Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog-Thalidomide PROTACs

Molecules. 2021 Apr 26;26(9):2525. doi: 10.3390/molecules26092525.

Abstract

A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.

Keywords: PROTAC; androgen receptor (AR); bicalutamide; prostate cancer; protein degradation.

MeSH terms

  • Androgen Antagonists / chemical synthesis
  • Androgen Antagonists / chemistry*
  • Androgen Antagonists / pharmacology
  • Anilides / chemistry*
  • Anilides / pharmacology
  • Binding Sites
  • Cell Line
  • Chemistry Techniques, Synthetic
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Nitriles / chemistry*
  • Nitriles / pharmacology
  • Protein Binding
  • Proteolysis / drug effects
  • Receptors, Androgen / chemistry*
  • Receptors, Androgen / metabolism
  • Structure-Activity Relationship
  • Thalidomide / chemistry*
  • Thalidomide / pharmacology
  • Tosyl Compounds / chemistry*
  • Tosyl Compounds / pharmacology

Substances

  • AR protein, human
  • Androgen Antagonists
  • Anilides
  • Nitriles
  • Receptors, Androgen
  • Tosyl Compounds
  • Thalidomide
  • bicalutamide