(7-methoxycoumarin-4-yl)-Gly-GluLeuGluGly-ArgGly-Thr-Lys(Dnp)-Gly-Ile-Ser-(Gly-Pro-Hyp-Pro-Hyp-Gly)2-Gly-Pro-Hyp-NH2
0.041
-
pyrogallol
-
pH 7.5, 37C, substrate: Lys(7-methoxycoumarin-4-yl)-Lys-Gln-Glu-Phe-Arg-Gly-Gln-Thr-Lys(Dnp)-NH2
0.026
-
QEYKAHHSYKLMS
-
at 37C
2.28e-05
-
SC81956
-
at 37C
0.12
-
tetracycline
-
rhADAMTS4(F213-A579), pH and temperature not specified in the publication
0.761
-
tetracycline
-
rhADAMTS4(F213-R695), pH and temperature not specified in the publication
7.9e-06
-
TIMP-3
-
-
-
2e-05
-
tinzaparin
-
-
-
3.3e-06
-
tissue inhibitor of matrix metalloproteinases-3
-
-
-
0.00022
-
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-1; pH 7.5, 37C, isoenzyme ADAMTS4-2
-
0.0004
-
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-3
-
0.00051
-
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37C, isoenzyme ADAMTS4-4
-
0.0973
-
minocycline
-
rhADAMTS4(F213-A579), pH and temperature not specified in the publication
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]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0028
-
(2R)-2-(biphenyl-4-ylsulfonyl)-3-(1H-indol-2-yl)propanoic acid
-
IC50: 0.0028 mM
0.0043
-
(2R)-2-(biphenyl-4-ylsulfonyl)-3-phenylpropanoic acid
-
IC50: 0.0043 mM
0.0011
-
(2R)-2-(biphenyl-4-ylsulfonyl)pentanedioic acid
-
IC50: 0.0011 mM
0.0055
-
(2R)-2-(biphenyl-4-ylsulfonyl)propanoic acid
-
IC50: 0.0055 mM
0.02
-
(2R)-2-([[3'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
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
-
pH and temperature not specified in the publication
0.0021
-
(2R)-2-([[3'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.1
-
(2R)-2-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
IC50 around 0.1 mM, pH and temperature not specified in the publication
0.00042
-
(2R)-2-([[4'-(carbamoyloxy)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.0041
-
(2R)-2-([[4'-(carbamoyloxy)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.015
-
(2R)-2-([[4'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.003
-
(2R)-2-[(biphenyl-4-ylsulfonyl)amino]-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.0084
-
(2R)-2-[[(3'-carbamoylbiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.04
-
(2R)-2-[[(3'-cyanobiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.009
-
(2R)-2-[[(3'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.0046
-
(2R)-2-[[(4'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid
-
pH and temperature not specified in the publication
0.05
-
(2R)-3-methyl-2-[([4'-[(methylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)amino]butanoic acid
-
IC50 around 0.05 mM, pH and temperature not specified in the publication
-
6.5e-05
-
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
-
pH 7.5, 37C
1.1e-06
-
(2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide
-
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
-
IC50: 145 nM
2.1e-06
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 2.1 nM
1.6e-05
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 16 nM
5e-07
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-chloro-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 0.5 nM
6.7e-05
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-ethylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 67 nM
3.9e-06
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-3-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 3.9 nM
2.7e-06
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 2.7 nM
4e-05
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-5-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 40 nM
3.8e-05
-
(2R,5R)-N,5-dihydroxy-1-([4-[(2-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 38 nM
0.0001
-
(2R,5R)-N,5-dihydroxy-1-([4-[(3-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 100 nM
0.0001
-
(2R,5R)-N,5-dihydroxy-1-([4-[(4-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide
-
IC50: 100 nM
1.8e-05
-
(2R,5R)-N,5-dihydroxy-1-[[4-(2-chloropyridin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 18 nM
9.1e-05
-
(2R,5R)-N,5-dihydroxy-1-[[4-(2-methylpyridin-3-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 91 nM
0.0001
-
(2R,5R)-N,5-dihydroxy-1-[[4-(isoquinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 100 nM
1.5e-05
-
(2R,5R)-N,5-dihydroxy-1-[[4-(quinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide
-
IC50: 15 nM
3e-06
-
(3R)-N2-(cyclopropylmethyl)-N1-hydroxy-3-(3-hydroxybenzyl)-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-L-aspartamide
-
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
Q8BNJ2
-
0.0002
-
(R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0049
-
(R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.001
-
