小分子 PARP 抑制剂：从 ADP-核糖基化研究工具到治疗药物。
Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation to Therapeutics.
机构信息
Program in Chemical Biology, Oregon Health & Science University, Portland, OR, 97210, USA.
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, 97210, USA.
出版信息
Curr Top Microbiol Immunol. 2019;420:211-231. doi: 10.1007/82_2018_137.
Abstract
Over the last 60 years, poly-ADP-ribose polymerases (PARPs, 17 family members in humans) have emerged as important regulators of physiology and disease. Small-molecule inhibitors have been essential tools for unraveling PARP function, and recently the first PARP inhibitors have been approved for the treatment of various human cancers. However, inhibitors have only been developed for a few PARPs and in vitro profiling has revealed that many of these exhibit polypharmacology across the PARP family. In this review, we discuss the history, development, and current state of the field, highlighting the limitations and opportunities for PARP inhibitor development.
摘要
在过去的 60 年中，聚 ADP-核糖聚合酶（PARPs，人类有 17 个家族成员）已成为生理和疾病的重要调节剂。小分子抑制剂是揭示 PARP 功能的重要工具，最近，第一批 PARP 抑制剂已被批准用于治疗各种人类癌症。然而，目前仅开发了少数几种 PARP 抑制剂，体外分析表明，这些抑制剂在 PARP 家族中具有多种药理学作用。在这篇综述中，我们讨论了该领域的历史、发展和现状，强调了 PARP 抑制剂开发的局限性和机遇。
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