LSD1: biologic roles and therapeutic targeting

被引：169

作者：

Maiques-Diaz, Alba ^{[1
]}

Somervaille, Tim C. P. ^{[1
]}

机构：

[1] Univ Manchester, Canc Res UK Manchester Inst, Leukaemia Biol Lab, Wilmslow Rd, Manchester M20 4BX, Lancs, England

来源：

EPIGENOMICS | 2016年 / 8卷 / 08期

关键词：

acute myeloid leukemia; GSK2879552; histone demethylase; LSD1; ORY1001; small-cell lung cancer; HISTONE DEMETHYLASE LSD1; MECHANISM-BASED INACTIVATOR; STRUCTURAL BASIS; TRANSCRIPTIONAL REPRESSION; LSD1/KDM1A PROMOTES; LYSINE DEMETHYLASES; GENE ACTIVATION; SNAG DOMAIN; COREST; INHIBITION;

D O I：

10.2217/epi-2016-0009

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

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页码：1103 / 1116

页数：14

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