3.4.24.82 (2R)-2-(biphenyl-4-ylsulfonyl)-3-(1H-indol-2-yl)propanoic acid IC50: 0.0028 mM 59994 3.4.24.82 (2R)-2-(biphenyl-4-ylsulfonyl)-3-phenylpropanoic acid IC50: 0.0043 mM 59993 3.4.24.82 (2R)-2-(biphenyl-4-ylsulfonyl)pentanedioic acid IC50: 0.0011 mM 59992 3.4.24.82 (2R)-2-(biphenyl-4-ylsulfonyl)propanoic acid IC50: 0.0055 mM 59991 3.4.24.82 (2R)-2-([[3'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid - 87119 3.4.24.82 (2R)-2-([[3'-(aminomethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid - 87120 3.4.24.82 (2R)-2-([[3'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid - 87117 3.4.24.82 (2R)-2-([[4'-(acetylamino)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid - 87114 3.4.24.82 (2R)-2-([[4'-(carbamoyloxy)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid - 41997 3.4.24.82 (2R)-2-([[4'-(hydroxymethyl)biphenyl-4-yl]sulfonyl]amino)-3-methylbutanoic acid - 87115 3.4.24.82 (2R)-2-[(biphenyl-4-ylsulfonyl)amino]-3-methylbutanoic acid - 87108 3.4.24.82 (2R)-2-[[(3'-carbamoylbiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid - 87118 3.4.24.82 (2R)-2-[[(3'-cyanobiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid - 87122 3.4.24.82 (2R)-2-[[(3'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid - 87116 3.4.24.82 (2R)-2-[[(4'-hydroxybiphenyl-4-yl)sulfonyl]amino]-3-methylbutanoic acid - 87098 3.4.24.82 (2R)-3-methyl-2-[([4'-[(methylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)amino]butanoic acid - 88015 3.4.24.82 (2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide - 27598 3.4.24.82 (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-optimizing its interaction pattern step-by-step, following the loop motion. The conformational flexibility observed for the S1' loop of ADAMTS4 and ADAMTS5 seems to be correlated to the motion of the TS-domain 27598 3.4.24.82 (2R,5R)-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide - 27597 3.4.24.82 (2R,5R)-1-([4-[(5-fluoro-2-methylbenzyl)oxy]phenyl]sulfonyl)-N,5-dihydroxypiperidine-2-carboxamide IC50: 145 nM 59982 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2,4-dichlorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 2.1 nM 60044 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 16 nM 60037 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-chloro-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 0.5 nM 60043 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-ethylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 67 nM 60039 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-isopropylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide 78% inhibition of enzyme activity at 500 nM 131954 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-3-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 3.9 nM 60040 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-4-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 2.7 nM 60041 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-methyl-5-fluorobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 40 nM 60042 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(2-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 38 nM 60035 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(3-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide 57% inhibition of enzyme activity at 500 nM 131953 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(3-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 100 nM 60036 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(3-methylisothiazol-4-yl)methoxy]phenyl]sulfonyl)piperidine-2-carboxamide 76% inhibition of enzyme activity at 500 nM 131955 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(4-bromobenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide IC50: 100 nM 60038 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(4-methylbenzyl)oxy]phenyl]sulfonyl)piperidine-2-carboxamide 19% inhibition of enzyme activity