靶向分子癌症治疗显著改善患者结果，尽管它们的有效性的持久性可能受到限制。对这些治疗的抵抗通常与靶向癌蛋白上的适应性变化有关，这些变化降低了结合亲和力。此外，针对癌症的靶向治疗武器缺乏覆盖几个有挑战性特征的臭名昭着的癌蛋白。分解剂是一种相对较新的治疗模式，它通过劫持细胞蛋白质破坏机制来消耗目标蛋白质。分解剂为癌症治疗提供了几个优势，包括对目标蛋白质获取突变的弹性，增强的选择性，较低的剂量要求以及消除致癌转录因子和框架蛋白的潜力。在本文中，我们回顾了针对特定癌症治疗靶点的蛋白酶靶向嵌合体（PROTAC）的开发和报道的生物活性。PROTAC设计的药物化学一直是积极研究的一个具有挑战性的领域，但该领域的最新进展将开创理性降解剂设计的时代。© 2023。这是美国政府的工作，不受美国版权保护；可能适用外国版权保护。

Molecularly targeted cancer therapies substantially improve patient outcomes, although the durability of their effectiveness can be limited. Resistance to these therapies is often related to adaptive changes in the target oncoprotein which reduce binding affinity. The arsenal of targeted cancer therapies, moreover, lacks coverage of several notorious oncoproteins with challenging features for inhibitor development. Degraders are a relatively new therapeutic modality which deplete the target protein by hijacking the cellular protein destruction machinery. Degraders offer several advantages for cancer therapy including resiliency to acquired mutations in the target protein, enhanced selectivity, lower dosing requirements, and the potential to abrogate oncogenic transcription factors and scaffolding proteins. Herein, we review the development of proteolysis targeting chimeras (PROTACs) for selected cancer therapy targets and their reported biological activities. The medicinal chemistry of PROTAC design has been a challenging area of active research, but the recent advances in the field will usher in an era of rational degrader design.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.