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ADAMTS4

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1677

Nomenclature: ADAMTS4

Family: M12: Astacin/Adamalysin

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 837 1q23.3 ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif 4
Mouse - 833 1 79.28 cM Adamts4 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4
Rat - 630 13q24 Adamts4 ADAM metallopeptidase with thrombospondin type 1 motif, 4
Previous and Unofficial Names Click here for help
ADMP-1 | aggrecanase-1 | ADAMTS-4 | ADAMTS-2 | ADAM metallopeptidase with thrombospondin type 1 motif, 4 | ADAM metallopeptidase with thrombospondin type 1 motif | a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif
Database Links Click here for help
Specialist databases
MEROPS M12.221 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.4.24.82

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 15c [PMID: 21536437] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 2
pIC50 8.9 (IC50 1.2x10-9 M) [2]
Immunopharmacology Comments
ADAMTS4 and -5 diminish cartilage integrity in rheumatoid arthritis (RA) by catalysing degradation of aggrecan [3-4].
The activity of ADAMTS4 has been implicated in inducing excessive fibroblast activity and lower respiratory tract tissue damage in viral infection-related acute respiratory distress syndrome (ARDS) [1]. This suggests that inhibition of ADAMTS4 protease activity might be applicable to limit lung damage and improve clinical outcomes following severe respiratory infections.
Immuno Disease Associations
Disease Name:  Rheumatoid arthritis
Disease Synonyms:  no synonynms
Comment:  ADAMTS4 is involved in RA pathogenesis.
Disease X-refs:  Disease Ontology: DOID:7148
OMIM: 180300
References:  3-4
Disease Name:  Osteoarthritis
Disease Synonyms:  no synonynms
Comment:  ADAMTS4 and -5 are major players in development of OA. In human OA ADAMTS4 is induced by IL-1α and TNF-α, two cytokines involved in OA.
Disease X-refs:  Disease Ontology: DOID:8398
References:  5-6

References

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1. Boyd DF, Allen EK, Randolph AG, Guo X-ZJ, Weng Y, Sanders CJ, Bajracharya R, Lee NK, Guy CS, Vogel P et al.. (2020) Exuberant fibroblast activity compromises lung function via ADAMTS. Nature, [Online ahead of print]. DOI: 10.1038/s41586-020-2877-5 [PMID:33116313]

2. De Savi C, Pape A, Sawyer Y, Milne D, Davies C, Cumming JG, Ting A, Lamont S, Smith PD, Tart J et al.. (2011) Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis. Bioorg. Med. Chem. Lett., 21 (11): 3301-6. [PMID:21536437]

3. McInnes IB, Schett G. (2011) The pathogenesis of rheumatoid arthritis. N. Engl. J. Med., 365 (23): 2205-19. [PMID:22150039]

4. Porter S, Clark IM, Kevorkian L, Edwards DR. (2005) The ADAMTS metalloproteinases. Biochem. J., 386 (Pt 1): 15-27. [PMID:15554875]

5. Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW. (2007) Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum., 56 (2): 575-85. [PMID:17265492]

6. Yamanishi Y, Boyle DL, Clark M, Maki RA, Tortorella MD, Arner EC, Firestein GS. (2002) Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J. Immunol., 168 (3): 1405-12. [PMID:11801682]

How to cite this page

M12: Astacin/Adamalysin: ADAMTS4. Last modified on 29/10/2020. Accessed on 24/01/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1677.