Molecular Design, Synthesis, and Evaluation of SNIPER (ER) that Induces Targeted Protein Degradation of ERα

Methods Mol Biol. 2022:2418:363-382. doi: 10.1007/978-1-0716-1920-9_20.

Abstract

Manipulation of protein stability using small molecules has a great potential for both basic research and clinical therapy. Based on our protein knockdown technology, we developed chimeric degrader molecules SNIPER(ER)s that target the estrogen receptor alpha (ERα) for degradation via the ubiquitin-proteasome system. This chapter describes the design and synthesis of SNIPER(ER) compounds and methods for the evaluation of their activity in cellular systems and in a tumor xenograft model.

Keywords: Antitumor activity; Cell death; Estrogen receptor; Protein knockdown; SNIPER; Ubiquitin-proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms*
  • Cell Line, Tumor
  • Estrogen Receptor alpha* / genetics
  • Estrogen Receptor alpha* / metabolism
  • Female
  • Humans
  • Mice
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Ubiquitin / metabolism
  • Ubiquitination

Substances

  • Estrogen Receptor alpha
  • Ubiquitin
  • Proteasome Endopeptidase Complex