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Information on EC 3.4.24.B12 - ADAMTS5 endopeptidase and Organism(s) Homo sapiens and UniProt Accession Q9UNA0
for references in articles please use BRENDA:EC3.4.24.B12preliminary BRENDA-supplied EC number
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3.4.24.B12 ADAMTS5 endopeptidaseSpecify your search results
Word Map
- 3.4.24.B12
- cartilage
- osteoarthritis
- chondrocytes
-
articular
- metalloproteinase
- collagen
- joint
-
disintegrin
- degeneration
- adamts-4
- tnf
- proteoglycans
- knee
-
intervertebral
-
degener
- synovial
- cox-2
- mmp-1
-
col2a1
- pulposus
- meniscus
- interleukin-1
-
intra-articular
- versican
-
disintegrin-like
- timp-3
-
temporomandibular
-
subchondral
-
safranin
-
cruciate
-
matrix-degrading
-
neoepitope
-
chondroprotective
-
chondrogenic
- brevican
- medicine
-
mankin
-
surgically-induced
-
oa-like
-
collagen-ii
-
meniscectomy
-
anti-catabolic
-
cartilage-degrading
-
interglobular
-
dmm-induced
-
condylar
-
oa-related
-
oa-associated
- osteophyte
-
motifs-4
-
osteoarthritis-like
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
adamts-5, adamts5, aggrecanase-2, adam-ts5, aggrecanase 2, aggrecanase-, adamts11, agg-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADAMTS-5
ADAMTS-5-2
ADAMTS-5 which lacks the C-terminal cysteine-rich spacer and thrombospondin domains
a disintegrin and metalloproteinase with thrombospondin motifs 5
ADAMTS-5
ADAMTS5
aggrecanase-2
-
-
ADAMTS-5
a disintegrin and metalloproteinase with thrombospondin motifs-5
a disintegrin and metalloproteinase with thrombospondin motifs 5
-
-
ADAMTS-5
-
-
ADAMTS-5
a disintegrin and metalloproteinase with thrombospondin motifs-5
ADAMTS5
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
strict specificity for cleavage between glutamic acid and uncharged aliphatic amino acids in the core proteins of large aggregating proteoglycans
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis
endoproteolytic cleavage of specific Glu-Xaa bonds within the core protein of aggrecan
CAS REGISTRY NUMBER
COMMENTARY
405150-12-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
aggrecan + H2O
7 aggregan fragment
several cleavage sites are determined
product determination, overview
?
K-[6FAM]-DVQEFRGVTAVIRC-[Qsy9]-KGK + H2O
K-[6FAM]-DVQE + FRGVTAVIRC-[Qsy9]-KGK
-
-
-
?
matrilin-2 + H2O
?
-
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
-
?
FAM-AELQGRPISIAK-TAMRA + H2O
?
-
activity measured using a quenched fluorescent substrate
-
-
?
K(6FAM)-DVQEFRGVTAVIRC(Qsy9)-KGK + H2O
K-(6FAM)-DVQE + FRGVTAVIRC(Qsy9)-KGK
-
-
-
-
?
o-aminobenzoyl-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-(N-3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-Lys-Lys-NH2 + H2O
o-aminobenzoyl-Thr-Glu-Ser-Glu + Ser-Arg-Gly-Ala-Ile-Tyr-(N-3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-Lys-Lys-NH2
-
recombinant ADAMTS-5 cleaves this substrate more readily than ADAMTS-4 in vitro
-
-
?
VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG + H2O
?
-
43mer peptide substrate
-
-
?
aggrecan + H2O
?
ADAMTS-4 and ADAMTS-5 are the proteases responsible for the endogenous aggrecanase activity observed in IL-1beta stimulated bovine cartilage
-
-
?
aggrecan + H2O
?
cleavage at the Glu373-Ala374 site of aggrecan is measured
-
-
?
proteins + H2O
peptides
strict specificity for cleavage between glutamic acid and uncharged aliphatic amino acids in the core proteins of large aggregating proteoglycans
-
?
aggrecan + H2O
?
-
-
-
-
?
aggrecan + H2O
?
-
cleavage site is Glu373-Ala374, other cleavage sites are Glu1545-Gly1546, Glu1819-Ala1820, and Glu1919-Leu1920
-
?
aggrecan + H2O
?
-
substrate from cartilage, extensive digestion, N-terminal cleavage sites between glutamate and small uncharged aliphatic amino acids in nonglycosylated regions of the aggregan core protein: the interglobular domain E373-A, and between chondroitin sulfate attachment sites 1 and 2 E1480-G
-
?
aggrecan + H2O
?
-
ADAMTS-5 is able to cleave aggrecan core protein about 1,000 times more effectively than ADAMTS-4
-
-
?
aggrecan + H2O
?
-
2 microg, 90 min, reaction stopped by addition of 21 mM EDTA
-
-
?
aggrecan + H2O
?
-
aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis, a degenerative joint disease that leads to the progressive destruction of articular structures
-
-
?
aggrecan + H2O
?
-
recombinant bovine aggrecan mutated at amino acids N-terminal or C-terminal to the interglobular domain cleavage site. Identification of multiple conserved amino acids within regions N- and C-terminal to the site of scission that may influence enzyme-substrate recognition, and may interact with exosites on ADAMTS-5. The S377Q mutant is extremely resistant to cleavage at Glu373-Ala374 by ADAMTS-5. Cleavage of S377T with ADAMTS-5 is also significantly inhibited compared to wild-type. The other P4'-mutant digests are similar to wild-type. Gln or Thr at the P4' position are inhibitory to ADAMTS-5 cleavage
-
-
?
aggrecan + H2O
?
-
ADAMTS5 is the most active aggrecanase compared to ADAMTS4 and is responsible for the generation of an oncostatin M-specific degradation pattern in the CS-2 region. ADAMTS5 has the ability to cleave at the oncostatin M-specific site adjacent to the aggrecan G3 region (Glu373-Ala374 bond). Truncation of the C-terminal TS domain or Sp domain does not affect the ability of the enzyme to cleave at this site
-
-
?
aggrecan-interglobular domain + H2O
?
-
an aggrecan peptide with the N-terminal sequence ARGSVIL is released and quantified
-
-
?
aggrecan-interglobular domain + H2O
?
