Structure-guided design of alpha-amino acid-derived Pin1 inhibitors.
Bioorg Med Chem Lett
; 20(2): 586-90, 2010 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-19969456
The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC(50) <100nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptidilprolil Isomerase
/
Inibidores Enzimáticos
/
Aminoácidos
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article