Information on EC 3.4.24.82 - ADAMTS-4 endopeptidase and Organism(s) Homo sapiens

-

-

?

carboxyfluorescein-AELQGRPISIAK-N,N,N',N'-tetramethyl-6-carboxyrhodamine + H2O

carboxyfluorescein-AE + LQGRPISIAK-N,N,N',N'-tetramethyl-6-carboxyrhodamine

-

-

?

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

-

709790

-

?

carboxymethylated transferrin + H2O

?

cartilage disc extract supernantant + H2O

hyaluron + hyaladherins

-

-

?

cartilage oligomeric matrix protein + H2O

?

-

-

?

chondroitin 4-sulfate + H2O

?

-

-

?

decorin + H2O

?

-

680781, 720093

-

?

DVQEFRGVTAVIR + H2O

?

-

-

?

FAM-AELQGRPISIAK-TAMRA + H2O

?

-

activity measured using a quenched fluorescent substrate

707442

-

?

fibromodulin + H2O

?

Fibronectin + H2O

?

-

680781

-

?

fibulin-2 + H2O

?

-

754958

-

?

HNEFRQRETYMVF + H2O

?

-

-

?

matrilin-2 + H2O

?

-

734743

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

?

-

cleaves at Glu435/Ala436 generating two species of 45 and 5 kDa

-

?

porcine aggrecan + H2O

?

-

-

?

versican + H2O

?

-

670737

-

?

versican + H2O

fragments of versican

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

638960

-

638960

?

versican V1 + H2O

fragments of versican V1

-

-

?

versican V2 + H2O

glial hyaluronate binding protein + ?

-

667468

-

?

VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG + H2O

?

[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

?

-

-

?

additional information

?

-

3 entries

aggrecan + H2O

?

3 entries

aggrecan + H2O

fragments of aggrecan

brevican + H2O

fragments of brevican

-

-

?

carboxymethylated transferrin + H2O

?

-

-

?

cartilage oligomeric matrix protein + H2O

?

-

-

?

decorin + H2O

?

-

-

?

fibromodulin + H2O

?

-

-

?

versican V1 + H2O

fragments of versican V1

-

-

?

Zn2+

(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

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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

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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

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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

-

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-[[(4'-[[(1R)-1-carboxy-2-methylpropyl]sulfamoyl]biphenyl-4-yl)oxy]methyl]benzoic acid

-

acetyl-DVQEFRGVTAVIRNH2

-

acetyl-HNEFRQRETYMVF-NH2

-

AG490

-

0.01 mM

antibody 237-53

antibody 237-53 almost completely blocks the activity of the enzyme in a molar ratio of 1:5 (enzyme:antibody)

-

batimastat

-

BB-16

0.000159 mM, 50% inhibition

calcium pentosan polysulfate

-

no impact on gene expression, but directly inhibit the aggrecanase activity

697932

-

D-mannosamine

-

1.5 mM

doxycycline

-

dose-dependently inhibits the activity of rhADAMTS4 in vitro

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

heparin

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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

Janus kinase 2 inhibitor

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10 g/ml

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Janus kinase 3 inhibitor

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30 g/ml

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KB-R7785

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LY294002

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0.01 mM, reduces ADAMTS-4 expression

marimastat

minocycline

-

dose-dependently inhibits the activity of rhADAMTS4 in vitro

N-([3'-[(acetylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(2-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(2-methylpyridin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(2-methylquinolin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(3-bromobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(3-chlorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(3-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(3-fluorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(3-hydroxybenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(3-nitrobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(4-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(benzoylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(benzylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(phenylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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N-([4'-[(phenylsulfonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine

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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

709790

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N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3

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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

707445

-

N-[(4'-phenoxybiphenyl-4-yl)sulfonyl]-D-valine

-

N-[(4'-[1-[3-(trifluoromethyl)phenyl]ethoxy]biphenyl-4-yl)sulfonyl]-D-valine

-

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-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-5-(trifluoromethyl)-1-benzofuran-2-carboxamide

