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

Authors
de Mol, Eva; Fenwick, R. Bryn; Phang, Christopher T. W.; Buzón, Victor; Szulc, Elzbieta; de la Fuente, Alex; Escobedo, Albert; García, Jesús; Bertoncini, Carlos Walter; Estébanez Perpiñá, Eva; McEwan, Iain J.; Riera, Antoni; Salvatella, Xavier
Publication Year
2016
Language
English
Format
article
Status
Published version
Description
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.
Fil: de Mol, Eva. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: Fenwick, R. Bryn. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: Phang, Christopher T. W.. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: Buzón, Victor. Universidad de Barcelona; España
Fil: Szulc, Elzbieta. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: de la Fuente, Alex. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: Escobedo, Albert. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: García, Jesús. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: Bertoncini, Carlos Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España
Fil: Estébanez Perpiñá, Eva. Universidad de Barcelona; España
Fil: McEwan, Iain J.. University of Aberdeen; Reino Unido
Fil: Riera, Antoni. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España. Universidad de Barcelona; España
Fil: Salvatella, Xavier. Barcelona Institute of Science and Technology. Institute for Research in Biomedicine; España. Institució Catalana de Recerca i Estudis Avancats; España
Subject
Nuclear Magnetic Resonance
Structure-based drug discovery
Prostate Cancer
Chemical Biology
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Otras Biotecnologías de la Salud
Biotecnología de la Salud
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/50439