Androgen receptor antagonists: a patent review (2008-2011)

Expert Opinion on Therapeutic Patents
Michael L MohlerJames T Dalton

Abstract

Androgen receptor (AR) antagonists are predominantly used as chemical castration to treat prostate cancer (i.e., in conjunction with androgen deprivation therapy (ADT)). Unfortunately, castration-resistant prostate cancer (CRPC) typically develops that is refractory to targeted therapy. Insights into CRPC biology have led to the emergence of a promising clinical candidate MDV3100 (1) and a resurgence in this field. A pipeline of preclinical competitive (C-terminally directed) antagonists was discovered using a variety of innovative screening paradigms. Some inhibit nuclear translocation, selectively downregulate or degrade AR (SARD), antagonize wild-type and escape mutant AR (pan-antagonists) and/or antagonize AR target organs in vivo. Separately, the N-terminal domain has emerged as a promising novel target for noncompetitive antagonists. AR antagonists whose patents published between 2008 and 2011 are reviewed. Antagonists are organized based on the screening paradigm reported as discussed above. Novel mechanisms provide a more informed basis for selecting a competitive antagonist; however, high potency and favorable in vivo properties remain paramount. Noncompetitive antagonists have theoretical advantages suggestive of impr...Continue Reading

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Citations

Mar 1, 2013·Endocrine-related Cancer·Natalie SampsonIris E Eder
Nov 10, 2015·Expert Opinion on Therapeutic Targets·Manuel Luque-Ramírez, Héctor Francisco Escobar-Morreale
Sep 17, 2013·International Journal of Radiation Oncology, Biology, Physics·Harald Bull RagnumHeidi Lyng
Jun 26, 2015·Bioconjugate Chemistry·Valentina RapozziGreta Varchi
Apr 30, 2015·Cancer radiothérapie : journal de la Société française de radiothérapie oncologique·L QueroC Hennequin
May 17, 2019·Expert Opinion on Therapeutic Patents·Shinya Fujii, Hiroyuki Kagechika

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