抗癌靶点PARP7及其抑制剂研究进展  

Progress in anti-cancer target PARP7 and its inhibitors

作　　者：赵桢煜 卢小路 李健 ZHAO Zhen-yu;LU Xiao-lu;LI Jian(Gannan Medical University,College of Pharmaceutical Sciences,Ganzhou Jiangxi 341000,China)

机构地区：[1]赣南医科大学药学院,江西赣州341000

出　　处：《中国药理学通报》2025年第4期620-625,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.82360701);江西省自然科学杰出青年基金项目(No.20212ACB216001);江西省重点研发计划项目基金(No.20203BBG73063)。

摘　　要：PARP7是一种属于PARP家族的单-ADP核糖转移酶,其作用为催化ADP核糖从NAD+转移到自身和其他底物蛋白的特定氨基酸。PARP7在许多肿瘤中过度活跃,可干预干扰素信号通路使癌细胞实现免疫逃逸。通过抑制PARP7可恢复肿瘤细胞中IFN-β表达,从而激活T细胞介导的体内抗肿瘤免疫,因此PARP7被认为是癌症治疗新的免疫调节靶点。目前,仅有1个PARP7选择性抑制剂RBN-2397进入临床Ⅰ期研究。该文重点介绍PARP7的结构、生物学功能、PARP7与癌症发生的关联性及PARP7相关抑制剂研究进展进行综述,以期为PARP7新型抑制剂的研发以及RBN-2397的结构优化提供理论基础和新思路。PARP7 is a mono-ADP ribotransferase belonging to the PARP family that acts as a specific amino acid to catalyze the transfer of ADP ribose from NAD+to itself and other substrate proteins.PARP7 is overactive in many tumors and can interfere with interferon signaling pathways to enable cancer cells to achieve immune escape.Inhibition of PARP7 can restore IFN-βexpression in tumor cells,thereby activating T cell-mediated anti-tumor immunity in vivo,so PARP7 is considered as a new immunomodulatory target for cancer therapy.At present,only one selective inhibitor of PARP7,RBN-2397,has entered phaseⅠclinical studies.This article focuses on the structure and biological function of PARP7,the correlation between PARP7 and cancer occurrence,and the research progress of PARP7-related inhibitors,in order to provide theoretical basis and new ideas for the research and development of new PARP7 inhibitors and the structural optimization of RBN-2397.

关 键 词：PARPs PARP7 monoPARPs IFN-1 抗癌靶点 PARP7小分子抑制剂 

分 类 号：R345.5[医药卫生—基础医学] R730.5R977.3