-
cleavage site Glu373-Ala374 in aggrecaninterglobular domain
-
-
?
additional information
?
-
recombinant protein substrate based on the IGD (interglobular domain) of aggrecan, gst-IGD-flag
-
-
?
additional information
?
-
-
recombinant protein substrate based on the IGD (interglobular domain) of aggrecan, gst-IGD-flag
-
-
?
additional information
?
-
-
interaction with sulfated glucosaminglycan may be very important for the localization and activity of the enzymew
-
?
additional information
?
-
-
ADAMTS-5 shows proteolytic activity by second TS domain and little by catalytic domain alone and exhibits 1000fold greater strength of proteolytic activities as compared to ADAMTS-4
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
aggrecan + H2O
?
ADAMTS-4 and ADAMTS-5 are the proteases responsible for the endogenous aggrecanase activity observed in IL-1beta stimulated bovine cartilage
-
-
?
aggrecan + H2O
?
-
aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis, a degenerative joint disease that leads to the progressive destruction of articular structures
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[5-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-([[4'-(dimethylamino)biphenyl-4-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-([[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-([[6-(4-chlorophenyl)pyridin-3-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-2-ylethyl)amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-3-ylethyl)amino]-2-phenylcyclopropanecarboxylate
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-4-ylethyl)amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-1,2,3-triazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-1,2,4-triazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-imidazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-tetrazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2,5-dioxopyrrolidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxo-1,3-oxazinan-3-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxopiperidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2H-1,2,3-triazol-2-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(3-methoxy-2-oxopyridin-1(2H)-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(4H-1,2,4-triazol-4-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(7H-purin-7-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(9H-purin-9-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
-
(2R)-2-[4-(1,3-benzodioxol-5-yl)benzyl]-N4-hydroxy-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
nanomolar inhibitor of both ADAMTS-5
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
(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-optimize 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-(4-acetylphenoxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]acetamide
-
2-(benzyloxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]acetamide
-
2-(benzyloxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]acetamide
-
2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]acetamide
-
2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]acetamide
-
2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]acetamide
-
3-[2-[(Z)-(4-oxo-1,3-thiazolidin-2-ylidene)methyl]-4-(pyridin-2-yl)-1,3-thiazol-5-yl]propanoic acid
inhibits the spontaneous aggrecan degradation in IL-1-stimulated bovine cartilage, shows good selectivity over other metalloproteases
calcium pentosan polysulfate
chemically sulfated xylopyranose from beechwood. Multifaceted exosite inhibitor, protects cartilage against aggrecan degradation. Inhibitor interacts with the noncatalytic spacer domain of isoform ADAMTS-4 and the cysteine-rich domain of ADAMTS-5, blocking activity against their natural substrate aggrecan with inhibitory concentration 50 values of 10-40 nM but only weakly inhibiting hydrolysis of a nonglycosylated recombinant protein substrate. calcium pentosan polysulfate increases cartilage levels of tissue inhibitor of metalloproteinases TIMP-3, an endogenous inhibitor of ADAMTS-4 and -5
-
catechin gallate esters
from green tea Camellia sinensis, strong inhibition, independent of Zn2+, reversible
-
N-benzyl-N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-D-phenylalanine
30% inhibition at 0.01 mM
N-hydroxy-4-(4-(4-(trifluoromethyl)-phenoxy)phenylsulfonyl)-tetrahydro-2H-pyran-4-carboxamide
nanomolar inhibitor of both ADAMTS-5
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 metalloproteinaseP-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-chlorophenyl)(8-hydroxy-5-methylquinolin-7-yl)methyl]-2-phenoxyacetamide
-
N-[(2-chlorophenyl)(8-hydroxy-5-nitroquinolin-7-yl)methyl]-2-phenoxyacetamide
-
N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-N-(cyclohexylmethyl)-D-phenylalanine
22% inhibition at 0.01 mM
N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-N-(cyclopropylmethyl)-D-phenylalanine
46% inhibition at 0.01 mM
N-[(5-bromo-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-bromo-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-methyl-N2-phenylglycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-cyanophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-fluorophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-methylphenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-nitrophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-methyl-N2-phenylglycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-(pyridin-3-yloxy)acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-methyl-N2-phenylglycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-chlorophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(4-methoxyphenoxy)acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(4-methylphenoxy)acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(pyridin-3-yloxy)acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-(4-cyanophenyl)glycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-methyl-N2-phenylglycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-[3-(dimethylamino)phenyl]glycinamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-nitrophenyl)methyl]-2-phenoxyacetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-(4-chlorophenoxy)acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-(4-methylphenoxy)acetamide
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)[2-(trifluoromethyl)phenyl]methyl]-2-phenoxyacetamide
-
N-[(8-hydroxy-5-methylquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide
-
N2-(4-acetylphenyl)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]glycinamide
-
N2-(4-acetylphenyl)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]glycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-methylglycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]glycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-methylglycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]glycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-methylglycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-methylglycinamide
-
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]glycinamide
-
N2-[4-(acetylamino)phenyl]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]glycinamide
-
(1R,2R,3S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2,3-dimethylcyclopropanecarboxylate
-
-
(1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylate
-
-
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl]amino]-2-phenylcyclopropanecarboxylate
-
-
(1S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2,2-dimethylcyclopropanecarboxylate
-
0.001 mM, 19.6% inhibition
(1S,2R)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylate
-
0.0003 mM, 18% inhibition
(1S,2R)-1-([[5-(2-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
-
0.001 mM, 48% inhibition
(1S,2R)-1-([[5-(3-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-(propan-2-yl)cyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-cyclohexylcyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methyl-2-phenylcyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-2-phenylcyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
-
-
(1S,2R)-1-([[5-(5-chloropyridin-2-yl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
-
-
(1S,2R)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl]amino]-2-phenylcyclopropanecarboxylate
-
-
(1S,2R,3R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate
-
-
(1S,2R,3R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate
