LSD1: biologic roles and therapeutic targeting.
LSD1: biologic roles and therapeutic targeting.
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DOI：
10.2217/epi-2016-0009
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发表时间：
2016-08
期刊：
影响因子：
3.8
通讯作者：
Somervaille TC
中科院分区：
文献类型：
--
作者：
Maiques-Diaz A;Somervaille TC
LSD1（KDM1A；BHC110；AOF2）是第一个被报道具有组蛋白去甲基酶活性的蛋白质，此后已被证明在哺乳动物生物学中具有多种重要作用。鉴于其酶活性及其在许多人类恶性肿瘤中的高水平表达，最近的一个重要焦点是药物抑制剂的开发。在这里，我们总结了这一重要表观遗传调节因子的结构和生化知识，特别强调肿瘤学中的功能和临床前研究，这些研究为反苯环丙明衍生物LSD1抑制剂在早期临床试验中的评估提供了依据。
LSD1 (KDM1A; BHC110; AOF2) was the first protein reported to exhibit histone demethylase activity and has since been shown to have multiple essential roles in mammalian biology. Given its enzymatic activity and its high-level expression in many human malignancies, a significant recent focus has been the development of pharmacologic inhibitors. Here we summarize structural and biochemical knowledge of this important epigenetic regulator, with a particular emphasis on the functional and preclinical studies in oncology that have provided justification for the evaluation of tranylcypromine derivative LSD1 inhibitors in early phase clinical trials.