Molecular Design, Synthesis, and Evaluation of SNIPER(ER) That Induces Proteasomal Degradation of ERα

Methods Mol Biol. 2016:1366:549-560. doi: 10.1007/978-1-4939-3127-9_42.

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 recently developed a novel small molecule SNIPER(ER) that targets 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 system.

Keywords: Cell death; Estrogen receptor; Protein knockdown; SNIPER; Ubiquitin–proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Death / drug effects
  • Drug Design*
  • Estrogen Receptor alpha / drug effects*
  • Estrogen Receptor alpha / metabolism
  • Female
  • HMGB1 Protein / metabolism
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Structure
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Stability
  • Proteolysis
  • Staining and Labeling
  • Structure-Activity Relationship
  • Time Factors
  • Ubiquitination
  • Workflow

Substances

  • Antineoplastic Agents
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • HMGB1 Protein
  • HMGB1 protein, human
  • Proteasome Endopeptidase Complex