Unexpected binding orientation of bulky-B-ring anti-androgens and implications for future drug targets

Charles B. Duke, Amanda Jones, Casey E. Bohl, James T. Dalton, Duane Miller

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Several new androgen receptor antagonists were synthesized and found to have varying activities across typically antiandrogen resistant mutants (Thr877 → Ala and Trp741 → Leu) and markedly improved potency over previously reported panantagonists. X-ray crystallography of a new anti-androgen in an androgen receptor mutant (Thr877 → Ala) shows that the receptor can accommodate the added bulk presented by phenyl to naphthyl substitution, casting doubt on previous reports of predicted binding orientation and the causes of antagonism in bulky-B-ring antagonists.

Original languageEnglish (US)
Pages (from-to)3973-3976
Number of pages4
JournalJournal of Medicinal Chemistry
Volume54
Issue number11
DOIs
StatePublished - Jun 9 2011

Fingerprint

Androgen Receptor Antagonists
Androgen Antagonists
X Ray Crystallography
Androgen Receptors
Androgens
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Unexpected binding orientation of bulky-B-ring anti-androgens and implications for future drug targets. / Duke, Charles B.; Jones, Amanda; Bohl, Casey E.; Dalton, James T.; Miller, Duane.

In: Journal of Medicinal Chemistry, Vol. 54, No. 11, 09.06.2011, p. 3973-3976.

Research output: Contribution to journalArticle

Duke, Charles B. ; Jones, Amanda ; Bohl, Casey E. ; Dalton, James T. ; Miller, Duane. / Unexpected binding orientation of bulky-B-ring anti-androgens and implications for future drug targets. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 11. pp. 3973-3976.
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