Das Nando Dulal, Niwa Hideaki, Umehara Takashi
Laboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Epigenomes. 2023 Mar 11;7(1):7. doi: 10.3390/epigenomes7010007.
The dynamic regulation of histone methylation and demethylation plays an important role in the regulation of gene expression. Aberrant expression of histone lysine demethylases has been implicated in various diseases including intractable cancers, and thus lysine demethylases serve as promising therapeutic targets. Recent studies in epigenomics and chemical biology have led to the development of a series of small-molecule demethylase inhibitors that are potent, specific, and have in vivo efficacy. In this review, we highlight emerging small-molecule inhibitors targeting the histone lysine demethylases and their progress toward drug discovery.
组蛋白甲基化和去甲基化的动态调控在基因表达调控中发挥着重要作用。组蛋白赖氨酸去甲基化酶的异常表达与包括难治性癌症在内的多种疾病有关，因此赖氨酸去甲基化酶是很有前景的治疗靶点。表观基因组学和化学生物学的最新研究已促使一系列强效、特异且具有体内疗效的小分子去甲基化酶抑制剂得以开发。在本综述中，我们重点介绍了针对组蛋白赖氨酸去甲基化酶的新型小分子抑制剂及其在药物研发方面的进展。
