EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor.
ACS Chem Biol
; 11(9): 2499-505, 2016 09 16.
Article
em En
| MEDLINE
| ID: mdl-27356095
ABSTRACT
Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer. Our results can contribute to the development of more potent and less toxic novel androgen receptor antagonists for treating this disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Compostos Benzidrílicos
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Orquiectomia
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Receptores Androgênicos
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Cloridrinas
Limite:
Humans
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Male
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Espanha