-
-
(1S,2S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methylcyclopropanecarboxylate
-
0.001 mM, 3.5% inhibition
(1S,2S)-2-benzyl-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)cyclopropanecarboxylate
-
0.001 mM, 25% inhibition
(1S,2S,3R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate
-
-
(2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide
-
-
(5E)-2-thioxo-5-([3-[3-(trifluoromethyl)phenoxy]phenyl]methylidene)-1,3-thiazolidin-4-one
-
-
(5E)-3-benzyl-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-([3-methoxy-4-[(4-methoxybenzyl)oxy]phenyl]methylidene)-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-([4-[(4-chlorobenzyl)oxy]-3-methoxyphenyl]methylidene)-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-ethyl-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-phenyl-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3,5-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3-(4-methoxyphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3-(4-methylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5E)-5-[[4-(benzyloxy)-3-methoxyphenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one
-
-
(5Z)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-1-methyl-2-thioxoimidazolidin-4-one
-
-
(5Z)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one
-
-
(S)-2-dimethylamino-N-hydroxy-3,3-dimethyl-4-[(4-phenoxyphenyl)-sulfonyl]-butanamide
-
SC81956, potent inhibitor of ADAMTS-5
1-benzyl-4-((4-(4-chlorophenoxy) phenyl)-sulfonyl)-N-hydroxypiperidine-4-carboxamide
multi-MMP inhibitor
2-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-methylbutanoic acid
-
-
2-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
-
2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-methylbutanoic acid
-
-
2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
-
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-1Hpyrrolo[3,4-c]quinoline-4-carboxamide
-
-
2-[4-(benzyloxy)phenyl]-3-oxoisoindoline-4-carboxylic acid
-
does not inhibit ADAMTS-4
2-[4-(benzyloxy)phenyl]-N-hydroxy-3-oxoisoindoline-4-carboxamide
-
does not inhibit ADAMTS-4
3-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
3-[2-[(Z)-(4-oxo-1,3-thiazolidin-2-ylidene)methyl]-4-(pyridin-2-yl)-1,3-thiazol-5-yl]propanoic acid
inhibits the spontaneous aggrecan degradation in IL-1-stimulated bovine cartilage, shows good selectivity over other metalloproteases
4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-phenyl-5-(2-pyrimidin-1(6H)-ylpiperazin-1-yl)-1H-pyrazole-1-carbonitrile
-
-
4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-5-(2-pyrimidin-1(6H)-ylpiperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazole-1-carbonitrile
-
-
5-([1,3-diphenyl-5-[(thiophen-2-ylmethyl)sulfanyl]-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([1-methyl-5-[(2H-thiopyran-2-ylmethyl)sulfanyl]-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
40% inhibition at 0.02 mM
5-([1-methyl-5-[(4-methylphenyl)sulfanyl]-3-phenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([1-phenyl-5-[2-(tetrahydrothiophen-2-yl)ethoxy]-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(2-chlorobenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(4-chlorobenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(4-chlorobenzyl)sulfanyl]-1-phenyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(4-chlorophenyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
47% inhibition at 0.02 mM
5-([5-[(4-methoxybenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
53% inhibition at 0.02 mM
5-([5-[(4-tert-butylbenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(furan-2-ylmethyl)sulfanyl]-1,3-diphenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(furan-2-ylmethyl)sulfanyl]-1-methyl-3-phenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[(furan-2-ylmethyl)sulfanyl]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
42% inhibition at 0.02 mM
5-([5-[2-(4-chlorophenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[2-(4-fluorophenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[2-(4-methoxyphenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
31% inhibition at 0.02 mM
5-([5-[4-(4-chlorophenyl)piperazin-1-yl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-([5-[4-(4-chlorophenyl)piperazin-1-yl]-1-phenyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-[(4-chlorobenzyl)sulfanyl]-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carbonitrile
-
-
5-[(furan-2-ylmethyl)sulfanyl]-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-phenyl-1H-pyrazole-1-carbonitrile
-
-
5-[[1-methyl-5-(phenylsulfanyl)-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methylen]-2-thioxo-1,3-thiazolidin-4-one
-
28% inhibition at 0.02 mM
5-[[5-(4-methylpiperazin-1-yl)-1,3-diphenyl-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one
-
-
5-[[5-(4-methylpiperazin-1-yl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one
-
45% inhibition at 0.02 mM
5-[[5-(benzylsulfanyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one
-
44% inhibition at 0.02 mM
5-[[5-(benzylsulfanyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one
-
-
aggrecanase inhibitor BB-16
-
prevents aggrecan degradation in osteoarthritic cartilage
BB-16
-
(2S,5R,6S)-3-Aza-4-oxo-10-oxa-5-hexyl-2-(methylcarboxamido)-10-paracyclophane-6-N-hydroxycarboxamide
N-hydroxy-4-([4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
-
-
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
all isoforms of ADAMTS-5 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-[(1R)-1-(dihydroxymethyl)-2-methylpropyl]-4'-{[4-(2-methylpropanoyl)phenoxy]methyl}biphenyl-4-sulfonamide
-
-
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
[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl](phenyl)acetic acid
-
-
[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl](phenyl)acetic acid
-
-
[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
-
(2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
the reduced pattern of H-bond interactions is suitable for the flexible environment of ADAMTS4 and ADAMTS5 since it enables the inhibitor to re-optimize 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
(E)-2-((1H-benzo[d]imidazol-2-yl)methylene)-5-propylthiazolidin-4-one
potent small-molecule ADAMTS-5 inhibitor with good permeability
alpha2-Macroglobulin
-
after 10 min 100% and 68% inhibition at concentrations of 2.5 and 7.5 nM, respectively, similar results when using 25 and 75 nM
-
TIMP-3
-
recombinant human inhibitor protein from Escherichia coli, i.e. tissue inhibitor of metalloproteinases, strong inhibitor with regulatory function
-
tissue inhibitor of metalloproteinases-3
-
all isoforms of ADAMTS-5 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
-
additional information
design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5
-
additional information
-
no inhibition by matrix metalloprotease inhibitor XS309
-
additional information
-
[3S-[3R*,2-[2R*,2-(R*,S*)]-hexahydro-2-(2-[2-(hydroxyamino)-1-methyl-2-oxyethyl])-4-methyl-1-oxypentyl]-N-methyl]-3-pyridazinecarboxamide, i.e.XS309 is inactive at less than 0.01 mM in blocking ADAMTS-5
-
additional information
-
the general proteolytic activitiy of ADAMTS-5 as measured with carboxymethylated transferrin is unaffected by concentrations up to 1 M NaCl
-
additional information
-
substrate specificity of ADAMTS-5 against recombinant aggrecan, aggrecan mutants S377Q and S377T lead to aggrecan cleavage inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
interleukin-1alpha
-
increased transcription in the presence of interleukin-1alpha
-
additional information
-
ADAMTS5 expression is not stimulated by interleukin-1, tumor necrosis factor alpha, oncostatin M or transforming growth factor beta
-
additional information
-
higher enzyme expression in degenerated intervertebral discs
-
additional information
-
higher expression level in metastatic foci compared with corresponding primary tumor
-
additional information
-
syndecan-4 controls the activation of ADAMTS-5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix metalloproteinase-3 (MMP-3). Syndecan-4 is crucial in regulating Mmp-3 expression by activating ERK1/2 and by targeting ADAMTS-5 to the cell surface of chondrocytes
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000093
(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
0.000017
(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
0.000106
marimastat