-

754392

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

734452

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

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N-[[4'-(quinolin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine

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N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine

-

NL-71-101

-

0.02 mM, reduces ADAMTS-4 expression

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

-

SC81956

-

SE206

0.000076 mM, 50% inhibition

tetracycline

-

dose-dependently inhibits the activity of rhADAMTS4 in vitro

TIMP-3

-

680792, 720093

-

TIMP3

-

-

Tissue inhibitor of metalloproteinase-1

-

150 nM or 270 nM

-

tissue inhibitor of metalloproteinases 3

-

668117

-

tissue inhibitor of metalloproteinases-3

-

Tripterygium wilfordii Hook F extract

-

667400

-

triptolide

-

600 nM, PG490

667400

U0126

inhibition of MAP kinase signaling pathway result in inhibition of neurite outgrowth induced by ADAMTS4

XS309

0.002185 mM, 50% inhibition

additional information

7 entries

-

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

699350

-

interferon gamma

-

677894

-

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

-

syndecan-1

-

proteoglycan form of syndecan-1

-

tissue necrosis factor alpha

-

677894

-

TNF-alpha

-

10 ng/ml

699350

-

transforming growth factor beta

-

-

Tumor necrosis factor alpha

-

-

tumour necrosis factor

-

668117

-

additional information

9 entries

-

0.015

5-carboxyfluorescein-Ala-Glu-Leu-Gln-Gly-Arg-Pro-Ile-Ser-Ile-Ala-Lys-N,N,N',N'-tetramethyl-6-carboxyrhodamine

at pH 7.5 and 37°C

754633

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

0.0471 - 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

-

1.49

Aggrecan

-

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

-

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

-

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

0.0453 - 0.0611

doxycycline

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

4 entries

-

0.12 - 0.761

tetracycline

0.0000079

TIMP-3

-

-

0.00022 - 0.00051

tissue inhibitor of metalloproteinases-3

4 entries

-

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

707445

-

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, 37°C

0.0000011

(2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide

Homo sapiens

-

37°C, 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

Homo sapiens

-

IC50: 100 nM

0.0001

(2R,5R)-N,5-dihydroxy-1-([4-[(4-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide

Homo sapiens

-

IC50: 100 nM

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, 37°C

0.015

2-[4-(benzyloxy)phenyl]-2,3-dihydro-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxylate

Homo sapiens

-

37°C, 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

-

37°C, pH and temperature not specified in the publication

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

0.0000789

antibody 237-53

Homo sapiens

at pH and 37°C

-

0.000079

marimastat

Homo sapiens

-

pH 7.5, 37°C

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

0.015

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

0.0056

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

0.0132

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

0.0091

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, 22°C

734452

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

-

37°C, pH and temperature not specified in the publication

7 - 9.5

-

7.2

-

assay at

696436

7.5

8

annulus fibrosus disci intervertebralis

-

assay at

37

-

-

low expression in non-atherosclerotic aorta

-

atherosclerotic carotid plaque

-

-

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

-

-

chondrosarcoma cell line

-

commercial preparation

coronary atherosclerotic plaque

-

734743

-

-

femoral head

-

-

-

-

head and neck squamous cell carcinoma cell line

-

primary tumor

mRNA is present in heart tissue

-

ADAMTS-4 mRNA is relatively abundant in tubulogenic and control HUVEC cultures. Both mRNA and protein are significantly elevated in tubulogenic cultures versus controls

-

-

-

ADAMTS-4 is the highest expressed aggrecanase in normal larynx, while ADAMTS-5 is the main aggrecanase in laryngeal squamous cell carcinoma

mRNA is present in lung tissue

lymph node

prostate cancer cell line

-

metastatic lymph node

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ADAMTS-4 is present in f-actin- and cortactin-positive podosome-like puncta in single cells and mature tubes

2102

734403

physiological function

5 entries

O75173 pBLAST

ATS4_HUMAN

837

1

90197

Swiss-Prot

Show Sequence

Secretory Pathway (Reliability: 2)

40000

42000

-

SDS-PAGE, active enzyme

50000

-

SDS-PAGE, after incubation with alpha1-antitrypsin suggesting that there ADAMTS-4 has almost no proteolytic activity

53000

-

SDS-PAGE, activated ADAMTS-4

667360

64000

-

SDS-PAGE

68000

69000

x * 69000, recombinant aggrecanase-1, SDS-PAGE

638956

70000

-

active enzyme, SDS-PAGE

680751, 680781

75000

?

