Y06014 is a selective BET inhibitor for the treatment of prostate cancer.
Acta Pharmacol Sin
; 42(12): 2120-2131, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-33654218
ABSTRACT
Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Indóis
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Isoxazóis
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Antineoplásicos
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article