Inhibition of Bfl-1 with N-aryl maleimides.
Bioorg Med Chem Lett
; 20(22): 6560-4, 2010 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-20933419
ABSTRACT
High-throughput screening of 66,000 compounds using competitive binding of peptides comprising the BH3 domain to anti-apoptotic Bfl-1 led to the identification of 14 validated 'hits' as inhibitors of Bfl-1. N-Aryl maleimide 1 was among the validated 'hits'. A chemical library encompassing over 280 analogs of 1 was prepared following a two-step synthesis. Structure-activity studies for inhibition of Bfl-1 by analogs of N-aryl maleimide 1 revealed a preference for electron-withdrawing substituents in the N-aryl ring and hydrophilic amines appended to the maleimide core. Inhibitors of Bfl-1 are potential development candidates for anti-cancer therapeutics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-bcl-2
/
Maleimidas
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article