Androgen receptor antagonists

A patent review (2008 - 2011)

Michael L. Mohler, Christopher C. Coss, Charles B. Duke, Shivaputra A. Patil, Duane Miller, James T. Dalton

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Introduction: 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. Areas covered: AR antagonists whose patents published between 2008 and 2011 are reviewed. Antagonists are organized based on the screening paradigm reported as discussed above. Expert opinion: 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 improved clinical efficacy, but no clinical proof of concept as of yet.

Original languageEnglish (US)
Pages (from-to)541-565
Number of pages25
JournalExpert Opinion on Therapeutic Patents
Volume22
Issue number5
DOIs
StatePublished - May 1 2012

Fingerprint

Androgen Receptor Antagonists
Castration
Prostatic Neoplasms
Androgen Receptors
Patents
Expert Testimony
Androgens
Down-Regulation
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

Androgen receptor antagonists : A patent review (2008 - 2011). / Mohler, Michael L.; Coss, Christopher C.; Duke, Charles B.; Patil, Shivaputra A.; Miller, Duane; Dalton, James T.

In: Expert Opinion on Therapeutic Patents, Vol. 22, No. 5, 01.05.2012, p. 541-565.

Research output: Contribution to journalReview article

Mohler, Michael L. ; Coss, Christopher C. ; Duke, Charles B. ; Patil, Shivaputra A. ; Miller, Duane ; Dalton, James T. / Androgen receptor antagonists : A patent review (2008 - 2011). In: Expert Opinion on Therapeutic Patents. 2012 ; Vol. 22, No. 5. pp. 541-565.
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