title: 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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: De Mol
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: R Bryn
authors.initials: RB
authors.lastname: Fenwick
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Christopher T W
authors.initials: CT
authors.lastname: Phang
authors.affiliation: Departament de Bioquímica i Biología Molecular, and Institute of Biomedicine, University of Barcelona (IBUB) , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Buzón
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Szulc
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: de la Fuente
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Escobedo
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Carlos W
authors.initials: CW
authors.lastname: Bertoncini
authors.affiliation: Departament de Bioquímica i Biología Molecular, and Institute of Biomedicine, University of Barcelona (IBUB) , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Estébanez-Perpiñá
authors.affiliation: Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen , IMS Building, Foresterhill, Aberdeen AB25 2ZD, Scotland , United Kingdom.
authors.forename: Iain J
authors.initials: IJ
authors.lastname: McEwan
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.|Departament de Química Orgànica, Universitat de Barcelona , Martí i Franqués 1-11, 08028 Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Riera
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, 08028 Barcelona, Spain.|ICREA, Passeig Lluís Companys 23 , 08010 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Salvatella
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002728:Chlorohydrins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D001559:Benzhydryl Compounds; D002728:Chlorohydrins; C551471:EPI 001; D011944:Receptors, Androgen