Urea-containing peptide boronic acids as potent proteasome inhibitors.
Eur J Med Chem
; 125: 925-939, 2017 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-27769033
ABSTRACT
A novel class of urea-containing peptide boronic acids as proteasome inhibitors was designed by introducing a urea scaffold to replace an amido bond. Compounds were synthesized and their antitumor activities were evaluated. After two rounds of optimizations, the compound I-14 was found to be a potent proteasome inhibitor. Compared with Bortezomib, I-14 showed higher potency against the chymotrypsin-like activity of human 20S proteasome (IC50 < 1 pM), similar potency against four different cancer cell lines (IC50 < 10 nM), and better pharmacokinetic profile. Furthermore, I-14 significantly inhibited tumor growth in Bel7404 mouse xenograft model. The excellent proteasome inhibition by I-14 was rationalized through docking and molecular dynamics studies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Ácidos Borónicos
/
Inhibidores de Proteasoma
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2017
Tipo del documento:
Article