Design, synthesis and biological evaluation of regioisomers of 666-15 as inhibitors of CREB-mediated gene transcription.
Bioorg Med Chem Lett
; 27(4): 994-998, 2017 02 15.
Article
en En
| MEDLINE
| ID: mdl-28073675
ABSTRACT
cAMP-response element binding protein (CREB) is a nuclear transcription factor that has been implicated in the pathogenesis and maintenance of various types of human cancers. Identification of small molecule inhibitors of CREB-mediated gene transcription has been pursued as a novel strategy for developing cancer therapeutics. We recently discovered a potent and cell-permeable CREB inhibitor called 666-15. 666-15 is a bisnaphthamide and has been shown to possess efficacious anti-breast cancer activity without toxicity in vivo. In this study, we designed and synthesized a series of analogs of 666-15 to probe the importance of regiochemistry in naphthalene ring B. Biological evaluations of these analogs demonstrated that the substitution pattern of the alkoxy and carboxamide in naphthalene ring B is very critical for maintaining potent CREB inhibition activity, suggesting that the unique bioactive conformation accessible in 666-15 is critically important.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Anilidas
/
Naftalenos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
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UK
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UNITED KINGDOM