PARP抑制剂可以阻断PARP的DNA修复机制，是一类有希望的抗肿瘤治疗药物。过去十年间，FDA已经批准了几种PARP抑制剂，并有一些正在进行晚期临床研究。药物化学家们已经付出了很多努力来扩展PARP抑制剂的结构库。通过设计新的结构组合，解决了与PARP抑制剂使用相关的问题，使其在制药领域的地位令人不安。在这篇综述中，作者详细介绍了近年来进行的药物化学研究活动，包括构建PARP1/PARP2抑制剂、PARP1偏向抑制剂、PARP靶向双功能抑制剂以及PARP靶向降解剂（PROTACs）。还讨论了与FDA批准的PARP抑制剂相关的局限性以及克服这些局限性的策略。在过去十年中，PARP抑制领域已经出现了许多可行的进展。随着手头上有许多“神奇子弹”以及应对癌细胞对PARP抑制剂产生抗药性的策略不断涌现，PARP抑制剂作为有前瞻性的靶向治疗选择的主导地位很有可能很快就会得到验证。

PARP inhibitors block the DNA-repairing mechanism of PARP and represent a promising class of anti-cancer therapy. The last decade has witnessed FDA approvals of several PARP inhibitors, with some undergoing advanced-stage clinical investigation. Medicinal chemists have invested much effort to expand the structure pool of PARP inhibitors. Issues associated with the use of PARP inhibitors that make their standing disconcerting in the pharmaceutical sector have been addressed via the design of new structural assemblages.In this review, the authors present a detailed account of the medicinal chemistry campaigns conducted in the recent past for the construction of PARP1/PARP2 inhibitors, PARP1 biased inhibitors, and PARP targeting bifunctional inhibitors as well as PARP targeting degraders (PROTACs). Limitations associated with FDA-approved PARP inhibitors and strategies to outwit the limitations are also discussed.The PARP inhibitory field has been rejuvenated with numerous tractable entries in the last decade. With numerous magic bullets in hand coupled with unfolded tactics to outwit the notoriety of cancer cells developing resistance toward PARP inhibitors, the dominance of PARP inhibitors as a sagacious option of targeted therapy is highly likely to be witnessed soon.