3.4.24.B12 (1R,2R,3S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2,3-dimethylcyclopropanecarboxylate - 81485 3.4.24.B12 (1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylate - 81471 3.4.24.B12 (1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylic acid - 70416 3.4.24.B12 (1R,2S)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[5-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylic acid - 70417 3.4.24.B12 (1R,2S)-1-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid - 70420 3.4.24.B12 (1R,2S)-1-([[4'-(dimethylamino)biphenyl-4-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid - 70421 3.4.24.B12 (1R,2S)-1-([[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid - 71775 3.4.24.B12 (1R,2S)-1-([[6-(4-chlorophenyl)pyridin-3-yl]sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino)-2-phenylcyclopropanecarboxylic acid - 71776 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-2-ylethyl)amino]-2-phenylcyclopropanecarboxylic acid - 70423 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-3-ylethyl)amino]-2-phenylcyclopropanecarboxylate - 71780 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl](2-pyridin-4-ylethyl)amino]-2-phenylcyclopropanecarboxylic acid - 70424 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl]amino]-2-phenylcyclopropanecarboxylate - 160268 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-1,2,3-triazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate - 71782 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-1,2,4-triazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70425 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-imidazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70426 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(1H-tetrazol-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70427 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2,5-dioxopyrrolidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70428 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxo-1,3-oxazinan-3-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate - 71778 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 71777 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxopiperidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70434 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2-oxopyrrolidin-1-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70435 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(2H-1,2,3-triazol-2-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate - 71781 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(3-methoxy-2-oxopyridin-1(2H)-yl)ethyl]amino]-2-phenylcyclopropanecarboxylate - 71779 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(4H-1,2,4-triazol-4-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70436 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(7H-purin-7-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70437 3.4.24.B12 (1R,2S)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl][2-(9H-purin-9-yl)ethyl]amino]-2-phenylcyclopropanecarboxylic acid - 70438 3.4.24.B12 (1S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2,2-dimethylcyclopropanecarboxylate 0.001 mM, 19.6% inhibition 160272 3.4.24.B12 (1S,2R)-1-([(4'-chlorobiphenyl-4-yl)sulfonyl][2-[4-(methoxycarbonyl)-1H-imidazol-1-yl]ethyl]amino)-2-phenylcyclopropanecarboxylate 0.0003 mM, 18% inhibition 81472 3.4.24.B12 (1S,2R)-1-([[5-(2-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate 0.001 mM, 48% inhibition 160269 3.4.24.B12 (1S,2R)-1-([[5-(3-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate - 81475 3.4.24.B12 (1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-(propan-2-yl)cyclopropanecarboxylate - 81483 3.4.24.B12 (1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-cyclohexylcyclopropanecarboxylate - 81484 3.4.24.B12 (1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methyl-2-phenylcyclopropanecarboxylate - 81481 3.4.24.B12 (1S,2R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate - 81477 3.4.24.B12 (1S,2R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-2-phenylcyclopropanecarboxylate - 81478 3.4.24.B12 (1S,2R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate - 81474 3.4.24.B12 (1S,2R)-1-([[5-(5-chloropyridin-2-yl)thiophen-2-yl]sulfonyl]amino)-2-phenylcyclopropanecarboxylate - 81476 3.4.24.B12 (1S,2R)-1-[[(4'-chlorobiphenyl-4-yl)sulfonyl]amino]-2-phenylcyclopropanecarboxylate - 81473 3.4.24.B12 (1S,2R,3R)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate - 81482 3.4.24.B12 (1S,2R,3R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate - 81479 3.4.24.B12 (1S,2S)-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)-2-methylcyclopropanecarboxylate 0.001 mM, 3.5% inhibition 160270 3.4.24.B12 (1S,2S)-2-benzyl-1-([[5-(4-chloro-1H-pyrazol-1-yl)thiophen-2-yl]sulfonyl]amino)cyclopropanecarboxylate 0.001 mM, 25% inhibition 160271 3.4.24.B12 (1S,2S,3R)-1-([[5-(4-chlorophenyl)thiophen-2-yl]sulfonyl]amino)-2-methyl-3-phenylcyclopropanecarboxylate - 81480 3.4.24.B12 (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 84263 3.4.24.B12 (2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide - 27598 3.4.24.B12 (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 27598 3.4.24.B12 (2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide - 27597 3.4.24.B12 (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 204545 3.4.24.B12 (3R)-N2-(cyclopropylmethyl)-N1-hydroxy-3-(3-hydroxybenzyl)-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-L-aspartamide - 20738 3.4.24.B12 (5E)-2-thioxo-5-([3-[3-(trifluoromethyl)phenoxy]phenyl]methylidene)-1,3-thiazolidin-4-one - 65212 3.4.24.B12 (5E)-3-benzyl-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65213 3.4.24.B12 (5E)-5-([3-methoxy-4-[(4-methoxybenzyl)oxy]phenyl]methylidene)-2-thioxo-1,3-thiazolidin-4-one - 65214 3.4.24.B12 (5E)-5-([4-[(4-chlorobenzyl)oxy]-3-methoxyphenyl]methylidene)-2-thioxo-1,3-thiazolidin-4-one - 65215 3.4.24.B12 (5E)-5-[(3-phenoxyphenyl)methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65216 3.4.24.B12 (5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65217 3.4.24.B12 (5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one - 65218 3.4.24.B12 (5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-ethyl-2-thioxo-1,3-thiazolidin-4-one - 65219 3.4.24.B12 (5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one - 65220 3.4.24.B12 (5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-3-phenyl-2-thioxo-1,3-thiazolidin-4-one - 65221 3.4.24.B12 (5E)-5-[[3,5-bis(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65222 3.4.24.B12 (5E)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65223 3.4.24.B12 (5E)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65224 3.4.24.B12 (5E)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 36861 3.4.24.B12 (5E)-5-[[3-(4-methoxyphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65225 3.4.24.B12 (5E)-5-[[3-(4-methylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65226 3.4.24.B12 (5E)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65227 3.4.24.B12 (5E)-5-[[3-(benzyloxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65228 3.4.24.B12 (5E)-5-[[4-(benzyloxy)-3-methoxyphenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65229 3.4.24.B12 (5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65241 3.4.24.B12 (5Z)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65242 3.4.24.B12 (5Z)-5-[[3-(3,5-dichlorophenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one - 65243 3.4.24.B12 (5Z)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-1-methyl-2-thioxoimidazolidin-4-one - 65244 3.4.24.B12 (5Z)-5-[[3-(4-chlorophenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one - 65245 3.4.24.B12 (5Z)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxo-1,3-thiazolidin-4-one - 65246 3.4.24.B12 (5Z)-5-[[3-(4-tert-butylphenoxy)phenyl]methylidene]-2-thioxoimidazolidin-4-one - 65247 3.4.24.B12 (E)-2-((1H-benzo[d]imidazol-2-yl)methylene)-5-propylthiazolidin-4-one potent small-molecule ADAMTS-5 inhibitor with good permeability 204699 3.4.24.B12 (E)-4-[2-(3,5-dihydroxyphenyl)ethenyl]1,2-benzenediol i.e. piceatannol 15022 3.4.24.B12 (R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 38630 3.4.24.B12 (R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 26090 3.4.24.B12 (R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 26091 3.4.24.B12 (R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 25847 3.4.24.B12 (S)-2-dimethylamino-N-hydroxy-3,3-dimethyl-4-[(4-phenoxyphenyl)-sulfonyl]-butanamide SC81956, potent