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

Eva De Moll, R. Bryn Fenwick, Christopher T.W. Phang, Victor Buzon, Elzbieta Szulc, Alex De La Fuente, Albert Escobedo, Jesus Garcia, Carlos W. Bertoncini, Eva Estebanez-Perpina, Iain J. McEwan, Antoni Riera, Xavier Salvatella

Research output: Contribution to journalArticle

33 Citations (Scopus)
6 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)2499-2505
Number of pages6
JournalACS Chemical Biology
Volume11
Issue number9
Early online date29 Jun 2016
DOIs
Publication statusPublished - 16 Sep 2016

Fingerprint Dive into the research topics of 'EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor'. Together they form a unique fingerprint.

  • Cite this

    Moll, E. D., Fenwick, R. B., Phang, C. T. W., Buzon, V., Szulc, E., De La Fuente, A., Escobedo, A., Garcia, J., Bertoncini, C. W., Estebanez-Perpina, E., McEwan, I. J., Riera, A., & Salvatella, X. (2016). EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor. ACS Chemical Biology, 11(9), 2499-2505. https://doi.org/10.1021/acschembio.6b00182