4 entries

proteolytic modification

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)

-

682743

E362Q

3 entries

additional information

-

the catalytic domain alone is enzymatically inactive

-

anion exchange chromatography and cation exchange chromatography

-

anion-exchange chromatography

-

667468

anti-FLAG M2 affinity gel filtration

754633

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

Strep-Tactin Sepharose column chromatography

-

ADAMTS-1

expressed in 293-EBNA cells

-

expressed in Chinese hamster ovary/A2 cell line

-

expressed in CHO cells

-

682743

expressed in HEK-293T cells

expressed in HEK293-EBNA cells

-

expressed in Saccharomyces cerevisiae and COS-7 cells

-

expressed in Sf9 cells

-

680751, 709044

expression in neurons from cerebral cortex from rats

expression of ADAMTS-4 in CHO/A2 cells

638962

expression of ADAMTS-4 in human chondrosarcoma JJ012 cells

638964

expression of ADAMTS-5 in Drosophila S2 cells

638965

expression of cDNA in COS-7 cells

638956

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

-

707442

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

-

interleukin-1 and TNF-alpha upregulate ADAMTS-4 mRNA expression

-

degradation

medicine

additional information

neurite extension mediated by the MAP kinase pathway, increased number of primary and secondary neurites

638953

Little, C.B.; Flannery, C.R.; Hughes, C.E.; Mort, J.S.; Roughley, P.J.; Dent, C.; Caterson, B.

Aggrecanase versus matrix metalloproteinases in the catabolism of the interglobular domain of aggrecan in vitro

Biochem. J.

344

61-68

1999

Bos taurus, Homo sapiens, Sus scrofa

-

Tortorella, M.D.; Burn, T.C.; Pratta, M.A.; Abbaszade, I.; Hollis, J.M.; Liu, R.; Rosenfeld, S.A.; Copeland, R.A.; Decicco, C.P.; Wynn, R.; Rockwell, A.; Yang, F.; Duke, J.L.; Solomon, K.; George, H.; Bruckner, R.; Nagase, H.; Itoh, Y.; Ellis, D.M.; Ross, H.; Wiswall, B.H.; Murphy, K.; Hillman, M.C., Jr.; Hollis, G.F.; Arner, E.C.; et al.

Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins

Science

284

1664-1666

1999

Bos taurus, Homo sapiens (O75173)

10356395

638956

Nakamura, H.; Fujii, Y.; Inoki, I.; Sugimoto, K.; Tanzawa, K.; Matsuki, H.; Miura, R.; Yamaguchi, Y.; Okada, Y.

Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites

J. Biol. Chem.

275

38885-38890

2000

Homo sapiens (O75173)

10986281

638957

Tortorella, M.D.; Pratta, M.; Liu, R.Q.; Austin, J.; Ross, O.H.; Abbaszade, I.; Burn, T.; Arner, E.

Sites of aggrecan cleavage by recombinant human aggrecanase-1 (ADAMTS-4)

J. Biol. Chem.

275

18566-18573

2000

Bos taurus, Homo sapiens (O75173), Homo sapiens

10751421

Tortorella, M.; Pratta, M.; Liu, R.Q.; Abbaszade, I.; Ross, H.; Burn, T.; Arner, E.

The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage

J. Biol. Chem.

275

25791-25797

2000

Homo sapiens (O75173), Homo sapiens

10827174

638960

Sandy, J.D.; Westling, J.; Kenagy, R.D.; Iruela-Arispe, M.L.; Verscharen, C.; Rodriguez-Mazaneque, J.C.; Zimmermann, D.R.; Lemire, J.M.; Fischer, J.W.; Wight, T.N.; Clowes, A.W.

Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4

J. Biol. Chem.

276

13372-13378

2001

Homo sapiens, Homo sapiens (O75173)

11278559

638962

Flannery, C.R.; Zeng, W.; Corcoran, C.; Collins-Racie, L.A.; Chockalingam, P.S.; Hebert, T.; Mackie, S.A.; McDonagh, T.; Crawford, T.K.; Tomkinson, K.N.; LaVallie, E.R.; Morris, E.A.

Autocatalytic cleavage of ADAMTS-4 (aggrecanase-1) reveals multiple glycosaminoglycan-binding sites

J. Biol. Chem.

277

42775-42780

2002

Homo sapiens (O75173)

12202483

638963

Westling, J.; Fosang, A.J.; Last, K.; Thompson, V.P.; Tomkinson, K.N.; Hebert, T.; McDonagh, T.; Collins-Racie, L.A.; LaVallie, E.R.; Morris, E.A.; Sandy, J.D.

ADAMTS4 cleaves at the aggrecanase site (Glu373-Ala374) and secondarily at the matrix metalloproteinase site (Asn341-Phe342) in the aggrecan interglobular domain

J. Biol. Chem.

277

16059-16066

2002

Homo sapiens, Homo sapiens (O75173)

11854269

638964

Gao, G.; Westling, J.; Thompson, V.P.; Howell, T.D.; Gottschall, P.E.; Sandy, J.D.

Activation of the proteolytic activity of ADAMTS4 (aggrecanase-1) by C-terminal truncation

J. Biol. Chem.

277

11034-11041

2002

Homo sapiens, Homo sapiens (O75173), Sus scrofa

11796708

638965

Tortorella, M.D.; Liu, R.Q.; Burn, T.; Newton, R.C.; Arner, E.

Characterization of human aggrecanase 2 (ADAM-TS5): substrate specificity studies and comparison with aggrecanase 1 (ADAM-TS4)

Matrix Biol.

21

499-511

2002

Homo sapiens, Homo sapiens (O75173)

12392761

Chockalingam, P.S.; Zeng, W.; Morris, E.A.; Flannery, C.R.

Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5 (aggrecanase 2)

Arthritis Rheum.

50

2839-2848

2004

Homo sapiens

15457452

667360

Behera, A.K.; Hildebrand, E.; Szafranski, J.; Hung, H.H.; Grodzinsky, A.J.; Lafyatis, R.; Koch, A.E.; Kalish, R.; Perides, G.; Steere, A.C.; Hu, L.T.

Role of aggrecanase 1 in Lyme arthritis

Arthritis Rheum.

54

3319-3329

2006

Bos taurus, Homo sapiens, Mus musculus, Mus musculus C3H/HEN

17009305

667400

Liacini, A.; Sylvester, J.; Zafarullah, M.

Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes

Biochem. Biophys. Res. Commun.

327

320-327

2005

Homo sapiens

15629465

667468

Westling, J.; Gottschall, P.E.; Thompson, V.P.; Cockburn, A.; Perides, G.; Zimmermann, D.R.; Sandy, J.D.

ADAMTS4 (aggrecanase-1) cleaves human brain versican V2 at Glu405-Gln406 to generate glial hyaluronate binding protein

Biochem. J.

377

787-795

2004

Homo sapiens

14561220

Yoshida, K.; Suzuki, Y.; Saito, A.; Fukuda, K.; Hamanishi, C.; Munakata, H.

Aggrecanase-1 (ADAMTS-4) interacts with a1-antitrypsin

Biochim. Biophys. Acta

1725

152-159

2005

Homo sapiens

16099106

667826

Miwa, H.E.; Gerken, T.A.; Huynh, T.D.; Flory, D.M.; Hering, T.M.