pH not specified in the publication, temperature not specified in the publication
0.00013
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-1
-
0.00029
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-3
-
0.00035
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-2
-
0.0004
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-4
-
0.00101
N-terminal domain of tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-5
-
0.00063
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-1
-
0.00072
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-2
-
0.001
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-3
-
0.00113
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-4
-
0.00117
tissue inhibitor of metalloproteinases-3
-
pH 7.5, 37°C, isoenzyme ADAMTS5-5
-
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
-
additional information
additional information
-
Ki(app) of N-terminal alanine-extension mutants and of position [-1] mutants of N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00007
(1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0002
(1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[5-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0045
(1R,2S)-1-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0066
(1R,2S)-1-([[4'-(dimethylamino)biphenyl-4-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00088
(1R,2S)-1-([[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0011
(1R,2S)-1-([[6-(4-chlorophenyl)pyridin-3-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00082
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-2-ylethyl)amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00029
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-3-ylethyl)amino]-2-phenylcyclopropanecarboxylate
Homo sapiens
-
0.00075
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-4-ylethyl)amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00027
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-1,2,3-triazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
Homo sapiens
-
0.00018
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-1,2,4-triazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0002
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-imidazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00027
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-tetrazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0001
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2,5-dioxopyrrolidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00018
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxo-1,3-oxazinan-3-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
Homo sapiens
-
0.00022
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00021
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxopiperidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.0002
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00026
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2H-1,2,3-triazol-2-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
Homo sapiens
-
0.00078
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(3-methoxy-2-oxopyridin-1(2H)-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate
Homo sapiens
-
0.00019
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(4H-1,2,4-triazol-4-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.000071
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(7H-purin-7-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.00017
(1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(9H-purin-9-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid
Homo sapiens
-
0.000129
(2R)-2-[4-(1,3-benzodioxol-5-yl)benzyl]-N4-hydroxy-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
Homo sapiens
pH and temperature not specified in the publication
0.000093
(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
0.000017
(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
0.00233
2-(4-acetylphenoxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]acetamide
Homo sapiens
-
0.00083
2-(benzyloxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]acetamide
Homo sapiens
-
0.0007
2-(benzyloxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]acetamide
Homo sapiens
-
0.00234
2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]acetamide
Homo sapiens
-
0.00133
2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]acetamide
Homo sapiens
-
0.00339
2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]acetamide
Homo sapiens
-
0.023
3-[2-[(Z)-(4-oxo-1,3-thiazolidin-2-ylidene)methyl]-4-(pyridin-2-yl)-1,3-thiazol-5-yl]propanoic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.129
N-hydroxy-4-(4-(4-(trifluoromethyl)-phenoxy)phenylsulfonyl)-tetrahydro-2H-pyran-4-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00242
N-[(2-chlorophenyl)(8-hydroxy-5-methylquinolin-7-yl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00094
N-[(2-chlorophenyl)(8-hydroxy-5-nitroquinolin-7-yl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00083
N-[(5-bromo-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00062
N-[(5-bromo-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00035
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
sub-micromol ADAMTS-5 potency and good selectivity over the related metalloproteases ADAMTS-4 (aggrecanase-1), MMP-13, and MMP-12
0.00172
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide
Homo sapiens
-
0.00148
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
Homo sapiens
-
0.00099
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-methyl-N2-phenylglycinamide
Homo sapiens
-
0.00232
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-cyanophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00122
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-fluorophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00185
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-methylphenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00121
N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-nitrophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00062
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00337
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide
Homo sapiens
-
0.00143
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
Homo sapiens
-
0.00125
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-methyl-N2-phenylglycinamide
Homo sapiens
-
0.00166
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-(pyridin-3-yloxy)acetamide
Homo sapiens
-
0.00049
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
sub-micromol ADAMTS-5 potency and good selectivity over the related metalloproteases ADAMTS-4 (aggrecanase-1), MMP-13, and MMP-12
0.00119
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
Homo sapiens
-
0.00056
N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-methyl-N2-phenylglycinamide
Homo sapiens
sub-micromol ADAMTS-5 potency and good selectivity over the related metalloproteases ADAMTS-4 (aggrecanase-1), MMP-13, and MMP-12. Good balance of potent ADAMTS-5 inhibition, moderate CYP3A4 inhibition and good rat liver microsome stability
0.00083
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-chlorophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00094
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(4-methoxyphenoxy)acetamide
Homo sapiens
sub-micromol ADAMTS-5 potency and good selectivity over the related metalloproteases ADAMTS-4 (aggrecanase-1), MMP-13, and MMP-12
0.00077
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(4-methylphenoxy)acetamide
Homo sapiens
-
0.00298
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(pyridin-3-yloxy)acetamide
Homo sapiens
-
0.00135
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00167
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide
Homo sapiens
-
0.00076
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00158
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide
Homo sapiens
-
0.00101
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-(4-cyanophenyl)glycinamide
Homo sapiens
-
0.00078
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-methyl-N2-phenylglycinamide
Homo sapiens
-
0.00193
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-[3-(dimethylamino)phenyl]glycinamide
Homo sapiens
-
0.00046
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-nitrophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00102
N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-(4-chlorophenoxy)acetamide
