药学学报, 2018, 53(4): 500-508
引用本文:
周仕海, 孙朋举, 赵勇强, 张岩, 余聂芳. DOT1L抑制剂在肿瘤中的研究进展[J]. 药学学报, 2018, 53(4): 500-508.
ZHOU Shi-hai, SUN Peng-ju, ZHAO Yong-qiang, ZHANG Yan, YU Nie-fang. Research progress of DOT1L inhibitors in cancer[J]. Acta Pharmaceutica Sinica, 2018, 53(4): 500-508.

DOT1L抑制剂在肿瘤中的研究进展
周仕海, 孙朋举, 赵勇强, 张岩, 余聂芳
中南大学湘雅药学院, 湖南 长沙 410013
摘要:
组蛋白H3赖氨酸79(H3K79)甲基转移酶DOT1L在激活和维持基因转录过程中起着十分重要的作用;同时,在维持个体胚胎发育和造血系统、心脏及肾脏的正常功能方面具有不可替代的作用。然而DOT1L的过表达与多种肿瘤的发生、发展密切相关,受到了广泛的关注。因此,DOT1L抑制剂的研究开发意义重大,其既可作为小分子探针,用于研究DOT1的生物学功能,也有望开发为新型抗肿瘤药物。本文就DOT1L的结构与功能、DOT1L与肿瘤的关系及DOT1L抑制剂进行综述,以期为后续研究提供参考。
关键词:    DOT1L      抑制剂      肿瘤      研究进展     
Research progress of DOT1L inhibitors in cancer
ZHOU Shi-hai, SUN Peng-ju, ZHAO Yong-qiang, ZHANG Yan, YU Nie-fang
XiangYa School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
Abstract:
Histone H3 lysine 79 (H3K79) methyltransferase DOT1L plays an important role in the activation and maintenance of gene transcription; it is also essential for maintenance of embryonic development, as well as the normal function of hematopoietic system, heart and kidney. However, the over expression of DOT1L is associated with the occurring and progress of numerous malignant tumors, so more and more attention has been paid to DOT1L. Therefore, it is of great significance to study and develop inhibitors of DOT1L. The inhibitors could serve as a tool in the investigation of the biological function, and have the potential to be developed into novel anti-cancer agents in the anticancer therapy. This paper mainly describes the structure and function of DOT1L, the relationship between DOT1L and tumors as well as the latest research progress of DOT1L inhibitors; with expect to provide some useful references for the subsequent research.
Key words:    DOT1L    inhibitor    cancer    research progress   
收稿日期: 2017-12-04
DOI: 10.16438/j.0513-4870.2017-1206
基金项目: 国家自然科学基金资助项目(81573297).
通讯作者: 余聂芳,Tel:86-731-82650485,E-mail:niefang_yu@126.com
Email: niefang_yu@126.com
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