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<p>Recent discoveries have highlighted that small monovalent molecules can leverage a variety of cellular mechanisms to induce degradation of a specific target protein. This perspective exemplifies and contextualizes these mechanisms within drug discovery, with a focus on identification of novel monovalent degraders via cell-based high-throughput screening (HTS) methodologies. Considerations for screening strategies, assay technologies and mechanistic deconvolution are discussed, with emphasis on identification of degrader compounds from diverse compound collections.</p>

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Mechanisms that matter: unbiased cellular screening for degraders

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月17日

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  • Helen E. Burston,
  • Elizabeth M. Rosethorne,
  • Francesca Cavallo,
  • Allan Jordan,
  • Prasamit S. Baruah,
  • Denise Swift,
  • Roland Hjerpe

摘要

Recent discoveries have highlighted that small monovalent molecules can leverage a variety of cellular mechanisms to induce degradation of a specific target protein. This perspective exemplifies and contextualizes these mechanisms within drug discovery, with a focus on identification of novel monovalent degraders via cell-based high-throughput screening (HTS) methodologies. Considerations for screening strategies, assay technologies and mechanistic deconvolution are discussed, with emphasis on identification of degrader compounds from diverse compound collections.