(R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.00023
-
(R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0012
-
(R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0011
-
(R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0018
-
(R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
8e-05
-
(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
9e-05
-
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.00059
-
(R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.00043
-
(R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0017
-
(R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0001
-
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0016
-
(R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Q8BNJ2
-
0.0002
-
(R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.00073
-
(R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0052
-
(R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.006
-
(R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0009
-
(R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0019
-
(R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0004
-
(R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0008
-
(R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.02
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0032
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.00023
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.0004
-
(R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Q8BNJ2
-
0.015
-
2-[4-(benzyloxy)phenyl]-2,3-dihydro-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxylate
-
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
-
37C, pH and temperature not specified in the publication
0.1
-
3-[(biphenyl-4-ylsulfonyl)amino]-4-methylpentanoic acid
-
IC50: 0.1 mM
0.022
-
3-[[(4'-[[(1R)-1-carboxy-2-methylpropyl]sulfamoyl]biphenyl-4-yl)oxy]methyl]benzoic acid
-
IC50 around 0.022 mM, pH and temperature not specified in the publication
0.00012
-
AG3340
-
non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 120 nM
0.00015
-
BB-16
-
peptidomimetric hydroxamate, synthetic inhibitor originally targeted for matrix metalloproteinases, IC50: 150 nM
0.00017
-
C-terminal 40-kDa fibronectin fragment
-
wild type enzyme IC50: 170 nM, complete inhibition at 750 nM
-
1e-05
-
DPC
-
non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 10 nM
0.00011
-
Fibronectin
-
IC50: 110 nM
-
0.00011
-
Fibronectin
-
wild type enzyme IC50: 110 nM, complete inhibition at 500 nM
-
7.9e-05
-
marimastat
-
pH 7.5, 37C
0.00021
-
marimastat
-
IC50: 210 nM
0.1
-
N-(biphenyl-3-ylsulfonyl)-D-valine
-
IC50: 0.1 mM
0.003
-
N-(biphenyl-4-ylsulfonyl)-D-valine
-
IC50: 0.003 mM
0.1
-
N-(biphenyl-4-ylsulfonyl)-L-valine
-
IC50: 0.1 mM
0.012
-
N-(biphenyl-4-ylsulfonyl)-N-(pyridin-3-ylmethyl)-D-valine
-
IC50: 0.012 mM
0.0016
-
N-(biphenyl-4-ylsulfonyl)-N-methyl-D-valine
-
IC50: 0.0016 mM
0.2
-
N-([3'-[(acetylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine
-
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
-
IC50: 0.0075 mM
0.00035
-
N-([4'-[(1-benzofuran-2-ylcarbonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.00035 mM
0.015
-
N-([4'-[(2-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0024
-
N-([4'-[(2-methylpyridin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0005
-
N-([4'-[(2-methylquinolin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.00042
-
N-([4'-[(3-bromobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0004
-
N-([4'-[(3-chlorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0008
-
N-([4'-[(3-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0026
-
N-([4'-[(3-fluorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0037
-
N-([4'-[(3-hydroxybenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.00054
-
N-([4'-[(3-nitrobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0014
-
N-([4'-[(4-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.1
-
N-([4'-[(benzoylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine
-
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
-
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
-
IC50: 0.0116 mM
0.0056
-
N-([4'-[(phenylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
pH and temperature not specified in the publication
0.0082
-
N-([4'-[(phenylsulfonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine
-
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
-
IC50: 0.0004 mM
0.0038
-
N-([4'-[2-(1-benzofuran-2-yl)-2-oxoethyl]biphenyl-4-yl]sulfonyl)-D-valine
-
IC50: 0.0038 mM
0.05
-
N-[(2'-aminobiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.05 mM
0.02
-
N-[(2'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.02 mM
0.03
-
N-[(2-aminobiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.03 mM