at 500 nM 131952 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-([4-[(4-methylisothiazol-5-yl)methoxy]phenyl]sulfonyl)piperidine-2-carboxamide 55% inhibition of enzyme activity at 500 nM 131956 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-[[4-(2-chloropyridin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide IC50: 18 nM 60047 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-[[4-(2-methylpyridin-3-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide IC50: 91 nM 60048 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-[[4-(isoquinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide IC50: 100 nM 60045 3.4.24.82 (2R,5R)-N,5-dihydroxy-1-[[4-(quinolin-4-ylmethoxy)phenyl]sulfonyl]piperidine-2-carboxamide IC50: 15 nM 60046 3.4.24.82 (2S,3R)-2-[(cyclopropylmethyl)amino]-N1-hydroxy-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-methylbutanediamide the reduced pattern of H-bond interactions is suitable for the flexible environment of ADAMTS4 and ADAMTS5 since it enables the inhibitor to re-optimizing its interaction pattern step-by-step, following the loop motion. The conformational flexibility observed for the S1' loop of ADAMTS4 and ADAMTS5 seems to be correlated to the motion of the TS-domain 204545 3.4.24.82 (3R)-N2-(cyclopropylmethyl)-N1-hydroxy-3-(3-hydroxybenzyl)-N4-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-L-aspartamide - 20738 3.4.24.82 (E)-4-[2-(3,5-dihydroxyphenyl)ethenyl]1,2-benzenediol i.e. piceatannol 15022 3.4.24.82 (R)-2-(3-fluoro-4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 71188 3.4.24.82 (R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72836 3.4.24.82 (R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72837 3.4.24.82 (R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72838 3.4.24.82 (R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 71191 3.4.24.82 (R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72839 3.4.24.82 (R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72840 3.4.24.82 (R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72841 3.4.24.82 (R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 38630 3.4.24.82 (R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 26090 3.4.24.82 (R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 71187 3.4.24.82 (R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72842 3.4.24.82 (R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72843 3.4.24.82 (R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 26091 3.4.24.82 (R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid - 72844 3.4.24.82 (R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72845 3.4.24.82 (R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72846 3.4.24.82 (R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 71189 3.4.24.82 (R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72847 3.4.24.82 (R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72848 3.4.24.82 (R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72849 3.4.24.82 (R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72850 3.4.24.82 (R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72851 3.4.24.82 (R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid - 71192 3.4.24.82 (R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid - 72852 3.4.24.82 (R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 25847 3.4.24.82 (R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid - 72853 3.4.24.82 2-deoxyfluoroglucose 0.01 mM 132643 3.4.24.82 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 3.4.24.82 2-[4-(benzyloxy)phenyl]-2,3-dihydro-N-hydroxy-1-oxo-1H-pyrrolo[3,4-c]quinoline-4-carboxamide - 81467 3.4.24.82 3-[(biphenyl-4-ylsulfonyl)amino]-4-methylpentanoic acid IC50: 0.1 mM 59990 3.4.24.82 3-[[(4'-[[(1R)-1-carboxy-2-methylpropyl]sulfamoyl]biphenyl-4-yl)oxy]methyl]benzoic acid - 87222 3.4.24.82 acetyl-DVQEFRGVTAVIRNH2 - 139182 3.4.24.82 