组蛋白赖氨酸甲基转移酶作为抗癌药物研发的靶点
Histone lysine methyltransferases as anti-cancer targets for drug discovery.
作者信息
Liu Qing, Wang Ming-Wei
机构信息
The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
The National Center for Drug Screening, Shanghai 201203, China.
出版信息
Acta Pharmacol Sin. 2016 Sep;37(10):1273-1280. doi: 10.1038/aps.2016.64. Epub 2016 Jul 11.
Abstract
Post-translational epigenetic modification of histones is controlled by a number of histone-modifying enzymes. Such modification regulates the accessibility of DNA and the subsequent expression or silencing of a gene. Human histone methyltransferases (HMTs)constitute a large family that includes histone lysine methyltransferases (HKMTs) and histone/protein arginine methyltransferases (PRMTs). There is increasing evidence showing a correlation between HKMTs and cancer pathogenesis. Here, we present an overview of representative HKMTs, including their biological and biochemical properties as well as the profiles of small molecule inhibitors for a comprehensive understanding of HKMTs in drug discovery.
摘要
组蛋白的翻译后表观遗传修饰由多种组蛋白修饰酶控制。这种修饰调节DNA的可及性以及随后基因的表达或沉默。人类组蛋白甲基转移酶（HMTs）构成一个大家族，其中包括组蛋白赖氨酸甲基转移酶（HKMTs）和组蛋白/蛋白质精氨酸甲基转移酶（PRMTs）。越来越多的证据表明HKMTs与癌症发病机制之间存在关联。在此，我们概述了具有代表性的HKMTs，包括它们的生物学和生化特性以及小分子抑制剂概况，以便在药物研发中全面了解HKMTs。
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本文引用的文献
1
The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat.
J Med Chem. 2016 Feb 25;59(4):1556-64. doi: 10.1021/acs.jmedchem.5b01501. Epub 2016 Jan 27.
2
EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression.
Blood. 2015 Oct 15;126(16):1930-9. doi: 10.1182/blood-2015-06-649087. Epub 2015 Aug 28.
3
H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance.
J Immunol. 2015 Aug 15;195(4):1868-82. doi: 10.4049/jimmunol.1402243. Epub 2015 Jul 1.
4
Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.
ACS Med Chem Lett. 2015 Apr 29;6(6):695-700. doi: 10.1021/acsmedchemlett.5b00124. eCollection 2015 Jun 11.
5
Dot1 histone methyltransferases share a distributive mechanism but have highly diverged catalytic properties.
Sci Rep. 2015 May 12;5:9824. doi: 10.1038/srep09824.
6
LLY-507, a Cell-active, Potent, and Selective Inhibitor of Protein-lysine Methyltransferase SMYD2.
J Biol Chem. 2015 May 29;290(22):13641-53. doi: 10.1074/jbc.M114.626861. Epub 2015 Mar 30.
7
Homocysteine and DNA methylation: a review of animal and human literature.
Mol Genet Metab. 2014 Dec;113(4):243-52. doi: 10.1016/j.ymgme.2014.10.006. Epub 2014 Oct 14.
8
Analogues of the Natural Product Sinefungin as Inhibitors of EHMT1 and EHMT2.
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9
Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2.
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SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor.
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