2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε.
Amino Acids
; 43(4): 1577-91, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22331384
ABSTRACT
In this study we identified two heterocyclic compounds (5 and 6) as potent and specific inhibitors of CK1δ (IC(50) = 0.040 and 0.042 µM, respectively). Whereas compound 5 exhibited fivefold higher affinity towards CK1δ than to CK1ε (IC(50) CK1ε = 0.199 µM), compound 6 also inhibited CK1ε (IC(50) = 0.0326 µM) in the same range as CK1δ. Selected compound 5 was screened over 442 kinases identifying 5 as a highly potent and selective inhibitor of CK1δ. X-ray analysis of 5 bound to CK1δ demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biological approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, our optimizations lead to the development of new highly selective CK1δ and ε specific inhibitors with biological activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfopeptídeos
/
Tiazóis
/
Benzimidazóis
/
Caseína Quinase Idelta
/
Caseína Quinase 1 épsilon
/
Inibidores Enzimáticos
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Amino Acids
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha