SAR optimization studies on modified salicylamides as a potential treatment for acute myeloid leukemia through inhibition of the CREB pathway.
Bioorg Med Chem Lett
; 29(16): 2307-2315, 2019 08 15.
Article
em En
| MEDLINE
| ID: mdl-31253529
ABSTRACT
Disruption of cyclic adenosine monophosphate response element binding protein (CREB) provides a potential new strategy to address acute leukemia, a disease associated with poor prognosis, and for which conventional treatment options often carry a significant risk of morbidity and mortality. We describe the structure-activity relationships (SAR) for a series of XX-650-23 derived from naphthol AS-E phosphate that disrupts binding and activation of CREB by the CREB-binding protein (CBP). Through the development of this series, we identified several salicylamides that are potent inhibitors of acute leukemia cell viability through inhibition of CREB-CBP interaction. Among them, a biphenyl salicylamide, compound 71, was identified as a potent inhibitor of CREB-CBP interaction with improved physicochemical properties relative to previously described derivatives of naphthol AS-E phosphate.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Salicilamidas
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Inibidores Enzimáticos
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Proteína de Ligação a CREB
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article