Kaniskan H Ümit, Jin Jian
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Curr Opin Chem Biol. 2017 Aug;39:100-108. doi: 10.1016/j.cbpa.2017.06.013. Epub 2017 Jun 26.
Mounting evidence suggests that protein methyltransferases (PMTs), which catalyze methylation of histones as well as non-histone proteins, play a crucial role in diverse biological pathways and human diseases. In particular, PMTs have been recognized as major players in regulating gene expression and chromatin state. There has been an increasingly growing interest in these enzymes as potential therapeutic targets and over the past two years tremendous progress has been made in the discovery of selective, small molecule inhibitors of protein lysine and arginine methyltransferases. Inhibitors of PMTs have been used extensively in oncology studies as tool compounds, and inhibitors of EZH2, DOT1L and PRMT5 are currently in clinical trials.
越来越多的证据表明，催化组蛋白以及非组蛋白甲基化的蛋白质甲基转移酶（PMT）在多种生物途径和人类疾病中发挥着关键作用。特别是，PMT已被认为是调节基因表达和染色质状态的主要参与者。作为潜在的治疗靶点，人们对这些酶的兴趣日益浓厚，在过去两年中，在发现蛋白质赖氨酸和精氨酸甲基转移酶的选择性小分子抑制剂方面取得了巨大进展。PMT抑制剂已作为工具化合物广泛用于肿瘤学研究，目前EZH2、DOT1L和PRMT5的抑制剂正在进行临床试验。
