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本文引用的文献

1
High Expression of Nicotinamide N-Methyltransferase in Patients with Sporadic Alzheimer's Disease.烟酰胺N-甲基转移酶在散发性阿尔茨海默病患者中的高表达
Mol Neurobiol. 2021 Apr;58(4):1769-1781. doi: 10.1007/s12035-020-02259-9. Epub 2021 Jan 2.
2
Development of fluorescence polarization-based competition assay for nicotinamide N-methyltransferase.基于荧光偏振竞争法的烟酰胺 N-甲基转移酶的研制。
Anal Biochem. 2020 Sep 1;604:113833. doi: 10.1016/j.ab.2020.113833. Epub 2020 Jul 2.
3
Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogues.利用双底物类似物探究蛋白质N-末端甲基转移酶1活性位点的可塑性
J Med Chem. 2020 Aug 13;63(15):8419-8431. doi: 10.1021/acs.jmedchem.0c00770. Epub 2020 Jul 16.
4
Optimization of High-Throughput Methyltransferase Assays for the Discovery of Small Molecule Inhibitors.高通量甲基转移酶测定法的优化及其在小分子抑制剂发现中的应用。
ACS Comb Sci. 2020 Aug 10;22(8):422-432. doi: 10.1021/acscombsci.0c00077. Epub 2020 Jun 27.
5
ER stress-induced upregulation of NNMT contributes to alcohol-related fatty liver development.内质网应激诱导 NNMT 的上调促进了酒精相关性脂肪肝的发生发展。
J Hepatol. 2020 Oct;73(4):783-793. doi: 10.1016/j.jhep.2020.04.038. Epub 2020 May 7.
6
Novel Propargyl-Linked Bisubstrate Analogues as Tight-Binding Inhibitors for Nicotinamide -Methyltransferase.新型炔丙基连接双底物类似物作为烟酰胺 -N- 甲基转移酶的紧密结合抑制剂。
J Med Chem. 2019 Dec 12;62(23):10783-10797. doi: 10.1021/acs.jmedchem.9b01255. Epub 2019 Dec 3.
7
High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide -Methyltransferase (NNMT).高亲和性炔基双底物抑制剂烟酰胺 -N- 甲基转移酶(NNMT)。
J Med Chem. 2019 Nov 14;62(21):9837-9873. doi: 10.1021/acs.jmedchem.9b01238. Epub 2019 Oct 25.
8
Bisubstrate Inhibitors of Nicotinamide -Methyltransferase (NNMT) with Enhanced Activity.双底物抑制剂的烟酰胺 -N- 甲基转移酶 (NNMT),具有增强的活性。
J Med Chem. 2019 Jul 25;62(14):6597-6614. doi: 10.1021/acs.jmedchem.9b00413. Epub 2019 Jul 12.
9
Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening.通过亲电片段筛选快速发现共价探针。
J Am Chem Soc. 2019 Jun 5;141(22):8951-8968. doi: 10.1021/jacs.9b02822. Epub 2019 May 22.
10
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.蛋白质组学揭示 NNMT 是癌症相关成纤维细胞的代谢调控大师。
Nature. 2019 May;569(7758):723-728. doi: 10.1038/s41586-019-1173-8. Epub 2019 May 1.

烟酰胺甲基转移酶的作用机制与抑制剂

Mechanisms and inhibitors of nicotinamide -methyltransferase.

作者信息

Iyamu Iredia D, Huang Rong

机构信息

Department of Medicinal Chemistry and Molecular Pharmacology, Center for Cancer Research, Institute for Drug Discovery, Purdue University West Lafayette Indiana 47907 USA

出版信息

RSC Med Chem. 2021 May 19;12(8):1254-1261. doi: 10.1039/d1md00016k. eCollection 2021 Aug 18.

DOI:10.1039/d1md00016k
PMID:34458733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8372200/
Abstract

Nicotinamide -methyltransferase (NNMT) plays an important role in diverse biological processes by regulating methylation potential and the degradation of nicotinamide. Meanwhile, the aberrant expression of NNMT has been implicated in multiple cancers, metabolic and liver diseases. Therefore, there has been an emerging interest in assessing NNMT as a potential therapeutic target and discovering NNMT inhibitors over the past 5 years. Herein, we focus on the recognition, mechanism, and inhibitors of NNMT with emphasis on key advancements in the field. We also discuss future directions for the development of NNMT inhibitors.

摘要

烟酰胺甲基转移酶(NNMT)通过调节甲基化潜能和烟酰胺的降解,在多种生物学过程中发挥重要作用。同时,NNMT的异常表达与多种癌症、代谢性疾病和肝脏疾病有关。因此,在过去5年里,人们对评估NNMT作为潜在治疗靶点以及发现NNMT抑制剂的兴趣日益浓厚。在此,我们重点关注NNMT的识别、作用机制和抑制剂,着重介绍该领域的关键进展。我们还讨论了NNMT抑制剂开发的未来方向。