Identification of lipid-like salicylic acid-based derivatives as potent and membrane-permeable PTP1B inhibitors.
Bioorg Chem
; 93: 103296, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31585268
Developing protein tyrosine phosphatase-1B (PTP1B) inhibitors is an important strategy to treat type 2 diabetes mellitus (T2DM). Most existing ionic PTP1B inhibitors aren't of clinical useful due to their low cell-permeability, however. Herein, we introduced a series of lipid-like acid-based (salicylic acid) modules to prepare PTP1B inhibitors, and demonstrated a marked improvement of cell-permeability while maintaining excellent PTP1B inhibitory activity (e.g. compound B12D, IC50â¯=â¯0.37⯵M against PTP1B and Pappâ¯=â¯1.5â¯×â¯10-6â¯cm/s). We believe that this strategy can be widely utilized to modify potent lead compounds with low cell-permeability.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Salicílico
/
Inibidores Enzimáticos
/
Proteína Tirosina Fosfatase não Receptora Tipo 1
/
Lipídeos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China