Mammalian expression of full-length bovine aggrecan and link protein: Formation of recombinant proteoglycan aggregates and analysis of proteolytic cleavage by ADAMTS-4 and MMP-13

Biochim. Biophys. Acta

1760

472-486

2006

Homo sapiens

16427204

Noe, M.C.; Natarajan, V.; Snow, S.L.; Mitchell, P.G.; Lopresti-Morrow, L.; Reeves, L.M.; Yocum, S.A.; Carty, T.J.; Barberia, J.A.; Sweeney, F.J.; Liras, J.L.; Vaughn, M.; Hardink, J.R.; Hawkins, J.M.; Tokar, C.

Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13

Bioorg. Med. Chem. Lett.

15

2808-2811

2005

Homo sapiens

15911259

668117

Cross, A.K.; Haddock, G.; Stock, C.J.; Allan, S.; Surr, J.; Bunning, R.A.; Buttle, D.J.; Woodroofe, M.N.

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

Brain Res.

1088

19-30

2006

Homo sapiens, Rattus norvegicus

16630594

668982

Held-Feindt, J.; Paredes, E.B.; Bloemer, U.; Seidenbecher, C.; Stark, A.M.; Mehdorn, H.M.; Mentlein, R.

Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Int. J. Cancer

118

55-61

2005

Homo sapiens

16003758

Gao, G.; Plaas, A.; Thompson, V.P.; Jin, S.; Zuo, F.; Sandy, J.D.

ADAMTS4 (aggrecanase-1) activation on the cell surface involves C-terminal cleavage by glycosylphosphatidyl inositol-anchored membrane type 4-matrix metalloproteinase and binding of the activated proteinase to chondroitin sulfate and heparan sulfate on syndecan-1

J. Biol. Chem.

279

10042-10051

2004

Homo sapiens

14701864

670120

Wainwright, S.D.; Bondeson, J.; Hughes, C.E.

An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients

Matrix Biol.

25

317-320

2006

Homo sapiens

16723216

670737

Cross, N.A.; Chandrasekharan, S.; Jokonya, N.; Fowles, A.; Hamdy, F.C.; Buttle, D.J.; Eaton, C.L.

The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican

Prostate

63

269-275

2005

Homo sapiens

15599946

677881

Song, R.H.; Tortorella, M.D.; Malfait, A.M.; Alston, J.T.; Yang, Z.; Arner, E.C.; Griggs, D.W.

Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5

Arthritis Rheum.

56

575-585

2007

Homo sapiens

17265492

677894

Wagsaeter, D.; Bjoerk, H.; Zhu, C.; Bjoerkegren, J.; Valen, G.; Hamsten, A.; Eriksson, P.

ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques

Atherosclerosis

196

514-522

2008

Homo sapiens

17606262

El Mabrouk, M.; Sylvester, J.; Zafarullah, M.

Signaling pathways implicated in oncostatin M-induced aggrecanase-1 and matrix metalloproteinase-13 expression in human articular chondrocytes

Biochim. Biophys. Acta

1773

309-320

2007

Homo sapiens

17208315

Bondeson, J.; Wainwright, S.; Hughes, C.; Caterson, B.

The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review

Clin. Exp. Rheumatol.

26

139-145

2008

Bos taurus, Homo sapiens, Mus musculus, Sus scrofa

18328163

Hills, R.; Mazzarella, R.; Fok, K.; Liu, M.; Nemirovskiy, O.; Leone, J.; Zack, M.D.; Arner, E.C.; Viswanathan, M.; Abujoub, A.; Muruganandam, A.; Sexton, D.J.; Bassill, G.J.; Sato, A.K.; Malfait, A.M.; Tortorella, M.D.

Identification of an ADAMTS-4 cleavage motif using phage display leads to the development of fluorogenic peptide substrates and reveals matrilin-3 as a novel substrate

J. Biol. Chem.

282

11101-11109

2007

Homo sapiens

17311924

Lauer-Fields, J.L.; Minond, D.; Sritharan, T.; Kashiwagi, M.; Nagase, H.; Fields, G.B.

