Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital , 262 Danny Thomas Place, MS1000, Memphis, Tennessee 38105, United States.
J Med Chem. 2017 Dec 28;60(24):9932-9959. doi: 10.1021/acs.jmedchem.7b00358. Epub 2017 Jul 12.
This review article discusses some insights about generating novel mechanistic inhibitors of the DNA damage response and repair (DDR) pathways by focusing on protein-protein interactions (PPIs) of the key DDR components. General requirements for PPI strategies, such as selecting the target PPI site on the basis of its functionality, are discussed first. Next, on the basis of functional rationale and biochemical feasibility to identify a PPI inhibitor, 26 PPIs in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discussed for inhibitor discovery to benefit cancer therapies using a DNA-damaging agent.
这篇综述文章讨论了通过关注关键 DDR 成分的蛋白质-蛋白质相互作用 (PPI) 来生成新型 DNA 损伤反应和修复 (DDR) 途径的机制抑制剂的一些见解。首先讨论了 PPI 策略的一般要求，例如根据其功能选择靶 PPI 位点。接下来，基于功能原理和生化可行性来确定 PPI 抑制剂，专门讨论了 DDR 途径中的 26 个 PPI（BER、MMR、NER、NHEJ、HR、TLS 和 ICL 修复），以发现抑制剂用于使用 DNA 损伤剂的癌症治疗。