0.009
-
N-[(3'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.009 mM
0.0046
-
N-[(4'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.0046 mM
0.0132
-
N-[(4'-phenoxybiphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.0027
-
N-[(4'-[1-[3-(trifluoromethyl)phenyl]ethoxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
8.6e-05
-
N-[(4'-[[(3-methyl-1-benzofuran-2-yl)carbonyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.000086 mM
0.0007
-
N-[(4'-[[(3-methyl-1-benzofuran-2-yl)oxy]methyl]biphenyl-4-yl)sulfonyl]-D-valine
-
IC50: 0.0007 mM
0.0091
-
N-[(4'-[[2-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.0022
-
N-[(4'-[[2-(trifluoromethyl)pyridin-4-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.00076
-
N-[(4'-[[3-(methoxycarbonyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.00031
-
N-[(4'-[[3-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.0019
-
N-[(4'-[[4-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.0047
-
N-[(4'-[[6-(trifluoromethyl)pyridin-2-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.2
-
N-[(4'-[[acetyl(methyl)amino]methyl]biphenyl-4-yl)sulfonyl]-D-valine
-
IC50 above 0.2 mM, pH and temperature not specified in the publication
0.0014
-
N-[[4'-(1-benzofuran-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
IC50: 0.0014 mM
0.0055
-
N-[[4'-(benzyloxy)biphenyl-4-yl]sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.075
-
N-[[4'-(cyclohexylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
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
-
pH and temperature not specified in the publication
0.0008
-
N-[[4'-(naphthalen-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.033
-
N-[[4'-(pyridin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.03
-
N-[[4'-(pyridin-3-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
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
-
pH and temperature not specified in the publication
0.0106
-
N-[[4'-(quinolin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.001
-
N-[[4'-(quinolin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine
-
pH and temperature not specified in the publication
0.00021
-
N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine
-
37C, pH and temperature not specified in the publication
0.005
-
pyrogallol
-
pH 7.5, 37C
7.6e-05
-
SE206
-
macrocyclic derivate of BB-16, IC50: 76 nM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
5300.0 mg/h/mg protein
additional information
-
-
39.8 units/nmol protein, one unit of enzyme activity represents the release of 0.001 mg of glycosaminoglycan/min at 37C at pH 7.5, wild type enzyme
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.2
-
-
assay at
7.5
-
-
assay at
8
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
10
-
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
65
-
-
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
low expression in non-atherosclerotic aorta
Manually annotated by BRENDA team
-
explant culture, stimulation with retinoic acid, interleukin-1 or tumour necrosis factor induces aggrecanase activity
Manually annotated by BRENDA team
-
healthy humans or humans with osteoarthritis
Manually annotated by BRENDA team
-
cell culture, expression of aggrecanase-1 mRNA is induced if cells are treated with beta-amyloid
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 brain tissue
Manually annotated by BRENDA team
-
cartilage culture
Manually annotated by BRENDA team
-
articular chondrocyte
Manually annotated by BRENDA team
-
humans with osteoarthritis
Manually annotated by BRENDA team
-
degradative chondrocytes express ADAMTS-4
Manually annotated by BRENDA team
-
femoral head
Manually annotated by BRENDA team
-
mRNA is present in heart tissue
Manually annotated by BRENDA team
Mus musculus C3H/HEN
-
-
-
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 ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
36000
-
-
SDS-PAGE, small amount of ADAMTS4 found in porcupine articular cartilage without interleukin-1alpha treatment
40000
-
-
SDS-PAGE, activated ADAMTS-4
40000
-
-
p40 form of ADAMTS-4 cleaving recombinant bovine aggrecan preferentially within the interglobular domain
40000
-
-
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
64000
-
-
SDS-PAGE, active form of ADAMTS-4
64000
-
-
SDS-PAGE
68000
-
-
p68 form of ADAMTS-4 cleaving recombinant bovine aggrecan preferentially within the CS-2 domain
70000
-
-
SDS-PAGE, full-length enzyme
70000
-
-
active enzyme, SDS-PAGE
73000
-
-
SDS-PAGE
75000
-
-
SDS-PAGE, inactive full-length enzyme
75000
-
-
SDS-PAGE, glycosylated active enzyme form
98000
-
-
SDS-PAGE, proform of ADAMTS-4
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 62000, SDS-PAGE
?
