Cheminformatics Driven Development of Novel Therapies for Drug Resistant Prostate Cancer

Mol Inform. 2018 Sep;37(9-10):e1800043. doi: 10.1002/minf.201800043. Epub 2018 May 7.

Abstract

Androgen receptor (AR) is a master regulator of prostate cancer (PCa), and therefore is a pivotal drug target for the treatment of PCa including its castration-resistance form (CRPC). The development of acquired resistance is a major challenge in the use of the current antiandrogens. The recent advancements in inhibiting AR activity with small molecules specifically designed to target areas distinct from the receptor's androgen binding site are carefully discussed. Our new classes of AR inhibitors of AF2 and BF3 functional sites and DBD domains designed using cheminformatics techniques are promising to circumvent various AR-dependent resistance mechanisms.

Keywords: Androgen receptor; antiandrogen; cheminformatics; drug resistance; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgen Receptor Antagonists / chemistry
  • Androgen Receptor Antagonists / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Drug Discovery / methods*
  • High-Throughput Screening Assays / methods
  • Humans
  • Male
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Quantitative Structure-Activity Relationship*

Substances

  • Androgen Receptor Antagonists
  • Antineoplastic Agents