Homo sapiens
-
0.0019
N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-(4-methylphenoxy)acetamide
Homo sapiens
-
0.00078
N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00083
N-[(5-chloro-8-hydroxyquinolin-7-yl)[2-(trifluoromethyl)phenyl]methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00484
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00132
N-[(8-hydroxy-5-methylquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00135
N-[(8-hydroxy-5-nitroquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide
Homo sapiens
-
0.00107
N2-(4-acetylphenyl)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]glycinamide
Homo sapiens
-
0.00113
N2-(4-acetylphenyl)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]glycinamide
Homo sapiens
-
0.00131
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-methylglycinamide
Homo sapiens
-
0.00189
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]glycinamide
Homo sapiens
-
0.00144
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-methylglycinamide
Homo sapiens
-
0.00172
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]glycinamide
Homo sapiens
-
0.00082
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-methylglycinamide
Homo sapiens
-
0.00128
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-methylglycinamide
Homo sapiens
-
0.00183
N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]glycinamide
Homo sapiens
-
0.00277
N2-[4-(acetylamino)phenyl]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]glycinamide
Homo sapiens
-
0.0008
(1R,2R,3S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2,3-dimethylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.000073
(1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00021
(1S,2R)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.000094
(1S,2R)-1-([[5-(3-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00077
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-(propan-2-yl)cyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00036
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-cyclohexylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.000032
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methyl-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00008
(1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00001
(1S,2R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00006
(1S,2R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.0001
(1S,2R)-1-([[5-(5-chloropyridin-2-yl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.000084
(1S,2R)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl]amino]-2-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.0000074
(1S,2R,3R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.000021
(1S,2R,3R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.00012
(1S,2S,3R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate
Homo sapiens
-
pH and temperature not specified in the publication
0.0000014
(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
0.0053
(5E)-2-thioxo-5-([3-[3-(trifluoromethyl)phenoxy]phenyl]methylidene)-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.067
(5E)-3-benzyl-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.0116
(5E)-5-([3-methoxy-4-[(4-methoxybenzyl)oxy]phenyl]methylidene)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0035
(5E)-5-([4-[(4-chlorobenzyl)oxy]-3-methoxyphenyl]methylidene)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.022
(5E)-5-[(3-phenoxyphenyl)methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.022 mM
0.0018
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.067
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.067
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-ethyl-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.067
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.067
(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-phenyl-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.0014
(5E)-5-[[3,5-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0032
(5E)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0025
(5E)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0049 - 0.022
(5E)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
0.0162
(5E)-5-[[3-(4-methoxyphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0148
(5E)-5-[[3-(4-methylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0017
(5E)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0201
(5E)-5-[[3-(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.022
(5E)-5-[[4-(benzyloxy)-3-methoxyphenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.022 mM
0.01
(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0092
(5Z)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.067
(5Z)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.022
(5Z)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-1-methyl-2-thioxoimidazolidin-4-one
Homo sapiens
-
IC50 above 0.022 mM
0.067
(5Z)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.0068
(5Z)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.067
(5Z)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one
Homo sapiens
-
IC50 above 0.067 mM
0.00042
1-benzyl-4-((4-(4-chlorophenoxy) phenyl)-sulfonyl)-N-hydroxypiperidine-4-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0011
2-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-methylbutanoic acid
Homo sapiens
-
-
0.0013
2-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
Homo sapiens
-
-
0.0018
2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-methylbutanoic acid
Homo sapiens
-
-
0.0016
2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
Homo sapiens
-
-
0.012
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
0.00095
2-[4-(benzyloxy)phenyl]-2,3-dihydro-N-hydroxy-1-oxo-1Hpyrrolo[3,4-c]quinoline-4-carboxamide
Homo sapiens
-
37°C, pH and temperature not specified in the publication
0.0053
3-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Homo sapiens
-
-
0.00023
3-[2-[(Z)-(4-oxo-1,3-thiazolidin-2-ylidene)methyl]-4-(pyridin-2-yl)-1,3-thiazol-5-yl]propanoic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.008
4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-phenyl-5-(2-pyrimidin-1(6H)-ylpiperazin-1-yl)-1H-pyrazole-1-carbonitrile
Homo sapiens
-
-
0.0117
4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-5-(2-pyrimidin-1(6H)-ylpiperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazole-1-carbonitrile
Homo sapiens
-
-
0.0037
5-([1,3-diphenyl-5-[(thiophen-2-ylmethyl)sulfanyl]-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0083
5-([1-methyl-5-[(4-methylphenyl)sulfanyl]-3-phenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0091
5-([1-phenyl-5-[2-(tetrahydrothiophen-2-yl)ethoxy]-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0232
5-([5-[(2-chlorobenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0011
5-([5-[(4-chlorobenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0025
5-([5-[(4-chlorobenzyl)sulfanyl]-1-phenyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0022
5-([5-[(4-tert-butylbenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0067
5-([5-[(furan-2-ylmethyl)sulfanyl]-1,3-diphenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0141
5-([5-[(furan-2-ylmethyl)sulfanyl]-1-methyl-3-phenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0042
5-([5-[2-(4-chlorophenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0071
5-([5-[2-(4-fluorophenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.009
5-([5-[4-(4-chlorophenyl)piperazin-1-yl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0021
5-([5-[4-(4-chlorophenyl)piperazin-1-yl]-1-phenyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0042
5-[(4-chlorobenzyl)sulfanyl]-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carbonitrile
Homo sapiens
-
-
0.0046
5-[(furan-2-ylmethyl)sulfanyl]-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-phenyl-1H-pyrazole-1-carbonitrile
Homo sapiens
-
-
0.0046
5-[[5-(4-methylpiperazin-1-yl)-1,3-diphenyl-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.0169
5-[[5-(benzylsulfanyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.00029
N-hydroxy-4-([4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide
Homo sapiens
-
in 100 mM Tris-HCl, 100 mM NaCl, 0.01 mM CaCl2, 0.05% Brij, pH 7.5
0.000004 - 0.000035
N-[[(4S)-4-(1-methylimidazol-2-yl)-2,5-dioxo-imidazolidin-4-yl]methyl]-5-(trifluoromethyl)benzofuran-2-carboxamide
0.0011
