Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2).
Bioorg Med Chem Lett
; 18(2): 726-31, 2008 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-18060775
ABSTRACT
A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-12). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Inibidores Enzimáticos
/
Inibidores de Histona Desacetilases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos