Inhibition of PARP1 is a proven strategy for the treatment of various cancers. We used our DNA-encoded library platform, comprising ~5 billion molecules, to screen multiple PARP1 protein constructs, including one with the autoinhibitory helical domain removed to mimic a biologically relevant conformation. The experimental design allowed us to find novel and potent isoindolinone PARP1 inhibitors that do not exhibit toxic DNA-trapping properties.

中文翻译：

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使用 DNA 编码文库发现针对 PARP1 活性构象的强效异吲哚酮抑制剂

抑制 PARP1 是一种行之有效的治疗多种癌症的策略。我们使用包含约 50 亿个分子的 DNA 编码文库平台来筛选多种 PARP1 蛋白构建体，其中包括一种去除了自抑制螺旋结构域以模拟生物学相关构象的构建体。实验设计使我们能够找到新型、有效的异吲哚啉酮 PARP1 抑制剂，该抑制剂不表现出有毒的 DNA 捕获特性。