acetyl-HNEFRQRETYMVF-NH2 - 139183 3.4.24.82 actinonin 0.01 mg/ml, 61% inhibition 564 3.4.24.82 AG3340 0.00066 mM, 50% inhibition, hydroxamate-based matrix metalloproteinase inhibitor 13391 3.4.24.82 AG3340 non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 120 nM 13391 3.4.24.82 AG490 0.01 mM 10062 3.4.24.82 alpha2-Macroglobulin - 1068 3.4.24.82 antibody 237-53 antibody 237-53 almost completely blocks the activity of the enzyme in a molar ratio of 1:5 (enzyme:antibody) 240078 3.4.24.82 batimastat - 4135 3.4.24.82 BB-16 0.000548 mM, 50% inhibition 13395 3.4.24.82 BB-16 0.000159 mM, 50% inhibition 13395 3.4.24.82 BB-16 0.1 mM, complete inhibition of aggrecanase 1 and 2 13395 3.4.24.82 BB-16 peptidomimetric hydroxamate, synthetic inhibitor originally targeted for matrix metalloproteinases, IC50: 150 nM 13395 3.4.24.82 BB94 0.000524 mM, 85% inhibition, hydroxamate-based matrix metalloproteinase inhibitor 7513 3.4.24.82 C-terminal 40-kDa fibronectin fragment wild type enzyme IC50: 170 nM, complete inhibition at 750 nM 60950 3.4.24.82 calcium pentosan polysulfate no impact on gene expression, but directly inhibit the aggrecanase activity 75515 3.4.24.82 chondroitin 6-sulfate - 1675 3.4.24.82 chondroitin sulfate - 2476 3.4.24.82 CT-1746 0.000048 mM, 50% inhibition, hydroxamate-based matrix metalloproteinase inhibitor 113228 3.4.24.82 D-mannosamine 1.5 mM 5145 3.4.24.82 dermatan sulfate - 907 3.4.24.82 doxycycline dose-dependently inhibits the activity of rhADAMTS4 in vitro 3277 3.4.24.82 DPC non-peptidomimetric hydroxamate matrix metalloproteinase inhibitor, IC50: 10 nM 60947 3.4.24.82 EDTA 5 mM, complete inhibition 21 3.4.24.82 EDTA 1 mM, complete inhibition of aggrecanase 1 and 2 21 3.4.24.82 EGTA 5 mM, complete inhibition 173 3.4.24.82 enoxaparin - 8512 3.4.24.82 fibronectin IC50: 110 nM 3113 3.4.24.82 fibronectin wild type enzyme IC50: 110 nM, complete inhibition at 500 nM 3113 3.4.24.82 GGWGPWGPWGD peptide representing the N-terminal region of the aggrecane TPS-1 motif containign the GAG binding motif, 0.017 mM, 50% inhibition 113550 3.4.24.82 GGWGPWGPWGDCSRTCGGG peptide containing both the GAG and CD36 binding motifs of aggrecan, 0.003 mM, 50% inhibition 51674 3.4.24.82 glycosaminoglycan - 15773 3.4.24.82 heparan sulfate - 1073 3.4.24.82 heparin - 227 3.4.24.82 heparin 0.1 mg/ml, selective inhibition of full-length ADAMTS-4 227 3.4.24.82 hyaluronan hyaluronan 800 kDA and 2700 kDa decreased IL1alpha-induced expression of aggrecanase-1 decreased 1948 3.4.24.82 interleukin-1beta lower mRNA level of aggrecan 2370 3.4.24.82 Janus kinase 2 inhibitor 10 g/ml 139184 3.4.24.82 Janus kinase 3 inhibitor 30 g/ml 139185 3.4.24.82 KB-R7785 - 22117 3.4.24.82 Keratan sulfate - 3642 3.4.24.82 LY294002 0.01 mM, reduces ADAMTS-4 expression 770 3.4.24.82 marimastat IC50: 210 nM 3900 3.4.24.82 marimastat - 3900 3.4.24.82 minocycline dose-dependently inhibits the activity of rhADAMTS4 in vitro 5378 3.4.24.82 additional information no inhibitory effect of alpha1-antitrypsin 2 3.4.24.82 additional information ADAMTS-4 is not inhibited by 125 nM or less tissue inhibitor of metalloproteinase-1 2 3.4.24.82 additional information no inhibition by tissue inhibitor of metalloproteinases 1 or tissue inhibitor of metalloproteinases 2 at 100 nM 2 3.4.24.82 additional information no inhibition of ADAMTS4 deletion mutants including DELTASp (DELTAArg693-Lys837, lacking the spacer domain) 2 3.4.24.82 additional information substrate specificity of ADAMTS-4 against recombinant aggrecan, aggrecan mutants V356A-V361A-E362D, V361Q-E362K, D360H-V361Q-E362K, S377Q lead to aggrecan cleavage inhibition 2 3.4.24.82 additional information lower expression level in majority of primary tumors 2 3.4.24.82 additional information down-regulation of IL-1beta-induced ADAMTS-4 activation by Ras knockdown or inhibition of reactive oxygen species by antioxidants along with ablation of MyD88, IRAK1, or