• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

DNA甲基化靶向：DNMT/HMT串扰挑战

DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge.

作者信息

Castillo-Aguilera Omar, Depreux Patrick, Halby Ludovic, Arimondo Paola B, Goossens Laurence

机构信息

Univ. Lille, ICPAL, EA 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, 3 rue du Pr. Laguesse, F-59000 Lille, France.

FRE3600 Epigenetic Targeting of Cancer, CNRS, 31035 Toulouse, France.

出版信息

Biomolecules. 2017 Jan 5;7(1):3. doi: 10.3390/biom7010003.

DOI:10.3390/biom7010003
PMID:28067760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5372715/
Abstract

Chromatin can adopt a decondensed state linked to gene transcription (euchromatin) and a condensed state linked to transcriptional repression (heterochromatin). These states are controlled by epigenetic modulators that are active on either the DNA or the histones and are tightly associated to each other. Methylation of both DNA and histones is involved in either the activation or silencing of genes and their crosstalk. Since DNA/histone methylation patterns are altered in cancers, molecules that target these modifications are interesting therapeutic tools. We present herein a vast panel of DNA methyltransferase inhibitors classified according to their mechanism, as well as selected histone methyltransferase inhibitors sharing a common mode of action.

摘要

染色质可呈现与基因转录相关的解聚状态（常染色质）和与转录抑制相关的凝聚状态（异染色质）。这些状态由对DNA或组蛋白起作用且彼此紧密相关的表观遗传调节剂控制。DNA和组蛋白的甲基化都参与基因的激活或沉默及其相互作用。由于癌症中DNA/组蛋白甲基化模式会发生改变，靶向这些修饰的分子是很有前景的治疗工具。我们在此展示了根据作用机制分类的大量DNA甲基转移酶抑制剂，以及具有共同作用模式的选定组蛋白甲基转移酶抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/4cfe5ef1c663/biomolecules-07-00003-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/b72a54d1ba9a/biomolecules-07-00003-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/4d1a626ec196/biomolecules-07-00003-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/2ad937ce680e/biomolecules-07-00003-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/a36de9cb4256/biomolecules-07-00003-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/4cfe5ef1c663/biomolecules-07-00003-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/b72a54d1ba9a/biomolecules-07-00003-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/4d1a626ec196/biomolecules-07-00003-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/2ad937ce680e/biomolecules-07-00003-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/a36de9cb4256/biomolecules-07-00003-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eae0/5372715/4cfe5ef1c663/biomolecules-07-00003-g005.jpg

相似文献

1
DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge.DNA甲基化靶向：DNMT/HMT串扰挑战
Biomolecules. 2017 Jan 5;7(1):3. doi: 10.3390/biom7010003.
2
Epigenetic small molecule modulators of histone and DNA methylation.组蛋白和 DNA 甲基化的表观遗传小分子调节剂。
Curr Opin Chem Biol. 2018 Aug;45:73-85. doi: 10.1016/j.cbpa.2018.03.003. Epub 2018 Mar 24.
3
Development of DNA methyltransferase inhibitors for the treatment of neoplastic diseases.用于治疗肿瘤疾病的DNA甲基转移酶抑制剂的研发。
Curr Med Chem. 2009;16(17):2075-85. doi: 10.2174/092986709788612738.
4
Histone methyltransferase inhibitors: novel epigenetic agents for cancer treatment.组蛋白甲基转移酶抑制剂：癌症治疗的新型表观遗传药物。
Curr Med Chem. 2013;20(2):167-85. doi: 10.2174/092986713804806667.
5
Reversing aberrant methylation patterns in cancer.逆转癌症中的异常甲基化模式。
Curr Med Chem. 2010;17(13):1246-54. doi: 10.2174/092986710790936329.
6
Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy.在癌症治疗临床试验中靶向组蛋白甲基转移酶和去甲基酶。
Clin Epigenetics. 2016 May 24;8:57. doi: 10.1186/s13148-016-0223-4. eCollection 2016.
7
Histone modification therapy of cancer.癌症的组蛋白修饰治疗。
Adv Genet. 2010;70:341-86. doi: 10.1016/B978-0-12-380866-0.60013-7.
8
DNA Methyltransferase Inhibitors and their Therapeutic Potential.DNA 甲基转移酶抑制剂及其治疗潜力。
Curr Top Med Chem. 2018;18(28):2448-2457. doi: 10.2174/1568026619666181120150122.
9
Epigenetic response to environmental stress: Assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts.对环境应激的表观遗传反应：病理应激心脏中Myh6启动子上BRG1 - G9a/GLP - DNMT3抑制性染色质复合物的组装。
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1772-81. doi: 10.1016/j.bbamcr.2016.03.002. Epub 2016 Mar 4.
10
Interaction between DNA/histone methyltransferases and their inhibitors.DNA/组蛋白甲基转移酶与其抑制剂之间的相互作用。
Curr Med Chem. 2015;22(3):360-72. doi: 10.2174/0929867321666141106114538.

