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EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor.

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.

SUBMITTER: De Mol E 

PROVIDER: S-EPMC5027137 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor.

De Mol Eva E   Fenwick R Bryn RB   Phang Christopher T W CT   Buzón Victor V   Szulc Elzbieta E   de la Fuente Alex A   Escobedo Albert A   García Jesús J   Bertoncini Carlos W CW   Estébanez-Perpiñá Eva E   McEwan Iain J IJ   Riera Antoni A   Salvatella Xavier X  

ACS chemical biology 20160714 9

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 nucle  ...[more]

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