inhibitor of ADAMTS-5 132647 3.4.24.B12 1-benzyl-4-((4-(4-chlorophenoxy) phenyl)-sulfonyl)-N-hydroxypiperidine-4-carboxamide multi-MMP inhibitor 204820 3.4.24.B12 2-(4-acetylphenoxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]acetamide - 70621 3.4.24.B12 2-(benzyloxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]acetamide - 70626 3.4.24.B12 2-(benzyloxy)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]acetamide - 70627 3.4.24.B12 2-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-methylbutanoic acid - 65385 3.4.24.B12 2-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid - 65386 3.4.24.B12 2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-methylbutanoic acid - 65389 3.4.24.B12 2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid - 65390 3.4.24.B12 2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]acetamide - 70660 3.4.24.B12 2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]acetamide - 70661 3.4.24.B12 2-[4-(acetylamino)phenoxy]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]acetamide - 70662 3.4.24.B12 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 27595 3.4.24.B12 2-[4-(benzyloxy)phenyl]-2,3-dihydro-N-hydroxy-1-oxo-1Hpyrrolo[3,4-c]quinoline-4-carboxamide - 81468 3.4.24.B12 2-[4-(benzyloxy)phenyl]-3-oxoisoindoline-4-carboxylic acid does not inhibit ADAMTS-4 81469 3.4.24.B12 2-[4-(benzyloxy)phenyl]-N-hydroxy-3-oxoisoindoline-4-carboxamide does not inhibit ADAMTS-4 81470 3.4.24.B12 3-[(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid - 65441 3.4.24.B12 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; inhibits the spontaneous aggrecan degradation in IL-1-stimulated bovine cartilage, shows good selectivity over other metalloproteases 205095 3.4.24.B12 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 - 65518 3.4.24.B12 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 - 65519 3.4.24.B12 5-([1,3-diphenyl-5-[(thiophen-2-ylmethyl)sulfanyl]-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65556 3.4.24.B12 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 138621 3.4.24.B12 5-([1-methyl-5-[(4-methylphenyl)sulfanyl]-3-phenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65557 3.4.24.B12 5-([1-phenyl-5-[2-(tetrahydrothiophen-2-yl)ethoxy]-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65558 3.4.24.B12 5-([5-[(2-chlorobenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65559 3.4.24.B12 5-([5-[(4-chlorobenzyl)sulfanyl]-1-methyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65560 3.4.24.B12 5-([5-[(4-chlorobenzyl)sulfanyl]-1-phenyl-3-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65561 3.4.24.B12 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 138622 3.4.24.B12 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 138623 3.4.24.B12 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 - 65562 3.4.24.B12 5-([5-[(furan-2-ylmethyl)sulfanyl]-1,3-diphenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65563 3.4.24.B12 5-([5-[(furan-2-ylmethyl)sulfanyl]-1-methyl-3-phenyl-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65564 3.4.24.B12 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 138624 3.4.24.B12 5-([5-[2-(4-chlorophenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65565 3.4.24.B12 5-([5-[2-(4-fluorophenyl)ethoxy]-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl)-2-thioxo-1,3-thiazolidin-4-one - 65566 3.4.24.B12 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 138625 3.4.24.B12 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 - 65567 3.4.24.B12 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 - 65568 3.4.24.B12 5-[(4-chlorobenzyl)sulfanyl]-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-(2,2,2-trifluoroethyl)-1H-pyrazole-1-carbonitrile - 65579 3.4.24.B12 5-[(furan-2-ylmethyl)sulfanyl]-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-yl)methyl]-3-phenyl-1H-pyrazole-1-carbonitrile - 65581 3.4.24.B12 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 139197 3.4.24.B12 5-[[5-(4-methylpiperazin-1-yl)-1,3-diphenyl-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one - 65584 3.4.24.B12 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 138628 3.4.24.B12 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 138629 3.4.24.B12 