Understanding the variability of the S1' pocket to improve matrix metalloproteinase inhibitor selectivity profiles.
Drug Discov Today
; 25(1): 38-57, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31513929
ABSTRACT
Matrix metalloproteinases (MMPs) are a family of proteins involved in a range of pathologies. Given that MMP broad-spectrum inhibition is associated with severe adverse effects, selectivity has become a priority in the design of MMP inhibitors, and is often achieved by targeting the variable S1' pocket. However, the specific characteristics of the S1' pocket that determine inhibitor selectivity are often not described and, in many cases, challenging to identify. In this review, we investigate the variability of the S1' pocket across the MMP family, and propose explanations for the selectivity of previously described inhibitors. These analyses provide valuable insights into how to design novel inhibitors selective for a given MMP.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinases da Matriz
/
Inibidores de Metaloproteinases de Matriz
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article