Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.
FEBS Lett
; 591(1): 240-251, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27878989
ABSTRACT
Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors. PDB ID CODES Comp. 2 5IEZ; Comp. 5 5IF4.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína de Sequência 1 de Leucemia de Células Mieloides
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article