General Information of the Protein
Protein ID
PT01058
Protein Name
Disintegrin and metalloproteinase domain-containing protein 17
Secondarily
Protein Name
Snake venom-like protease
TNF-alpha convertase
TNF-alpha-converting enzyme
Gene Name
ADAM17
Secondarily
Gene Name
CSVP
TACE
Sequence
MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQSPKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEC
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Protease
>
Metallo protease
>
Metallo protease MAM clan
>
Metallo protease M12B subfamily
Function
Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells.
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Uniprot ID
Primary ID:
P78536

Secondarily ID:
O60226
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Ensembl ID
ENSG00000151694
HGNC ID
HGNC:195
Subcellular Location
Membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000072 , A2780
 Cell Line Info 
Compound ID Compound Name Compound Formula
CP0062139
 Compound Info 
(R)-benzyl 3-(4-(but-2-ynyloxy)phenylsulfonamido)-4-(hydroxyamino)-4-oxobutylcarbamate
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C22H25N3O7S
  2
1
IC50 < 10 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 1436 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0132610
 Compound Info 
(2R)-5-(carbamoylamino)-2-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxypentanamide
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C19H22Br2N4O6S
  2
1
IC50 < 10 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 845 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0073959
 Compound Info 
benzyl N-[(4R)-4-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamate
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C26H27Br2N3O7S
  2
1
IC50 = 349 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 = 10000 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0109071
 Compound Info 
benzyl N-[(3R)-3-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-4-(hydroxyamino)-4-oxobutyl]carbamate
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C25H25Br2N3O7S
  2
1
IC50 = 825 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 > 10000 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
CP0132603
 Compound Info 
2-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxyacetamide
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C15H14Br2N2O5S
  2
1
IC50 = 840 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
2
IC50 > 10000 nM
 Bioactivity Info 
   TI
   LI
   LO
   TS
Cell Line ID: CL000476 , A2774
 Cell Line Info 
Cell Line ID: CL000011 , CHO
 Cell Line Info 
Cell Line ID: CL000752 , PBMC iPSC #1
 Cell Line Info 
Cell Line ID: CL000012 , Sf21
 Cell Line Info 
Cell Line ID: CL000084 , SK-OV-3
 Cell Line Info 
Cell Line ID: CL000040 , THP-1
 Cell Line Info 
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0075340
 Compound Info 
(R)-2-(4-(but-2-ynyloxy)phenylsulfonamido)-4-(1,3-dioxoisoindolin-2-yl)-N-hydroxybutanamide
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C22H21N3O7S
  1
1 IC50 = 0.7 nM
CP0099182
 Compound Info 
1-benzoyl-4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-N-hydroxypiperidine-4-carboxamide
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C24H26N2O6S
  1
1 IC50 = 1 nM
CP0109727
 Compound Info 
4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-N-hydroxypiperidine-4-carboxamide
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C17H22N2O5S
  1
1 IC50 = 1.4 nM
CP0076614
 Compound Info 
(S)-2,2-Dimethyl-4-[4-(3,4,5-trimethoxy-phenoxy)-benzenesulfonyl]-thiomorpholine-3-carboxylic acid hydroxyamide
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C22H28N2O8S2
  1
1 IC50 = 1.5 nM
CP0058694
 Compound Info 
4-({[4-(but-2-yn-1-yloxy)benzene]sulfonyl}methyl)-N-hydroxy-1-(propane-2-sulfonyl)piperidine-4-carboxamide
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C20H28N2O7S2
  1
1 IC50 = 1.5 nM
CP0062139
 Compound Info 
(R)-benzyl 3-(4-(but-2-ynyloxy)phenylsulfonamido)-4-(hydroxyamino)-4-oxobutylcarbamate
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C22H25N3O7S
  1
1 IC50 = 1.6 nM
CP0132610
 Compound Info 
(2R)-5-(carbamoylamino)-2-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxypentanamide
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C19H22Br2N4O6S
  1
1 IC50 = 1.9 nM
CP0069922
 Compound Info 
1-acetyl-4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-N-hydroxypiperidine-4-carboxamide
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C19H24N2O6S
  1
1 IC50 = 2.1 nM
CP0061136
 Compound Info 
(7S,8R,11S)-8-[3-(4-ethoxy-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C29H39N3O6
  1
1 IC50 = 2.7 nM
CP0101306
 Compound Info 
