Editing Antiandrogen (section)

====N-Terminal domain antagonists====
[[Peptide antiandrogen|N-Terminal domain AR antagonist]]s are a new type of AR antagonist that, unlike all currently marketed AR antagonists, bind to the [[N-terminal domain]] (NTD) of the AR rather than the [[ligand-binding domain]] (LBD).<ref name="ImamuraSadar2016">{{cite journal | vauthors = Imamura Y, Sadar MD | title = Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic | journal = International Journal of Urology | volume = 23 | issue = 8 | pages = 654–665 | date = August 2016 | pmid = 27302572 | pmc = 6680212 | doi = 10.1111/iju.13137 }}</ref> Whereas conventional AR antagonists bind to the LBD of the AR and [[competitive antagonist|competitively]] displace androgens, thereby preventing them from [[Receptor (biochemistry)#Binding and activation|activating]] the receptor, AR NTD antagonists bind [[covalent bond|covalently]] to the NTD of the AR and prevent [[protein–protein interaction]]s subsequent to activation that are required for [[transcription (biology)|transcriptional activity]].<ref name="ImamuraSadar2016" /> As such, they are [[non-competitive antagonist|non-competitive]] and [[irreversible antagonist]]s of the AR.<ref name="De MolFenwick2016">{{cite journal | vauthors = De Mol E, Fenwick RB, Phang CT, Buzón V, Szulc E, de la Fuente A, Escobedo A, García J, Bertoncini CW, Estébanez-Perpiñá E, McEwan IJ, Riera A, Salvatella X | display-authors = 6 | title = EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor | journal = ACS Chemical Biology | volume = 11 | issue = 9 | pages = 2499–2505 | date = September 2016 | pmid = 27356095 | pmc = 5027137 | doi = 10.1021/acschembio.6b00182 }}</ref> Examples of AR NTD antagonists include [[bisphenol A diglycidyl ether]] (BADGE) and its derivatives [[EPI-001]], [[ralaniten]] (EPI-002), and [[ralaniten acetate]] (EPI-506).<ref name="ImamuraSadar2016" /><ref name="pmid26389532">{{cite journal | vauthors = Martinez-Ariza G, Hulme C | title = Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer | journal = Pharmaceutical Patent Analyst | volume = 4 | issue = 5 | pages = 387–402 | year = 2015 | pmid = 26389532 | doi = 10.4155/ppa.15.20 }}</ref> AR NTD antagonists are under investigation for the potential treatment of prostate cancer, and it is thought that they may have greater [[efficacy]] as antiandrogens relative to conventional AR antagonists.<ref name="ImamuraSadar2016" /> In accordance with this notion, AR NTD antagonists are active against [[splice variant]]s of the AR, which conventional AR antagonists are not, and AR NTD antagonists are immune to [[gain-of-function mutation]]s in the AR LBD that convert AR antagonists into AR agonists and commonly occur in prostate cancer.<ref name="ImamuraSadar2016" />