ADAM17 | M12: Astacin/Adamalysin | IUPHAR Guide to IMMUNOPHARMACOLOGY

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ADAM17

Target id: 1662

Nomenclature: ADAM17

Family: M12: Astacin/Adamalysin

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: ON :     ADAM17 has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 824 2p25 ADAM17 ADAM metallopeptidase domain 17
Mouse - 846 12 A1.3 Adam17 a disintegrin and metallopeptidase domain 17
Rat - 827 6q16 Adam17 ADAM metallopeptidase domain 17
Previous and Unofficial Names
CD156B | cSVP | snake venom-like protease | TACE | TNF α convertase | TNF α-converting enzyme | tumor necrosis factor, alpha, converting enzyme
Database Links
Specialist databases
MEROPS M12.217 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of TACE in complex with IK682.
PDB Id:  2fv5
Ligand:  IK-862
Resolution:  2.1Å
Species:  Human
References:  7
Enzyme Reaction
EC Number: 3.4.24.86

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
IK-862 Hs Inhibition 9.3 pKi 3
pKi 9.3 (Ki 5.6x10-10 M) [3]
SL422 Pig Inhibition 7.9 pKi 11
pKi 7.9 (Ki 1.2x10-8 M) [11]
Description: Partially purified enzyme from pancreas.
BMS-561392 Hs Inhibition 8.7 pIC50 2
pIC50 8.7 (IC50 2x10-9 M) [2]
ilomastat Hs Inhibition 8.1 pIC50 8
pIC50 8.1 (IC50 7.5x10-9 M) [8]
Description: Measured in an in vitro assay.
apratastat Hs Inhibition 7.7 pIC50 5
pIC50 7.7 (IC50 2x10-8 M) [5]
GI254023X Hs Inhibition 3.3 pIC50 4
pIC50 3.3 (IC50 5.41x10-4 M) [4]
View species-specific inhibitor tables
Antibody Comments
An anti-ADAM17 (TACE; TNFα converting enzyme) monoclonal antibody, MEDI3622 [9], has shown anti-proliferative activity in tumour models (IC50 ~26 nM vs. H292 cells) [10]. MEDI3622 binds ADAM17 with a Kd of 0.039 nM and inhibits its catalytic activity with a Ki of 3.1 nM [10].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Inflammatory skin and bowel disease, neonatal, 1; NISBD1
Synonyms: Neonatal inflammatory skin and bowel disease [Orphanet: ORPHA294023]
OMIM: 614328
Orphanet: ORPHA294023

References

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1. Chalaris A, Garbers C, Rabe B, Rose-John S, Scheller J. (2011) The soluble Interleukin 6 receptor: generation and role in inflammation and cancer. Eur. J. Cell Biol., 90 (6-7): 484-94. [PMID:21145125]

2. DasGupta S, Murumkar PR, Giridhar R, Yadav MR. (2009) Current perspective of TACE inhibitors: a review. Bioorg. Med. Chem., 17 (2): 444-59. [PMID:19095454]

3. Georgiadis D, Yiotakis A. (2008) Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. Bioorg. Med. Chem., 16 (19): 8781-94. [PMID:18790648]

4. Hoettecke N, Ludwig A, Foro S, Schmidt B. (2010) Improved synthesis of ADAM10 inhibitor GI254023X. Neurodegener Dis, 7 (4): 232-8. [PMID:20197648]

5. Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D et al.. (2006) Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. Bioorg. Med. Chem. Lett., 16 (6): 1605-9. [PMID:16426848]

6. Moss ML, Sklair-Tavron L, Nudelman R. (2008) Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat Clin Pract Rheumatol, 4 (6): 300-9. [PMID:18414459]

7. Niu X, Umland S, Ingram R, Beyer BM, Liu YH, Sun J, Lundell D, Orth P. (2006) IK682, a tight binding inhibitor of TACE. Arch. Biochem. Biophys., 451 (1): 43-50. [PMID:16762314]

8. Oh M, Im I, Lee YJ, Kim YH, Yoon JH, Park HG, Higashiyama S, Kim YC, Park WJ. (2004) Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors. Bioorg. Med. Chem. Lett., 14 (24): 6071-4. [PMID:15546732]

9. Peng L, Cook K, Xu L, Cheng L, Damschroder M, Gao C, Wu H, Dall'Acqua WF. (2016) Molecular basis for the mechanism of action of an anti-TACE antibody. MAbs, 8 (8): 1598-1605. [PMID:27610476]

10. Rios-Doria J, Sabol D, Chesebrough J, Stewart D, Xu L, Tammali R, Cheng L, Du Q, Schifferli K, Rothstein R et al.. (2015) A Monoclonal Antibody to ADAM17 Inhibits Tumor Growth by Inhibiting EGFR and Non-EGFR-Mediated Pathways. Mol. Cancer Ther., 14 (7): 1637-49. [PMID:25948294]

11. Xue CB, Voss ME, Nelson DJ, Duan JJ, Cherney RJ, Jacobson IC, He X, Roderick J, Chen L, Corbett RL et al.. (2001) Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo. J. Med. Chem., 44 (16): 2636-60. [PMID:11472217]

How to cite this page

M12: Astacin/Adamalysin: ADAM17. Last modified on 06/04/2018. Accessed on 19/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1662.