引用本文的文献

1
Epigenetic Mechanisms Governing Nrf2 Expression and Its Role in Ferroptosis.调控Nrf2表达的表观遗传机制及其在铁死亡中的作用。
Biomedicines. 2025 Aug 5;13(8):1913. doi: 10.3390/biomedicines13081913.
2
Epigenetic Regulation of Neutrophils in ARDS.急性呼吸窘迫综合征中中性粒细胞的表观遗传调控
Cells. 2025 Jul 25;14(15):1151. doi: 10.3390/cells14151151.
3
Beyond Genes: Mechanistic and Epidemiological Insights into Paternal Environmental Influence on Offspring Health.超越基因：父亲环境对后代健康影响的机制与流行病学见解

本文引用的文献

1
Editing DNA Methylation in the Mammalian Genome.编辑哺乳动物基因组中的DNA甲基化
Cell. 2016 Sep 22;167(1):233-247.e17. doi: 10.1016/j.cell.2016.08.056.
2
A cross-talk between DNA methylation and H3 lysine 9 dimethylation at the KvDMR1 region controls the induction of Cdkn1c in muscle cells.KvDMR1区域的DNA甲基化与H3赖氨酸9二甲基化之间的相互作用控制着肌肉细胞中Cdkn1c的诱导。
Epigenetics. 2016 Nov;11(11):791-803. doi: 10.1080/15592294.2016.1230576. Epub 2016 Sep 9.
3
Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach.
Curr Environ Health Rep. 2025 Aug 9;12(1):29. doi: 10.1007/s40572-025-00488-5.
4
Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.将表观遗传调节因子作为克服癌症治疗耐药性的一条有前景的途径。
Signal Transduct Target Ther. 2025 Jul 18;10(1):219. doi: 10.1038/s41392-025-02266-z.
5
The advances of DNA methylation in the liquid biopsy for the detection of lung cancer.DNA甲基化在肺癌检测液体活检中的进展
Front Oncol. 2025 Jul 1;15:1547797. doi: 10.3389/fonc.2025.1547797. eCollection 2025.
6
Mechanism of crosstalk between DNA methylation and histone acetylation and related advances in diagnosis and treatment of premature ovarian failure.DNA甲基化与组蛋白乙酰化之间的串扰机制及卵巢早衰诊断与治疗的相关进展
Epigenetics. 2025 Dec;20(1):2528563. doi: 10.1080/15592294.2025.2528563. Epub 2025 Jul 7.
7
Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review.脓毒症相关急性肾损伤中DNA甲基化的分子见解及临床意义：一项叙述性综述
BMC Nephrol. 2025 May 22;26(1):253. doi: 10.1186/s12882-025-04179-z.
8
A Review on the Impact of Aberrant Methylation in Breast Cancer: Diagnostic, Prognostic, and Therapeutic Approaches.乳腺癌中异常甲基化的影响综述：诊断、预后及治疗方法
Iran J Biotechnol. 2024 Oct 1;22(4):e3897. doi: 10.30498/ijb.2024.447513.3897. eCollection 2024 Oct.
9
Kaempferol Targets Global Epigenetic Modifiers to Impedes Growth and Migratory Ability of HeLa Cells.山奈酚靶向全局表观遗传修饰因子以抑制HeLa细胞的生长和迁移能力。
J Cell Mol Med. 2025 Apr;29(7):e70498. doi: 10.1111/jcmm.70498.
10
Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs.嘧啶苄酰胺和嘧啶噻吩酰胺衍生物作为DOT1L及相关表观遗传靶点DNMT3a、PRMT4和其他组蛋白甲基转移酶抑制剂的设计、合成与评价
RSC Med Chem. 2025 Jan 30. doi: 10.1039/d4md00899e.
通过基于结构的片段化方法发现新型Dot1L抑制剂。
ACS Med Chem Lett. 2016 Jun 1;7(8):735-40. doi: 10.1021/acsmedchemlett.6b00167. eCollection 2016 Aug 11.
4
Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket.基于片段筛选命中物向在诱导结合口袋中相互作用的强效DOT1L抑制剂的优化。
ACS Med Chem Lett. 2016 Jun 6;7(8):730-4. doi: 10.1021/acsmedchemlett.6b00168. eCollection 2016 Aug 11.
5
Recently discovered EZH2 and EHMT2 (G9a) inhibitors.最近发现的EZH2和EHMT2（G9a）抑制剂。
Future Med Chem. 2016 Sep;8(13):1635-54. doi: 10.4155/fmc-2016-0096. Epub 2016 Aug 22.
6
H3K36 methyltransferases as cancer drug targets: rationale and perspectives for inhibitor development.H3K36甲基转移酶作为癌症药物靶点：抑制剂开发的理论依据与前景
Future Med Chem. 2016 Sep;8(13):1589-607. doi: 10.4155/fmc-2016-0071. Epub 2016 Aug 22.
7
Allosteric control of mammalian DNA methyltransferases - a new regulatory paradigm.哺乳动物DNA甲基转移酶的变构调控——一种新的调控模式。
Nucleic Acids Res. 2016 Oct 14;44(18):8556-8575. doi: 10.1093/nar/gkw723. Epub 2016 Aug 12.
8
New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile as a non-traditional replacement for heavy halogen atoms.新型组蛋白甲基转移酶DOT1L小分子抑制剂，以腈基作为重卤素原子的非传统替代基团。
Bioorg Med Chem Lett. 2016 Sep 15;26(18):4518-4522. doi: 10.1016/j.bmcl.2016.07.041. Epub 2016 Jul 21.
9
Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation.蛋白质精氨酸甲基转移酶5调节多种信号通路以促进肺癌细胞增殖。
BMC Cancer. 2016 Aug 2;16:567. doi: 10.1186/s12885-016-2632-3.
10
Influence of Repressive Histone and DNA Methylation upon D4Z4 Transcription in Non-Myogenic Cells.抑制性组蛋白和DNA甲基化对非成肌细胞中D4Z4转录的影响。
PLoS One. 2016 Jul 28;11(7):e0160022. doi: 10.1371/journal.pone.0160022. eCollection 2016.