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
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Blotting, Western
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Death / drug effects
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Drug Design*
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Estrogen Receptor alpha / drug effects*
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Estrogen Receptor alpha / metabolism
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Female
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HMGB1 Protein / metabolism
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Humans
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MCF-7 Cells
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Models, Molecular
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Molecular Structure
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Proteasome Endopeptidase Complex / metabolism*
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Protein Stability
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Proteolysis
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Staining and Labeling
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Structure-Activity Relationship
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Time Factors
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Ubiquitination
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Workflow
Substances
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Antineoplastic Agents
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ESR1 protein, human
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Estrogen Receptor alpha
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HMGB1 Protein
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HMGB1 protein, human
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Proteasome Endopeptidase Complex