The "elusive DMOAD": Aggrecanase inhibition from laboratory to clinic.
Clin Exp Rheumatol
; 37 Suppl 120(5): 130-134, 2019.
Article
em En
| MEDLINE
| ID: mdl-31621572
ABSTRACT
From the time of their discovery in 1999, the aggrecanases, and ADAMTS-5 in particular, have been heavily investigated as targets for disease-modifying osteoarthritis drug (DMOAD) development. Here, we provide a brief narrative review of the discovery efforts to target these enzymes, and how this led to the current ongoing programmes that hold promise for the future. We discuss a comparison of inhibition of collagen breakdown versus inhibition of aggrecan breakdown. We then summarise existing programmes that target ADAMTS-5, including small molecule inhibitors, monoclonal neutralising antibodies and nanobodies, and gene editing technologies. We also briefly discuss the potential analgesic effects this strategy may offer in addition to its joint-protective effects.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Endopeptidases
/
Pró-Colágeno N-Endopeptidase
/
Proteínas ADAM
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article