Substrate conformation modulates aggrecanase (ADAMTS-4) affinity and sequence specificity. Suggestion of a common topological specificity for functionally diverse proteases

J. Biol. Chem.

282

142-150

2007

Homo sapiens

17095512

680781

Gendron, C.; Kashiwagi, M.; Lim, N.H.; Enghild, J.J.; Thogersen, I.B.; Hughes, C.; Caterson, B.; Nagase, H.

Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4

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Homo sapiens

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Wayne, G.J.; Deng, S.J.; Amour, A.; Borman, S.; Matico, R.; Carter, H.L.; Murphy, G.

TIMP-3 inhibition of ADAMTS-4 (aggrecanase-1) is modulated by interactions between aggrecan and the C-terminal domain of ADAMTS-4

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Homo sapiens

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Fushimi, K.; Troeberg, L.; Nakamura, H.; Lim, N.H.; Nagase, H.

Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity

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Mosyak, L.; Georgiadis, K.; Shane, T.; Svenson, K.; Hebert, T.; McDonagh, T.; Mackie, S.; Olland, S.; Lin, L.; Zhong, X.; Kriz, R.; Reifenberg, E.L.; Collins-Racie, L.A.; Corcoran, C.; Freeman, B.; Zollner, R.; Marvell, T.; Vera, M.; Sum, P.E.; Lavallie, E.R.; Stahl, M.; Somers, W.

Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5

Protein Sci.

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Homo sapiens

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Yatabe, T.; Mochizuki, S.; Takizawa, M.; Chijiiwa, M.; Okada, A.; Kimura, T.; Fujita, Y.; Matsumoto, H.; Toyama, Y.; Okada, Y.

Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic chondrocytes

Ann. Rheum. Dis.

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Pockert, A.J.; Richardson, S.M.; Le Maitre, C.L.; Lyon, M.; Deakin, J.A.; Buttle, D.J.; Freemont, A.J.; Hoyland, J.A.

Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration

Arthritis Rheum.

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Homo sapiens

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Miwa, H.E.; Gerken, T.A.; Huynh, T.D.; Duesler, L.R.; Cotter, M.; Hering, T.M.

Conserved sequence in the aggrecan interglobular domain modulates cleavage by ADAMTS-4 and ADAMTS-5

Biochim. Biophys. Acta

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2009

Homo sapiens

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Hamel, M.G.; Ajmo, J.M.; Leonardo, C.C.; Zuo, F.; Sandy, J.D.; Gottschall, P.E.

Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extension

Exp. Neurol.

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Takizawa, M.; Yatabe, T.; Okada, A.; Chijiiwa, M.; Mochizuki, S.; Ghosh, P.; Okada, Y.

Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes

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Homo sapiens

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Demircan, K.; Gunduz, E.; Gunduz, M.; Beder, L.B.; Hirohata, S.; Nagatsuka, H.; Cengiz, B.; Cilek, M.Z.; Yamanaka, N.; Shimizu, K.; Ninomiya, Y.

Increased mRNA expression of ADAMTS metalloproteinases in metastatic foci of head and neck cancer

Head Neck

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Homo sapiens

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Ahmad, R.; Sylvester, J.; Ahmad, M.; Zafarullah, M.

Adaptor proteins and Ras synergistically regulate IL-1-induced ADAMTS-4 expression in human chondrocytes

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Homo sapiens

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Frank, J.E.; Thompson, V.P.; Brown, M.P.; Sandy, J.D.

Removal of O-linked and N-linked oligosaccharides is required for optimum detection of NITEGE neoepitope on ADAMTS4-digested fetal aggrecans: implications for specific N-linked glycan-dependent aggrecanolysis at Glu373-Ala374

Osteoarthritis Cartilage

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2008

Homo sapiens (O75173), Homo sapiens

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Cheung, K.S.; Hashimoto, K.; Yamada, N.; Roach, H.I.

Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation

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Homo sapiens (O75173), Homo sapiens

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Willems, S.H.; Tape, C.J.; Stanley, P.L.; Taylor, N.A.; Mills, I.G.; Neal, D.E.; McCafferty, J.; Murphy, G.