N-hydroxy-3-[methyl-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylamino]-1-(2-methylpropanoyl)azetidine-3-carboxamide
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C26H30N4O6S
  2
1 IC50 = 3 nM
2 IC50 = 4 nM
CP0206165
 Compound Info 
(7S,8R,11S)-8-[3-(4-chloro-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C27H34ClN3O5
  1
1 IC50 = 3.4 nM
CP0081842
 Compound Info 
(S)-N-hydroxy-4-(4-(4-hydroxybut-2-ynyloxy)phenylsulfonyl)-2,2-dimethylthiomorpholine-3-carboxamide
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C17H22N2O6S2
  5
1 IC50 = 4 nM
2 IC50 = 5 nM
3 IC50 = 20 nM
4 IC50 = 158.49 nM
5 IC50 = 440 nM
CP0214161
 Compound Info 
(7S,8R,11S)-8-[3-(3,4-dimethoxy-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C29H39N3O7
  1
1 IC50 = 5.2 nM
CP0109554
 Compound Info 
(7S,8R,11S)-8-(3-naphthalen-1-yl-propyl)-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C31H37N3O5
  1
1 IC50 = 6 nM
CP0109621
 Compound Info 
N-hydroxy-2-methyl-3-[4-(3,4,5-trimethoxyphenoxy)phenyl]sulfonylpropanamide
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C19H23NO8S
  1
1 IC50 = 6.5 nM
CP0068569
 Compound Info 
(7S,8R,11S)-8-[3-(2,5-dimethoxy-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C29H39N3O7
  1
1 IC50 = 6.8 nM
CP0149466
 Compound Info 
N-hydroxy-1-(3-methylbutanoyl)-3-[methyl-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylamino]azetidine-3-carboxamide
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C27H32N4O6S
  2
1 IC50 = 7 nM
2 IC50 = 20 nM
CP0063416
 Compound Info 
(7S,8R,11S)-9-Oxo-8-[3-(3,4,5-trimethoxy-phenyl)-propyl]-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C30H41N3O8
  1
1 IC50 = 7.6 nM
CP0068572
 Compound Info 
(S)-2,2-Dimethyl-4-[4-(pyridin-3-yloxy)-benzenesulfonyl]-thiomorpholine-3-carboxylic acid hydroxyamide
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C18H21N3O5S2
  1
1 IC50 = 7.9 nM
CP0095876
 Compound Info 
(3S)-4-{[4-(but-2-yn-1-yloxy)benzene]sulfonyl}-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide
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C17H22N2O5S2
  3
1 IC50 = 8 nM
2 IC50 = 8.4 nM
3 IC50 = 300 nM
CP0073959
 Compound Info 
benzyl N-[(4R)-4-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamate
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C26H27Br2N3O7S
  1
1 IC50 = 11 nM
CP0068570
 Compound Info 
(7S,8R,11S)-8-[3-(3-isopropyl-5-methyl-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C31H43N3O5
  1
1 IC50 = 12 nM
CP0035501
 Compound Info 
(6S,7S)-methyl 7-(hydroxycarbamoyl)-6-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate
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C22H27N3O5
  1
1 IC50 = 14 nM
CP0094685
 Compound Info 
(7S,8R,11S)-8-[3-(3,5-Bis-trifluoromethyl-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7,11-dicarboxylic acid 7-hydroxyamide 11-methylamide
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C29H33F6N3O5
  1
1 IC50 = 33 nM
CP0646470
 Compound Info 
(R)-N-Hydroxy-2-[(4-methoxy-benzenesulfonyl)-pyridin-3-ylmethyl-amino]-3-methyl-butyramide
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C18H24ClN3O5S
  3
1 IC50 = 40.9 nM
2 IC50 = 160 nM
3 IC50 = 231 nM
CP0077428
 Compound Info 
(7S,8R,11S)-11-benzoyl-8-[3-(3,5-dimethoxy-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7-carboxylic acid hydroxyamide
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C34H40N2O7
  1
1 IC50 = 43 nM
CP0109071
 Compound Info 
benzyl N-[(3R)-3-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-4-(hydroxyamino)-4-oxobutyl]carbamate
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C25H25Br2N3O7S
  1
1 IC50 = 43 nM
CP0077433
 Compound Info 
(7S,8R,11S)-11-benzoyl-9-oxo-8-[3-(3,4,5-trimethoxy-phenyl)-propyl]-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7-carboxylic acid hydroxyamide
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C35H42N2O8
  1
1 IC50 = 55 nM
CP0068568
 Compound Info 
(7S,8R,11S)-11-Benzoyl-8-{3-[3-methoxy-5-(2-methoxy-ethoxy)-phenyl]-propyl}-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7-carboxylic acid hydroxyamide
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C36H44N2O8
  1
1 IC50 = 74 nM
CP0196222
 Compound Info 
(7S,8R,11S)-11-Benzoyl-8-[3-(3,5-dibromo-phenyl)-propyl]-9-oxo-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7-carboxylic acid hydroxyamide
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C32H34Br2N2O5
  1
1 IC50 = 87 nM
CP0102082
 Compound Info 
benzyl N-[(4R)-4-[[4-(4-cyano-2-methylphenyl)piperazin-1-yl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamate
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C25H32N6O6S
  1
1 IC50 = 90 nM
CP0050653
 Compound Info 