N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine
Homo sapiens
-
37°C, pH and temperature not specified in the publication
0.0000038
TIMP-3
Homo sapiens
-
in 100 mM Tris-HCl, 100 mM NaCl, 0.01 mM CaCl2, 0.05% Brij, pH 7.5
-
0.0009
[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl](phenyl)acetic acid
Homo sapiens
-
-
0.0067
[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Homo sapiens
-
-
0.0013
[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl](phenyl)acetic acid
Homo sapiens
-
-
0.0111
[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Homo sapiens
-
-
0.00017
(E)-2-((1H-benzo[d]imidazol-2-yl)methylene)-5-propylthiazolidin-4-one
Homo sapiens
pH 7.5, 37°C
0.021
(E)-2-((1H-benzo[d]imidazol-2-yl)methylene)-5-propylthiazolidin-4-one
Homo sapiens
pH 7.5, 37°C
0.0049
(5E)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
-
0.022
(5E)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
-
IC50 above 0.022 mM
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
0.000035
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, presence of 50% rat plasma
additional information
additional information
Homo sapiens
inhibitors which show strong potency of IC50 with excellent selectivity over MMP-1 and TACE
-
additional information
2-[4-(benzyloxy)phenyl]-3-oxoisoindoline-4-carboxylic acid
Homo sapiens
-
IC25-value: 0.0075 mM, 37°C, pH and temperature not specified in the publication, plateau inhibition at about 50%
additional information
2-[4-(benzyloxy)phenyl]-N-hydroxy-3-oxoisoindoline-4-carboxamide
Homo sapiens
-
IC25-value: 0.0025 mM, 37°C, pH and temperature not specified in the publication, plateau inhibition at about 50%
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
ADAMTS-5 is the main aggrecanase in laryngeal squamous cell carcinoma
-
ADAMTS-4, EC 3.4.24.82, is the highest expressed aggrecanase in normal larynx
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
ADAMTS-5 knockout mice express no major phenotypical abnormalities, but show a significant reduction in the severity of surgically induced osteoarthritis in the ADAMTS-5 in contrast to the ADAMTS-4 knockout groups
malfunction
insufficiency of enzyme expression in Sertoli cells may have an important role in the etiology of male infertility
physiological function
-
aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis, a degenerative joint disease that leads to the progressive destruction of articular structures
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
-
key metalloprotease mediating cartilage destruction in arthritis
physiological function
-
ADAMTS-5 contributes to the structural damage of cartilage that characterizes human osteoarthritis
physiological function
-
overexpression of full-length ADAMTS5 suppresses B16 melanoma growth in mice. The reduced tumor growth is correlated with diminished tumor angiogenesis, together with reduced tumor cell proliferation and increased tumor cell apoptosis. Catalytically active ADAMTS5 proteolytic fragment also suppresses angiogenesis in vitro. The catalytic activity of ADAMTS5 is dispensable for its anti-tumorigenic function. ADAMTS5 inhibits B16 tumorigenesis through its TSR1 by suppressing tumor angiogenesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
64000
x * 64000, C-terminally processed recombinant mature enzyme, SDS-PAGE
74000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
recombinant enzyme is also processed in insect cells
glycoprotein
proteolytic modification
proteolytic modification
-
synthesized as a zymogen, proADAMTS5. The propeptide excision mechanism is a major regulatory step. proADAMTS5 is processed by proprotein convertases, specifically furin and PC7, but not PC6B. proADAMTS5 processing occurs after Arg261. Cleaved ADAMTS5 propeptide and mature ADAMTS5 are found exclusively in the conditioned medium. Extracellular ADAMTS5 processing is supported by activation of proADAMTS5 added exogenously to HEK-293 cells stably expressing furin
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ADAMTS-5 catalytic domain in complex with inhibitor, vapor diffusion method, using 30% (w/v) PEG 3350 and 0.1 M Tris pH 8.5, at 22°C
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
sitting drop method, crystal structure of the catalytic domain of ADAMTS-5 in complex with marimastat, (2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide or (3R)-N2-(cyclopropylmethyl)-N1-hydroxy-3-(3-hydroxybenzyl)-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-L-aspartamide
in complex with batimastat, vapour diffusion method at 18°C using 10% PEG 8K, 0.2 M ammonium sulfate, and 0.1M MES (pH 6.5) as a precipitate
-
vapour diffusion method with 25% (v/v) polyethylene glycol 3350, 200 mM ammonium acetate, 100 mM Tris, pH 8.5
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E411Q
full length ADAMTS-5 active site mutant generated by point mutation
E411A
-
active site mutant, presents similar tumor suppression activity as wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
anti-FLAG M2-agarose column chromatography, Macro-Prep 25 S resin chromatography, and
-
M2-agarose column chromatography, Macro-Prep S resin column chromatography, and Sephacryl S-200 gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
correction of point mutations G577S and Q579R by overlap extension PCR, subcloning from FLAG-tagged construct in the baculovirus, cloning and expression of His-FLAG-tagged wild-type enzyme and mutants in insect cells via baculovirus infection
expression of a recombinant interglobular domain of human aggrecan, residues 330YTGED to HLPGG458 tagged with glutathione S-transferase and FLAG, in Escherichia coli
the catalytic domain of ADAMTS-5 comprising amino acids S263 to I480 preceded by a Met-Ala sequence and incorporating the single point mutation L282K is expressed in Escherichia coli
expression of FLAG-tagged enzyme in Spodoptera frugiperda Sf9 cells via baculovirus infection, secretion of recombinant protein to the medium
-
the first thrombospondin type 1 repeat is expressed in Escherichia coli strain BL21DE3
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ADAMTS-5 expression is not regulated by interleukin-1 and tumor necrosis factor-alpha
-
interleukin-1beta+OSM and tumor necrosis factor alpha+ OSM treatments induces a 17fold and 13fold increase in ADAMTS5 gene expression. Relatively little modulation in ADAMTS5 expression is observed in the presence of interleukin-1beta, tumor necrosis factor alpha or OSM alone
-
the enzyme is expressed 2.1fold less in Sertoli cells of individuals with nonobstructive azoospermia than those of control individuals with obstructive azoospermia
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
in 50 mM HEPES, pH 8.0, 2 mM oxidized glutathione, 50 mM arginine, 10 mM CaCl2, 0.2 mM ZnCl2, and 1% protease inhibitors, at room temperature
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5, which may be required for chronic osteoarthritis therapy
medicine
additional information
-
neurite extension mediated by the MAP kinase pathway, increased number of primary and secondary neurites
medicine
-
the first thrombospondin type 1 repeat domain of ADAMTS5, unlike the second, has anti-angiogenic activities, ADAMTS5 is therefore an anti-angiogenic peptide and may serve as a prototype for future development into anti-cancer drugs
medicine
-
ADAMTS5 is a biomarker for prediction of response to Infliximab in patients with rheumatoid arthritis
medicine
-
ADAMTS-5 is the main aggrecanase in laryngeal squamous cell carcinoma presenting a stage-related increase up to stage III (8fold higher expression compared to normal), and thereafter decreased in stage IV. ADAMTS-5 is highly expressed by carcinoma cells. Within the cancerous and their corresponding macroscopically normal laryngeal tissues, an altered distribution and organization of multiple molecular forms (latent, activated and fragmented forms) of the enzymes is found
medicine
-
overexpression of full-length ADAMTS5 suppresses B16 melanoma growth in mice. The reduced tumor growth is correlated with diminished tumor angiogenesis, together with reduced tumor cell proliferation and increased tumor cell apoptosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Bos taurus (Q9TT92), Homo sapiens (Q9UNA0), Mus musculus (Q9R001)
Vankemmelbeke, M.N.; Holen, I.; Wilson, A.G.; Ilic, M.Z.; Handley, C.J.; Kelner, G.S.; Clark, M.; Liu, C.; Maki, R.A.; Burnett, D.; Buttle, D.J.
