以RecQ家族解旋酶为靶点的抗癌活性分子研究进展  

Research progress on anti-cancer active moleculestargeting RecQ family helicase

作　　者：高海琳 曾家颖 袁昊 吴璧含 周盈宸 陈硕斌 GAO Hai-lin;ZENG Jia-ying;YUAN Hao;WU Bi-han;ZHOU Ying-chen;CHEN Shuo-bin*(School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China)

机构地区：[1]中山大学药学院,广东广州510006

出　　处：《中国药物化学杂志》2023年第10期770-782,共13页Chinese Journal of Medicinal Chemistry

基　　金：广东省自然科学基金杰出青年项目(2019B151502015);国家自然科学基金面上项目(22377153)。

摘　　要：RecQ解旋酶家族成员是一类具有ATP依赖性的DNA解旋酶,可以解散包括双链、霍利迪结等多种核酸高级结构。研究表明,RecQ解旋酶家族成员活性的异常与癌症的发生发展存在重要关联。抑制家族成员如BLM、WRN的活性可选择性杀伤特定类型的癌细胞,提示该家族蛋白可能是潜在抗癌新靶标。本综述将介绍蛋白成员结构与功能的特点,结合分子模拟技术比较蛋白的不同结构域中的潜在结合位点,总结以RecQ解旋酶为靶点的小分子抑制剂的发现与相关药物化学生物学研究现状,探讨以RecQ解旋酶为靶点的抗癌先导化合物发现策略与应用前景。The RecQ helicase family is a class of ATP-dependent DNA helicases that can dissolve a variety of nucleic acid advanced structures,including double-stranded DNA and Holliday junctions.Abnormalities in the activity of RecQ helicase family members have been associated with the occurrence and development of cancer.Inhibiting the activity of family members such as BLM and WRN can selectively kill specific types of cancer cells,suggesting that this family of proteins could serve as potential targets for cancer treatment.This review will discuss the structure and function of RecQ helicase family members,compare the potential binding sites within different structural domains of the protein using molecular simulation technology,and explore the discovery strategy and application prospects of anticancer lead compounds targeting RecQ helicase,basing on the current status of small molecule inhibitors and related research in medicinal chemical biology targeting RecQ helicase.

关 键 词：RecQ解旋酶 癌症 解旋酶抑制剂 合成致死 药物化学生物学 

分 类 号：R914[医药卫生—药物化学]