5-[[5-(benzylsulfanyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-2-thioxo-1,3-thiazolidin-4-one - 65585 3.4.24.B12 aggrecanase inhibitor BB-16 prevents aggrecan degradation in osteoarthritic cartilage 118278 3.4.24.B12 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 1068 3.4.24.B12 alpha2-Macroglobulin - 1068 3.4.24.B12 batimastat - 4135 3.4.24.B12 BB-16 (2S,5R,6S)-3-Aza-4-oxo-10-oxa-5-hexyl-2-(methylcarboxamido)-10-paracyclophane-6-N-hydroxycarboxamide 13395 3.4.24.B12 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 75515 3.4.24.B12 catechin gallate esters from green tea Camellia sinensis, strong inhibition, independent of Zn2+, reversible 54450 3.4.24.B12 doxycycline dose-dependently inhibits the activity of rhADAMTS4 in vitro 3277 3.4.24.B12 heparin - 227 3.4.24.B12 interleukin-1beta lower mRNA level of aggrecan 2370 3.4.24.B12 marimastat - 3900 3.4.24.B12 minocycline dose-dependently inhibits the activity of rhADAMTS4 in vitro 5378 3.4.24.B12 additional information no inhibition by matrix metalloprotease inhibitor XS309 2 3.4.24.B12 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 2 3.4.24.B12 additional information TIMP-1, TIMP-2 and TIMP-4 do not inhibit ADAMTS-5 2 3.4.24.B12 additional information not inhibited by N-TIMP-1 or TIMP-2; the general proteolytic activitiy of ADAMTS-5 as measured with carboxymethylated transferrin is unaffected by concentrations up to 1 M NaCl 2 3.4.24.B12 additional information substrate specificity of ADAMTS-5 against recombinant aggrecan, aggrecan mutants S377Q and S377T lead to aggrecan cleavage inhibition 2 3.4.24.B12 additional information lower expression level in majority of primary tumors 2 3.4.24.B12 additional information design of ADAMTS-5 inhibitors 2 3.4.24.B12 additional information design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5 2 3.4.24.B12 N-benzyl-N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-D-phenylalanine 30% inhibition at 0.01 mM 146592 3.4.24.B12 N-hydroxy-4-(4-(4-(trifluoromethyl)-phenoxy)phenylsulfonyl)-tetrahydro-2H-pyran-4-carboxamide nanomolar inhibitor of both ADAMTS-5 88019 3.4.24.B12 N-hydroxy-4-([4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonyl)tetrahydro-2H-pyran-4-carboxamide - 65945 3.4.24.B12 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 7044 3.4.24.B12 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 81466 3.4.24.B12 N-[(1R)-1-(dihydroxymethyl)-2-methylpropyl]-4'-{[4-(2-methylpropanoyl)phenoxy]methyl}biphenyl-4-sulfonamide - 139196 3.4.24.B12 N-[(2-chlorophenyl)(8-hydroxy-5-methylquinolin-7-yl)methyl]-2-phenoxyacetamide - 70829 3.4.24.B12 N-[(2-chlorophenyl)(8-hydroxy-5-nitroquinolin-7-yl)methyl]-2-phenoxyacetamide - 70830 3.4.24.B12 N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-D-phenylalanine - 70831 3.4.24.B12 N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-N-(cyclohexylmethyl)-D-phenylalanine 22% inhibition at 0.01 mM 146589 3.4.24.B12 N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-N-(cyclopropylmethyl)-D-phenylalanine 46% inhibition at 0.01 mM 146590 3.4.24.B12 N-[(4'-chlorobiphenyl-4-yl)sulfonyl]-N-methyl-D-phenylalanine - 70832 3.4.24.B12 N-[(5-bromo-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-phenoxyacetamide - 70833 3.4.24.B12 N-[(5-bromo-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide - 70834 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-phenoxyacetamide - 70836 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide - 70835 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide - 70837 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-methyl-N2-phenylglycinamide - 70838 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-cyanophenyl)methyl]-2-phenoxyacetamide - 70839 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-fluorophenyl)methyl]-2-phenoxyacetamide - 70840 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-methylphenyl)methyl]-2-phenoxyacetamide - 70841 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-nitrophenyl)methyl]-2-phenoxyacetamide - 70842 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-2-phenoxyacetamide - 70844 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide - 70843 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide - 70845 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-methyl-N2-phenylglycinamide - 70846 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-(pyridin-3-yloxy)acetamide - 70847 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide - 70848 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide - 70849 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-methyl-N2-phenylglycinamide - 70850 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-chlorophenyl)methyl]-2-phenoxyacetamide - 70851 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(4-methoxyphenoxy)acetamide - 70852 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(4-methylphenoxy)acetamide - 70853 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-(pyridin-3-yloxy)acetamide - 70854 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-phenoxyacetamide - 70856 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methoxyphenyl)methyl]-2-[3-(dimethylamino)phenoxy]acetamide - 70855 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-2-phenoxyacetamide - 70857 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-(4-chloro-3-methylphenyl)glycinamide - 70858 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-(4-cyanophenyl)glycinamide - 70859 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-methyl-N2-phenylglycinamide - 70861 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-[3-(dimethylamino)phenyl]glycinamide - 70860 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-nitrophenyl)methyl]-2-phenoxyacetamide - 70862 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-(4-chlorophenoxy)acetamide - 70863 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-(4-methylphenoxy)acetamide - 70864 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide - 70865 3.4.24.B12 N-[(5-chloro-8-hydroxyquinolin-7-yl)[2-(trifluoromethyl)phenyl]methyl]-2-phenoxyacetamide - 70866 3.4.24.B12 N-[(5-fluoro-8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide - 70867 3.4.24.B12 N-[(8-hydroxy-5-methylquinolin-7-yl)(3-nitrophenyl)methyl]-2-phenoxyacetamide - 70868 3.4.24.B12 N-[(8-hydroxy-5-nitroquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide - 70869 3.4.24.B12 N-[(8-hydroxyquinolin-7-yl)(phenyl)methyl]-2-phenoxyacetamide - 70870 3.4.24.B12 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 205786 3.4.24.B12 N2-(4-acetylphenyl)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]glycinamide - 70883 3.4.24.B12 N2-(4-acetylphenyl)-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]glycinamide - 70884 3.4.24.B12 N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine - 27596 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]-N2-methylglycinamide - 70887 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(2-chlorophenyl)methyl]glycinamide - 70886 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]-N2-methylglycinamide - 70889 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-fluorophenyl)methyl]glycinamide - 70888 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]-N2-methylglycinamide - 70890 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]-N2-methylglycinamide - 70892 3.4.24.B12 N2-benzyl-N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]glycinamide - 70891 3.4.24.B12 N2-[4-(acetylamino)phenyl]-N-[(5-chloro-8-hydroxyquinolin-7-yl)(3-nitrophenyl)methyl]glycinamide - 70885 3.4.24.B12 NaCl the activity is very low at or below 50 mM NaCl or above 500 mM NaCl 42 3.4.24.B12 pyrogallol - 658 3.4.24.B12 tetracycline dose-dependently inhibits the activity of rhADAMTS4 in vitro 2872 3.4.24.B12 TIMP-3 recombinant human inhibitor protein from Escherichia coli, i.e. tissue inhibitor of metalloproteinases, strong inhibitor with regulatory function 1997 3.4.24.B12 TIMP-3 potent inhibitor 1997 3.4.24.B12 TIMP-3 - 1997 3.4.24.B12 tissue inhibitor of matrix metalloproteinases-3 TIMP-3 24110 3.4.24.B12 tissue inhibitor of metalloproteinases-3 - 4708 3.4.24.B12 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 4708 3.4.24.B12 [(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl](phenyl)acetic acid - 65264 3.4.24.B12 [(5E)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid - 65265 3.4.24.B12 [(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl](phenyl)acetic acid - 65267 3.4.24.B12 [(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid - 65268