Expression and activity of ADAMTS-5 in synovium
Eur. J. Biochem.
268
1259-1268
2001
Homo sapiens, Bos taurus (Q9TT92), Bos taurus
Vankemmelbeke, M.N.; Jones, G.C.; Fowles, C.; Ilic, M.Z.; Handley, C.J.; Day, A.J.; Knight, C.G.; Mort, J.S.; Buttle, D.J.
Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters
Eur. J. Biochem.
270
2394-2403
2003
Homo sapiens (Q9UNA0)
Kashiwagi, M.; Tortorella, M.; Nagase, H.; Brew, K.
TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5)
J. Biol. Chem.
276
12501-12504
2001
Homo sapiens
Malfait, A.M.; Liu, R.Q.; Ijiri, K.; Komiya, S.; Tortorella, M.D.
Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage
J. Biol. Chem.
277
22201-22208
2002
Homo sapiens
Nakada, M.; Miyamori, H.; Kita, D.; Takahashi, T.; Yamashita, J.; Sato, H.; Miura, R.; Yamaguchi, Y.; Okada, Y.
Human glioblastomas overexpress ADAMTS-5 that degrades brevican
Acta Neuropathol.
110
239-246
2005
Homo sapiens (Q9UHI8), Homo sapiens
Zeng, W.; Corcoran, C.; Collins-Racie, L.A.; LaVallie, E.R.; Morris, E.A.; Flannery, C.R.
Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: Comparative analyses with ADAMTS-5, -9, -16 and -18
Biochim. Biophys. Acta
1760
517-524
2006
Homo sapiens (Q9UNA0), Homo sapiens
Miguel, R.F.; Pollak, A.; Lubec, G.
Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimers and Picks disease
Brain Res. Mol. Brain Res.
133
1-5
2005
Homo sapiens (Q9UHI8), Homo sapiens
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
Tortorella, M.D.; Arner, E.C.; Hills, R.; Easton, A.; Korte-Sarfaty, J.; Fok, K.; Wittwer, A.J.; Liu, R.Q.; Malfait, A.M.
Alpha2-macroglobulin is a novel substrate for ADAMTS-4 and ADAMTS-5 and represents an endogenous inhibitor of these enzymes
J. Biol. Chem.
279
17554-17561
2004
Homo sapiens
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
Sharghi-Namini, S.; Fan, H.; Sulochana, K.N.; Potturi, P.; Xiang, W.; Chong, Y.S.; Wang, Z.; Yang, H.; Ge, R.
The first but not the second thrombospondin type 1 repeat of ADAMTS5 functions as an angiogenesis inhibitor
Biochem. Biophys. Res. Commun.
371
215-219
2008
Homo sapiens
Bursavich, M.G.; Gilbert, A.M.; Lombardi, S.; Georgiadis, K.E.; Reifenberg, E.; Flannery, C.R.; Morris, E.A.
Synthesis and evaluation of aryl thioxothiazolidinone inhibitors of ADAMTS-5 (Aggrecanase-2)
Bioorg. Med. Chem. Lett.
17
1185-1188
2007
Homo sapiens
Gilbert, A.M.; Bursavich, M.G.; Lombardi, S.; Georgiadis, K.E.; Reifenberg, E.; Flannery, C.R.; Morris, E.A.
5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5
Bioorg. Med. Chem. Lett.
17
1189-1192
2007
Homo sapiens
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
Homo sapiens, Mus musculus
Fosang, A.J.; Rogerson, F.M.; East, C.J.; Stanton, H.
ADAMTS-5: the story so far
Eur. Cell Mater.
15
11-26
2008
Bos taurus, Homo sapiens, Mus musculus
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
J. Biol. Chem.
282
18294-18306
2007
Homo sapiens
Shieh, H.S.; Mathis, K.J.; Williams, J.M.; Hills, R.L.; Wiese, J.F.; Benson, T.E.; Kiefer, J.R.; Marino, M.H.; Carroll, J.N.; Leone, J.W.; Malfait, A.M.; Arner, E.C.; Tortorella, M.D.; Tomasselli, A.
High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2)
J. Biol. Chem.
283
1501-1507
2008
Homo sapiens
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
J. Biol. Chem.
283
6706-6716
2008
Homo sapiens
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.
17
16-21
2008
Homo sapiens
Gilbert, A.M.; Bursavich, M.G.; Lombardi, S.; Georgiadis, K.E.; Reifenberg, E.; Flannery, C.R.; Morris, E.A.
