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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 930 | 21q21.3 | ADAMTS5 | ADAM metallopeptidase with thrombospondin type 1 motif 5 | |
| Mouse | - | 930 | 16 48.34 cM | Adamts5 | ADAM metallopeptidase with thrombospondin type 1 motif 5 | |
| Rat | - | 928 | 11q11 | Adamts5 | ADAM metallopeptidase with thrombospondin type 1 motif, 5 | |
| Previous and Unofficial Names |
| aggrecanase-2 | ADAMTS11 | ADMP-2 | ADAM metallopeptidase with thrombospondin type 1 motif | a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif |
| Database Links |
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| Specialist databases | |
| MEROPS | M12.225 (Hs) |
| Other databases | |
| Alphafold | Q9UNA0 (Hs), Q9R001 (Mm) |
| BRENDA | 3.4.24.- |
| CATH/Gene3D | 2.20.100.10, 3.40.390.10 |
| ChEMBL Target | CHEMBL2285 (Hs), CHEMBL4879523 (Mm) |
| Ensembl Gene | ENSG00000154736 (Hs), ENSMUSG00000022894 (Mm), ENSRNOG00000057794 (Rn) |
| Entrez Gene | 11096 (Hs), 23794 (Mm), 304135 (Rn) |
| Human Protein Atlas | ENSG00000154736 (Hs) |
| KEGG Enzyme | 3.4.24.- |
| KEGG Gene | hsa:11096 (Hs), mmu:23794 (Mm), rno:304135 (Rn) |
| OMIM | 605007 (Hs) |
| Pharos | Q9UNA0 (Hs) |
| RefSeq Nucleotide | NM_007038 (Hs), NM_011782 (Mm), NM_198761 (Rn) |
| RefSeq Protein | NP_008969 (Hs), NP_035912 (Mm), NP_942056 (Rn) |
| UniProtKB | Q9UNA0 (Hs), Q9R001 (Mm) |
| Wikipedia | ADAMTS5 (Hs) |
| Selected 3D Structures |
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| Enzyme Reaction |
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Disease Associations | ||||||||||
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| General Comments |
| ADAMTS4 and -5 diminish cartilage integrity in rheumatoid arthritis (RA), via their participation in aggrecan degradation [5-6]. ADAMTS5 is a validated drug target for osteoarthritis (OA), with experimental inhibitors attenuating joint damage in models of OA. Galapagos NV have an active ADAMTS5 programme, with their lead agent GLPG1972/S201086 a small molecule ADAMTS5 inhibitor [8], licensed to Servier in mid-2017) having completed Phase 2 clinical trial in patients with knee OA (see NCT03595618). Unpublished data released in October 2020, indicated that GLPG1972 failed to improve outcomes in these patients. GSK's humanized anti-ADAMTS5 monoclonal antibody, GSK2394002 [4] also inhibits ADAMTS5 catalytic activity (Ki 0.08 nM), and was proposed as a potential disease modifying therapeutic for OA, but as of August 2020 it does not appear to have progressed beyond preclinical evaluation. |
1. Brebion F, Gosmini R, Deprez P, Varin M, Peixoto C, Alvey L, Jary H, Bienvenu N, Triballeau N, Blanque R et al.. (2021) Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis. J Med Chem, 64 (6): 2937-2952. [PMID:33719441]
2. Chiusaroli R, Visentini M, Galimberti C, Casseler C, Mennuni L, Covaceuszach S, Lanza M, Ugolini G, Caselli G, Rovati LC et al.. (2013) Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis. Osteoarthr Cartil, 21 (11): 1807-10. [PMID:23954517]
3. 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]
4. Larkin J, Lohr TA, Elefante L, Shearin J, Matico R, Su JL, Xue Y, Liu F, Genell C, Miller RE et al.. (2015) Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification. Osteoarthr Cartil, 23 (8): 1254-66. [PMID:25800415]
5. McInnes IB, Schett G. (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med, 365 (23): 2205-19. [PMID:22150039]
6. Porter S, Clark IM, Kevorkian L, Edwards DR. (2005) The ADAMTS metalloproteinases. Biochem J, 386 (Pt 1): 15-27. [PMID:15554875]
7. 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]
8. van der Aar EM, Desrivot J, Fagard L, Amantini D, Larsson S, Struglics A, Lohmander S, Vanhoutte F, Dupont S. Abstract 584: ADAMTS-5 inhibitor GLPG1972, a potential new treatment in osteoarthritis, shows favorable safety, pharmacokinetics and pharmacodynamics in healthy subjects. Accessed on 19/10/2020. Modified on 19/10/2020. oarsijournal.com, https://www.oarsijournal.com/article/S1063-4584(18)30723-4/abstract. DOI: 10.1016/j.joca.2018.02.623
M12: Astacin/Adamalysin: ADAMTS5. Last modified on 26/06/2023. Accessed on 17/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1678.