(7S,8R,11S)-11-Benzoyl-9-oxo-8-(3-p-tolyl-propyl)-2-oxa-10-aza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-triene-7-carboxylic acid hydroxyamide
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C33H38N2O5
  1
1 IC50 = 96 nM
CP0132603
 Compound Info 
2-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxyacetamide
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C15H14Br2N2O5S
  1
1 IC50 = 105 nM
CP0067207
 Compound Info 
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5-phenylpentanamide
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C21H33N3O4
  1
1 IC50 = 860 nM
CP0181737
 Compound Info 
(4S)-3-[4-(4-cyano-2-methylphenyl)piperazin-1-yl]sulfonyl-N-hydroxy-1,3-thiazolidine-4-carboxamide
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C16H21N5O4S2
  1
1 IC50 = 1500 nM
CP0090766
 Compound Info 
(6S,7S)-N-hydroxy-5-methyl-6-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide
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C20H26F3N5O3
  1
1 IC50 = 2045 nM
CP0178548
 Compound Info 
(3S)-4-{[4-(but-2-yn-1-ylamino)benzene]sulfonyl}-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide
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C17H23N3O4S2
  1
1 IC50 = 3500 nM
CP0162166
 Compound Info 
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-N-hydroxy-1-(2-methylpropanoyl)piperidine-4-carboxamide
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C21H29N3O5S
  1
1 IC50 = 3600 nM
CP0055141
 Compound Info 
(5S)-4-[2-(1-adamantyl)ethyl]-5-[(4-hydroxyphenyl)methyl]-1-[(2R)-1-[(2S)-2-[[(6R)-6-[(4-hydroxyphenyl)methyl]-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl]-3-naphthalen-2-ylpropan-2-yl]piperazine-2,3-dione
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C52H61N5O6
  1
1 IC50 = 4200 nM
CP0071876
 Compound Info 
(5S)-5-benzyl-1-[(2R)-1-cyclohexyl-3-[(2S)-2-[[(6S)-2,3-dioxo-6-propylpiperazin-1-yl]methyl]pyrrolidin-1-yl]propan-2-yl]-4-(2-phenylethyl)piperazine-2,3-dione
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C40H55N5O4
  1
1 IC50 = 4300 nM
CP0172727
 Compound Info 
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-N-hydroxy-1-[(2-methylphenyl)carbonyl]piperidine-4-carboxamide
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C25H29N3O5S
  1
1 IC50 = 4800 nM
CP0144364
 Compound Info 
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-N-hydroxy-1-(2-methylbutanoyl)piperidine-4-carboxamide
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C22H31N3O5S
  1
1 IC50 = 4900 nM
CP0159744
 Compound Info 
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-N-hydroxy-1-(propane-2-sulfonyl)piperidine-4-carboxamide
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C20H29N3O6S2
  1
1 IC50 = 5000 nM
CP0140030
 Compound Info 
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-1-N,1-N-diethyl-4-N-hydroxypiperidine-1,4-dicarboxamide
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C22H32N4O5S
  1
1 IC50 = 6400 nM
CP0140017
 Compound Info 
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-N-hydroxy-1-(pyridin-4-ylmethyl)piperidine-4-carboxamide
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C23H28N4O4S
  1
1 IC50 = 7200 nM
CP0128763
 Compound Info 
BMCL193445 Compound 2d
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C22H30N2O7S
  1
1 IC50 = 14000 nM
CP0140019
 Compound Info 
beta-sulfonyl hydroxamate analogue, 7
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C22H31N3O6S
  1
1 IC50 = 16000 nM
CP0144366
 Compound Info 
beta-sulfonyl hydroxamate analogue, 12
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C22H31N3O7S
  1
1 IC50 = 25000 nM
CP0162165
 Compound Info 
N-hydroxy-4-({[4-(pent-3-yn-2-yloxy)benzene]sulfonyl}methyl)-1-(propane-2-sulfonyl)piperidine-4-carboxamide
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C21H30N2O7S2
  1
1 IC50 = 31000 nM
CP0162899
 Compound Info 
beta-sulfonyl hydroxamate analogue, 11
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C23H33N3O6S
  1
1 IC50 > 50000 nM
CP0235263
 Compound Info 
N-hydroxy-4-[({4-[(2-methylpent-3-yn-2-yl)oxy]benzene}sulfonyl)methyl]-1-(propane-2-sulfonyl)piperidine-4-carboxamide
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C22H32N2O7S2
  1
1 IC50 > 50000 nM
Clinical Information about the Protein
Target 1 ( TNF alpha converting enzyme (ADAM17) )
Target Type Clinical trial Target
Disease 2 Target-related Diseases  2
1 Rheumatoid arthritis [ICD-11: FA20]
2 Chronic obstructive pulmonary disease [ICD-11: CA22]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 Apratastat
 Drug Info 
Phase 2
Rheumatoid arthritis
Discontinued Drug(s) 1 Discontinued Drug  1
1 DPC-333
 Drug Info 
Terminated
Rheumatoid arthritis
Preclinical Drug(s) 1 Preclinical Drug  1
1 GW-3333
 Drug Info 
Preclinical
Chronic obstructive pulmonary disease