TRAF6; inducing effect of IL-1beta partially blocked by knockdown of adaptor proteins MyD88, IRAK1 or TRAF6 2 3.4.24.82 additional information design of ADAMTS-4 inhibitors. No inhibition observed with the ADAMTS-5 inhibitors: 2-[4-(benzyloxy)phenyl]-3-oxoisoindoline-4-carboxylic acid or 2-[4-(benzyloxy)phenyl]-N-hydroxy-3-oxoisoindoline-4-carboxamide 2 3.4.24.82 additional information design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5 2 3.4.24.82 N-(biphenyl-3-ylsulfonyl)-D-valine IC50: 0.1 mM 59984 3.4.24.82 N-(biphenyl-4-ylsulfonyl)-D-valine IC50: 0.003 mM 59983 3.4.24.82 N-(biphenyl-4-ylsulfonyl)-L-valine IC50: 0.1 mM 59989 3.4.24.82 N-(biphenyl-4-ylsulfonyl)-N-(pyridin-3-ylmethyl)-D-valine IC50: 0.012 mM 60949 3.4.24.82 N-(biphenyl-4-ylsulfonyl)-N-methyl-D-valine IC50: 0.0016 mM 59995 3.4.24.82 N-([3'-[(acetylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine - 87121 3.4.24.82 N-([4'-[(1-benzofuran-2-ylcarbonyl)amino]biphenyl-4-yl]sulfonyl)-D-valine IC50: 0.0075 mM 59998 3.4.24.82 N-([4'-[(1-benzofuran-2-ylcarbonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine IC50: 0.00035 mM 59996 3.4.24.82 N-([4'-[(2-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87214 3.4.24.82 N-([4'-[(2-methylpyridin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine - 87138 3.4.24.82 N-([4'-[(2-methylquinolin-4-yl)methoxy]biphenyl-4-yl]sulfonyl)-D-valine - 87103 3.4.24.82 N-([4'-[(3-bromobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87225 3.4.24.82 N-([4'-[(3-chlorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87224 3.4.24.82 N-([4'-[(3-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87215 3.4.24.82 N-([4'-[(3-fluorobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87223 3.4.24.82 N-([4'-[(3-hydroxybenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87226 3.4.24.82 N-([4'-[(3-nitrobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87210 3.4.24.82 N-([4'-[(4-cyanobenzyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87217 3.4.24.82 N-([4'-[(benzoylamino)methyl]biphenyl-4-yl]sulfonyl)-D-valine - 87093 3.4.24.82 N-([4'-[(benzylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87097 3.4.24.82 N-([4'-[(furan-2-yloxy)carbonyl]biphenyl-4-yl]sulfonyl)-D-valine IC50: 0.0116 mM 60003 3.4.24.82 N-([4'-[(phenylcarbamoyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87107 3.4.24.82 N-([4'-[(phenylsulfonyl)oxy]biphenyl-4-yl]sulfonyl)-D-valine - 87091 3.4.24.82 N-([4'-[(Z)-2-(1-benzofuran-2-yl)ethenyl]biphenyl-4-yl]sulfonyl)-D-valine IC50: 0.0004 mM 60001 3.4.24.82 N-([4'-[2-(1-benzofuran-2-yl)-2-oxoethyl]biphenyl-4-yl]sulfonyl)-D-valine IC50: 0.0038 mM 60000 3.4.24.82 N-terminal domain of tissue inhibitor of metalloproteinases-3 all isoforms of ADAMTS-4 are effectively inhibited. Inhibited more strongly by N-terminal domain of tissue inhibitor of metalloproteinases-3 than by full-length tissue inhibitor of metalloproteinases-3 7044 3.4.24.82 N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3 N-terminal mutants of N-TIMP-3 (tissue inhibitor of metalloproteinases 3) that have lost their matrix metalloproteinase P-inhibitory activities (N-TIMP-3(T2G)and [-1A]N-TIMP-3), retain their ability to inhibit ADAMTS-4 and ADAMTS-5. The [-2A]N-TIMP-3 mutant also retains strong affinity with ADAMTS-5, but has a lower affinity for ADAMTS-4 and ADAM17 81466 3.4.24.82 N-[(2'-aminobiphenyl-4-yl)sulfonyl]-D-valine IC50: 0.05 mM 59986 3.4.24.82 N-[(2'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine IC50: 0.02 mM 59987 3.4.24.82 N-[(2-aminobiphenyl-4-yl)sulfonyl]-D-valine IC50: 0.03 mM 59985 3.4.24.82 N-[(3'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine IC50: 0.009 mM 59988 3.4.24.82 N-[(4'-hydroxybiphenyl-4-yl)sulfonyl]-D-valine IC50: 0.0046 mM 60948 3.4.24.82 N-[(4'-phenoxybiphenyl-4-yl)sulfonyl]-D-valine - 87094 3.4.24.82 N-[(4'-[1-[3-(trifluoromethyl)phenyl]ethoxy]biphenyl-4-yl)sulfonyl]-D-valine - 87219 3.4.24.82 N-[(4'-[[(3-methyl-1-benzofuran-2-yl)carbonyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine IC50: 0.000086 mM 59997 3.4.24.82 N-[(4'-[[(3-methyl-1-benzofuran-2-yl)oxy]methyl]biphenyl-4-yl)sulfonyl]-D-valine IC50: 0.0007 mM 60002 3.4.24.82 N-[(4'-[[2-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine - 87213 3.4.24.82 N-[(4'-[[2-(trifluoromethyl)pyridin-4-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine - 87211 3.4.24.82 N-[(4'-[[3-(methoxycarbonyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine - 87221 3.4.24.82 N-[(4'-[[3-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine - 87216 3.4.24.82 N-[(4'-[[4-(trifluoromethyl)benzyl]oxy]biphenyl-4-yl)sulfonyl]-D-valine - 87229 3.4.24.82 N-[(4'-[[6-(trifluoromethyl)pyridin-2-yl]methoxy]biphenyl-4-yl)sulfonyl]-D-valine - 87212 3.4.24.82 N-[(4'-[[acetyl(methyl)amino]methyl]biphenyl-4-yl)sulfonyl]-D-valine - 87092 3.4.24.82 N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-5-(trifluoromethyl)-1-benzofuran-2-carboxamide - 239036 3.4.24.82 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 3.4.24.82 N-[[4'-(1-benzofuran-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine IC50: 0.0014 mM 59999 3.4.24.82 N-[[4'-(benzyloxy)biphenyl-4-yl]sulfonyl]-D-valine - 87095 3.4.24.82 N-[[4'-(cyclohexylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87099 3.4.24.82 N-[[4'-(naphthalen-1-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87100 3.4.24.82 N-[[4'-(naphthalen-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87101 3.4.24.82 N-[[4'-(pyridin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87152 3.4.24.82 N-[[4'-(pyridin-3-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87105 3.4.24.82 N-[[4'-(pyridin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87076 3.4.24.82 N-[[4'-(quinolin-2-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87104 3.4.24.82 N-[[4'-(quinolin-4-ylmethoxy)biphenyl-4-yl]sulfonyl]-D-valine - 87102 3.4.24.82 N2-(biphenyl-4-ylcarbonyl)-N-(2-phenylpropan-2-yl)-L-alpha-glutamine - 27596 3.4.24.82 NL-71-101 0.02 mM, reduces ADAMTS-4 expression 139186 3.4.24.82 o-phenanthroline 1 mM, complete inhibition of aggrecanase 1 and 2 239 3.4.24.82 parthenolide 0.005 mM, reduces ADAMTS-4 expression 17797 3.4.24.82 PD98059 inhibition of MAP kinase signaling pathway result in inhibition of neurite outgrowth induced by ADAMTS4 3036 3.4.24.82 phosphatidylinositol 3-kinase reduces ADAMTS-4 expression 32711 3.4.24.82 pyrogallol - 658 3.4.24.82 QEYKAHHSYKLMS - 66632 3.4.24.82 SC81956 demonstrates noncompetitive inhibition kinetics 37042 3.4.24.82 SC81956 - 37042 3.4.24.82 SE206 0.000137 mM, 50% inhibition 16956 3.4.24.82 SE206 0.000076 mM, 50% inhibition 16956 3.4.24.82 SE206 0.1 mM, complete inhibition of aggrecanase 1 and 2 16956 3.4.24.82 SE206 macrocyclic derivate of BB-16, IC50: 76 nM 16956 3.4.24.82 tetracycline dose-dependently inhibits the activity of rhADAMTS4 in vitro 2872 3.4.24.82 TIMP-3 - 1997 3.4.24.82 TIMP3 - 75516 3.4.24.82 tinzaparin - 17553 3.4.24.82 tissue inhibitor of matrix metalloproteinases-3 TIMP-3 24110 3.4.24.82 Tissue inhibitor of metalloproteinase-1 150 nM or 270 nM 5659 3.4.24.82 tissue inhibitor of metalloproteinases 3 - 35846 3.4.24.82 tissue inhibitor of metalloproteinases 3 20 nM, complete inhibition 35846 3.4.24.82 tissue inhibitor of metalloproteinases-3 TIMP-3 4708 3.4.24.82 tissue inhibitor of metalloproteinases-3 all isoforms of ADAMTS-4 are effectively inhibited. Inhibited more strongly by N-terminal domain of tissue inhibitor of metalloproteinases-3 than by full-length tissue inhibitor of metalloproteinases-3 4708 3.4.24.82 Tripterygium wilfordii Hook F extract - 132642 3.4.24.82 triptolide 600 nM, PG490 18067 3.4.24.82 U0126 inhibition of MAP kinase signaling pathway result in inhibition of neurite outgrowth induced by ADAMTS4 2692 3.4.24.82 XS309 0.002185 mM, 50% inhibition 114543