Thiol isomerases negatively regulate the cellular shedding activity of ADAM17

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Homo sapiens

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Lim, N.H.; Kashiwagi, M.; Visse, R.; Jones, J.; Enghild, J.J.; Brew, K.; Nagase, H.

Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications

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Homo sapiens

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Zha, Y.; Chen, Y.; Xu, F.; Li, T.; Zhao, C.; Cui, L.

ADAMTS4 level in patients with stable coronary artery disease and acute coronary syndromes

Biomed. Pharmacother.

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Homo sapiens

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Cappelli, A.; Nannicini, C.; Valenti, S.; Giuliani, G.; Anzini, M.; Mennuni, L.; Giordani, A.; Caselli, G.; Stasi, L.P.; Makovec, F.; Giorgi, G.; Vomero, S.

Design, synthesis, and preliminary biological evaluation of pyrrolo[3,4-c]quinolin-1-one and oxoisoindoline derivatives as aggrecanase inhibitors

ChemMedChem

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Homo sapiens

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Tortorella, M.D.; Tomasselli, A.G.; Mathis, K.J.; Schnute, M.E.; Woodard, S.S.; Munie, G.; Williams, J.M.; Caspers, N.; Wittwer, A.J.; Malfait, A.M.; Shieh, H.S.

Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors

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Steinmeyer, J.; Kordelle, J.; Stuerz, H.

In vitro inhibition of aggrecanase activity by tetracyclines and proteoglycan loss from osteoarthritic human articular cartilage

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Homo sapiens

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Troeberg, L.; Fushimi, K.; Scilabra, S.D.; Nakamura, H.; Dive, V.; Thogersen, I.B.; Enghild, J.J.; Nagase, H.

The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP-3

Matrix Biol.

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Homo sapiens

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Hu, Y.; Xing, L.; Thomason, J.R.; Xiang, J.; Ipek, M.; Guler, S.; Li, H.; Sabatini, J.; Chockalingam, P.; Reifenberg, E.; Sheldon, R.; Morris, E.A.; Georgiadis, K.E.; Tam, S.

Continued exploration of biphenylsulfonamide scaffold as a platform for aggrecanase-1 inhibition

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Homo sapiens

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Hsu, Y.P.; Staton, C.A.; Cross, N.; Buttle, D.J.

Anti-angiogenic properties of ADAMTS-4 in vitro

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ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis

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Filou, S.; Stylianou, M.; Triantaphyllidou, I.E.; Papadas, T.; Mastronikolis, N.S.; Goumas, P.D.; Papachristou, D.J.; Ravazoula, P.; Skandalis, S.S.; Vynios, D.H.

Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma

Biochimie

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Homo sapiens (O75173), Homo sapiens

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Obika, M.; Vernon, R.; Gooden, M.; Braun, K.; Chan, C.; Wight, T.

ADAMTS-4 and biglycan are expressed at high levels and co-localize to podosomes during endothelial cell tubulogenesis in vitro

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Durham, T.; Klimkowski, V.; Rito, C.; Marimuthu, J.; Toth, J.; Liu, C.; Durbin, J.; Stout, S.; Adams, L.; Swearingen, C.; Lin, C.; Chambers, M.; Thirunavukkarasu, K.; Wiley, M.

Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis

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Filomia, F.; Saxena, P.; Durante, C.; De Rienzo, F.; Cocchi, M.; Menziani, M.

Computational insights into ADAMTS4, ADAMTS5 and MMP13 inhibitor selectivity

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Homo sapiens (O75173)

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Wang, Z.; Luo, J.; Iwamoto, S.; Chen, Q.

Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5

Molecules

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Homo sapiens (O75173), Homo sapiens

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Roberts, S.; Evans, H.; Wright, K.; van Niekerk, L.; Caterson, B.; Richardson, J.; Kumar, K.; Kuiper, J.

ADAMTS-4 activity in synovial fluid as a biomarker of inflammation and effusion

Osteoarthritis Cartilage

23

1622-1626

2015

Homo sapiens (O75173)

26003949