title: Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer.
abstract: Prostate cancer (PC) is the second most frequent cause of male cancer death in the USA. As such, the androgen receptor (AR) plays a crucial role in PC, making AR the major therapeutic target for PC. Current antiandrogen chemotherapy prevents androgen binding to the ligand-binding pocket (LBP) of AR. However, PC frequently recurs despite treatment and it progresses to castration-resistant prostate cancer. Behind this regression is renewed AR signaling initiated via mutations in the LBP. Hence, there is a critical need to improve the therapeutic options to regulate AR activity in sites other than the LBP. Herein, recently disclosed (2010-2015) allosteric AR inhibitors are summarized and a perspective on the potential pharmaceutical intervention at these sites is provided.
authors.affiliation: Department of Pharmacology & Toxicology, The University of Arizona, Biological Sciences West Room #351, 1041 E Lowell St, Tucson, AZ 85721, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martinez-Ariza
authors.affiliation: Department of Pharmacology & Toxicology, The University of Arizona, Biological Sciences West Room #351, 1041 E Lowell St, Tucson, AZ 85721, USA.|Department of Chemistry & Biochemistry, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hulme
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism
chemical_list: C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D008024:Ligands; D011944:Receptors, Androgen