-
x * 69000, recombinant aggrecanase-1, SDS-PAGE
?
-
x * 68000, following incubation at 37C for 16 h, ADAMTS-4 is detected as isoforms of 68000 Da, 53000 Da and 40000 Da
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
autocatalytic cleavage, cleavage sites are Lys694-Phe695 and Thr581-Phe582, following incubation at 37C for 16 h, ADAMTS-4 is detected as isoforms of 68000 Da, 53000 Da and 40000 Da
proteolytic modification
-
in vivo production of proteolytically active ADAMTS-4 requires removal of the prodomain by a furin-like activity and MMP-mediated removal of a portion of the C-terminal spacer domain
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
vapour diffusion method with 10% PEG 4K, 0.1 M MES (pH 6.0)
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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
-
Q Sepharose, Zn-chelating, ether Toyopearl, Mono S
-
SP-Sepharose fast flow column chromatography
-
anion exchange chromatography and cation exchange chromatography
-
anion-exchange chromatography
-
anti-FLAG M2-agarose column chromatography
-
heparin-Sepharose chromatography
-
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
-
recombinant ADAMTS-1; recombinant ADAMTS-4
-
recombinant ADAMTS-4
-
anti-FLAG affinity chromatography and S-200 Sephacryl gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ADAMTS-4 and ADAMTS-5
-
expressed in Drosophila SF9 cells
-
expressed in Saccharomyces cerevisiae strain AH109 and in Escherichia coli strain DH5alpha
-
-
-, O75173
; expression of ADAMTS-5 in Drosophila S2 cells
-
ADAMTS-1
-
expressed in 293-EBNA cells
-
expressed in Chinese hamster ovary/A2 cell line
-
expressed in CHO cells
-
expressed in HEK293-EBNA cells
-
expressed in Saccharomyces cerevisiae and COS-7 cells
-
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
-
expressed in Sf9 cells
-
PCR; PCR
Q9GLK6, Q9GLK7
expressed in 293-EBNA cells
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
interleukin-1 and TNF-alpha upregulate ADAMTS-4 mRNA expression
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E362Q
-
active site mutant, no aggrecanase activity, no autocatalytic cleavage
E362Q
-
inactive mutant, single point mutation (G to C) leading to the amino acid change at residue 362 located within the catalytic domain of ADAMTS4
E362A
-
inactive mutant enzyme with mutation of Glu to Ala at position 362
E362Q
-
proteolytically inactive, but still activationg effect on neurite extension
additional information
-
the catalytic domain alone is enzymatically inactive
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
degradation
-
degradation of cartilage in late-stage Lyme arthritis
degradation
-
degradation of cartilage proteoglycan (aggrecan) in osteoarthritis and rheumatoid arthritis
medicine
-
therapeutic target in osteoarthritis
degradation
-
degradation of cartilage in late-stage Lyme arthritis
degradation
-
abrasion of cartilage aggrecan in rheumatoid arthritis and osteoarthritis
medicine
-
therapeutic target in osteoarthritis
medicine
-
the pattern of ADAMTS4 release observed is clearly different in various forms of ACS. ADAMTS4 shows a weak correlation with high-sensitivity C-reactive protein. However, no significant correlation is found between ADAMTS4 and troponin T in acute coronary syndromes patients
medicine
-
design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5, which will be required for chronic osteoarthritis therapy
degradation
-
degradation of cartilage in late-stage Lyme arthritis
medicine
-
therapeutic target in osteoarthritis
medicine
Q8BNJ2
stop progression of cartilage degradation in osteoarthritis by prevention of aggrecan cleavage via inhibition of aggrecanase-1
degradation
Mus musculus C3H/HEN
-
degradation of cartilage in late-stage Lyme arthritis
-
medicine
-
therapeutic target in osteoarthritis
medicine
-
ADAMTS-4 is a key enzyme in osteoarthritis
additional information
-
neurite extension mediated by the MAP kinase pathway, increased number of primary and secondary neurites