N-((8-hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2)
Bioorg. Med. Chem. Lett.
18
6454-6457
2008
Homo sapiens (Q9UNA0)
Shiozaki, M.; Maeda, K.; Miura, T.; Ogoshi, Y.; Haas, J.; Fryer, A.M.; Laird, E.R.; Littmann, N.M.; Andrews, S.W.; Josey, J.A.; Mimura, T.; Shinozaki, Y.; Yoshiuchi, H.; Inaba, T.
Novel N-substituted 2-phenyl-1-sulfonylamino-cyclopropane carboxylates as selective ADAMTS-5 (aggrecanase-2) inhibitors
Bioorg. Med. Chem. Lett.
19
1575-1580
2009
Homo sapiens (Q9UNA0)
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.
60
482-491
2009
Homo sapiens
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
1790
161-172
2009
Homo sapiens
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.
210
428-440
2008
Homo sapiens
Troeberg, L.; Fushimi, K.; Khokha, R.; Emonard, H.; Ghosh, P.; Nagase, H.
Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases
FASEB J.
22
3515-3524
2008
Homo sapiens (Q9UNA0)
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
FEBS Lett.
582
2945-2949
2008
Homo sapiens
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
10
793-801
2009
Homo sapiens
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
Biochem. J.
428
439-450
2010
Homo sapiens
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
Biochem. J.
431
113-122
2010
Homo sapiens (Q9UNA0), Homo sapiens
Shiozaki, M.; Imai, H.; Maeda, K.; Miura, T.; Yasue, K.; Suma, A.; Yokota, M.; Ogoshi, Y.; Haas, J.; Fryer, A.M.; Laird, E.R.; Littmann, N.M.; Andrews, S.W.; Josey, J.A.; Mimura, T.; Shinozaki, Y.; Yoshiuchi, H.; Inaba, T.
Synthesis and SAR of 2-phenyl-1-sulfonylaminocyclopropane carboxylates as ADAMTS-5 (aggrecanase-2) inhibitors
Bioorg. Med. Chem. Lett.
19
6213-6217
2009
Homo sapiens
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
5
739-748
2010
Homo sapiens
Longpre, J.; McCulloch, D.; Koo, B.; Alexander, J.; Apte, S.; Leduc, R.
Characterization of proADAMTS5 processing by proprotein convertases
Int. J. Biochem. Cell Biol.
41
1116-1126
2009
Homo sapiens
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
J. Biol. Chem.
284
24185-24191
2009
Homo sapiens (Q9UNA0)
Steinmeyer, J.; Kordelle, J.; Stuerz, H.
In vitro inhibition of aggrecanase activity by tetracyclines and proteoglycan loss from osteoarthritic human articular cartilage
J. Orthop. Res.
28
828-833
2010
Homo sapiens
Tsuzaka, K.; Itami, Y.; Takeuchi, T.; Shinozaki, N.; Morishita, T.
ADAMTS5 is a biomarker for prediction of response to infliximab in patients with rheumatoid arthritis
J. Rheumatol.
37
1454-1460
2010
Homo sapiens
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.
28
463-469
2009
Homo sapiens
Echtermeyer, F.; Bertrand, J.; Dreier, R.; Meinecke, I.; Neugebauer, K.; Fuerst, M.; Lee, Y.J.; Song, Y.W.; Herzog, C.; Theilmeier, G.; Pap, T.
Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis
Nat. Med.
15
1072-1076
2009
Homo sapiens
Durigova, M.; Troeberg, L.; Nagase, H.; Roughley, P.J.; Mort, J.S.
Involvement of ADAMTS5 and hyaluronidase in aggrecan degradation and release from OSM-stimulated cartilage
Eur. Cell Mater.
21
31-45
2011
Homo sapiens
Verma, P.; Dalal, K.
ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis
J. Cell. Biochem.
112
3507-3514
2011
Homo sapiens
Durigova, M.; Nagase, H.; Mort, J.S.; Roughley, P.J.
MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein
Matrix Biol.
30
145-153
2011
Homo sapiens
Shieh, H.S.; Tomasselli, A.G.; Mathis, K.J.; Schnute, M.E.; Woodard, S.S.; Caspers, N.; Williams, J.M.; Kiefer, J.R.; Munie, G.; Wittwer, A.; Malfait, A.M.; Tortorella, M.D.
Structure analysis reveals the flexibility of the ADAMTS-5 active site
Protein Sci.
20
735-744
2011
Homo sapiens (Q9UNA0)
Kumar, S.; Sharghi-Namini, S.; Rao, N.; Ge, R.
ADAMTS5 functions as an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity
Am. J. Pathol.
181
1056-1068
2012
Homo sapiens
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
95
725-734
2013
Homo sapiens
Atobe, M.; Maekawara, N.; Ishiguro, N.; Sogame, S.; Suenaga, Y.; Kawanishi, M.; Suzuki, H.; Jinno, N.; Tanaka, E.; Miyoshi, S.
A series of thiazole derivatives bearing thiazolidin-4-one as non-competitive ADAMTS-5 (aggrecanase-2) inhibitors
Bioorg. Med. Chem. Lett.
23
2106-2110
2013
Homo sapiens, Homo sapiens (Q9UNA0)
Sogame, S.; Suenaga, Y.; Atobe, M.; Kawanishi, M.; Tanaka, E.; Miyoshi, S.
Discovery of a benzimidazole series of ADAMTS-5 (aggrecanase-2) inhibitors by scaffold hopping
Eur. J. Med. Chem.
71
250-258
2014
Homo sapiens (Q9UNA0)
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
J. Med. Chem.
57
10476-10485
2014
Homo sapiens
Filomia, F.; Saxena, P.; Durante, C.; De Rienzo, F.; Cocchi, M.; Menziani, M.
Computational insights into ADAMTS4, ADAMTS5 and MMP13 inhibitor selectivity
Mol. Inform.
31
421-430
2012
Homo sapiens (Q9UNA0)
Wang, Z.; Luo, J.; Iwamoto, S.; Chen, Q.
Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5
Molecules
19
8472-8487
2014
Homo sapiens (Q9UNA0), Homo sapiens
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