Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)

J Med Chem. 2010 Apr 8;53(7):2779-96. doi: 10.1021/jm901488g.

Abstract

A structure-activity relationship study was carried out on a series of thiohydantoins and their analogues 14 which led to the discovery of 92 (MDV3100) as the clinical candidate for the treatment of hormone refractory prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Receptor Antagonists*
  • Androgens
  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Male
  • Orchiectomy*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery*
  • Receptors, Androgen / metabolism
  • Structure-Activity Relationship
  • Thiohydantoins / chemical synthesis
  • Thiohydantoins / chemistry*
  • Thiohydantoins / pharmacology*
  • Thiohydantoins / therapeutic use
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Androgen Receptor Antagonists
  • Androgens
  • Receptors, Androgen
  • Thiohydantoins