• 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

从头设计 DNA 甲基转移酶 1 抑制剂：配体和基于结构方法的关键比较。

De Novo Design of Inhibitors of DNA Methyltransferase 1: A Critical Comparison of Ligand- and Structure-Based Approaches.

机构信息

DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico.

División Académica de Ciencias Básicas, Universidad Juárez Autónoma de Tabasco, Carretera Cunduacán-Jalpa de Méndez, Km 1, Cunduacán 86690, Tabasco, Mexico.

出版信息

Biomolecules. 2024 Jun 28;14(7):775. doi: 10.3390/biom14070775.

DOI:10.3390/biom14070775
PMID:39062489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11274800/
Abstract

Designing and developing inhibitors against the epigenetic target DNA methyltransferase (DNMT) is an attractive strategy in epigenetic drug discovery. DNMT1 is one of the epigenetic enzymes with significant clinical relevance. Structure-based de novo design is a drug discovery strategy that was used in combination with similarity searching to identify a novel DNMT inhibitor with a novel chemical scaffold and warrants further exploration. This study aimed to continue exploring the potential of de novo design to build epigenetic-focused libraries targeted toward DNMT1. Herein, we report the results of an in-depth and critical comparison of ligand- and structure-based de novo design of screening libraries focused on DNMT1. The newly designed chemical libraries focused on DNMT1 are freely available on GitHub.

摘要

设计和开发针对表观遗传靶点 DNA 甲基转移酶 (DNMT) 的抑制剂是表观遗传药物发现中的一种有吸引力的策略。DNMT1 是具有重要临床相关性的表观遗传酶之一。基于结构的从头设计是一种药物发现策略，与相似性搜索相结合，用于鉴定具有新型化学支架的新型 DNMT 抑制剂，值得进一步探索。本研究旨在继续探索从头设计在构建针对 DNMT1 的以表观遗传学为重点的文库方面的潜力。在此，我们报告了深入和批判性比较针对 DNMT1 的基于配体和基于结构的从头设计筛选文库的结果。新设计的针对 DNMT1 的化学文库可在 GitHub 上免费获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d941b855b906/biomolecules-14-00775-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d70daa0d0a3a/biomolecules-14-00775-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/44df6a4171a5/biomolecules-14-00775-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/2bc03d70453e/biomolecules-14-00775-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/01969416899f/biomolecules-14-00775-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/98f661230f11/biomolecules-14-00775-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/81a4b189d410/biomolecules-14-00775-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/49fc7bd7d873/biomolecules-14-00775-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/6a8ac81aa22a/biomolecules-14-00775-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/2b95fe964b91/biomolecules-14-00775-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d5013279552e/biomolecules-14-00775-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/7bbf1459efb1/biomolecules-14-00775-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d861f429350f/biomolecules-14-00775-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/b39cda6a0c18/biomolecules-14-00775-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/46c08a81cbcf/biomolecules-14-00775-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/84251187ca75/biomolecules-14-00775-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/93acbae9f415/biomolecules-14-00775-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/80df759441a3/biomolecules-14-00775-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/65cd16a7afeb/biomolecules-14-00775-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d941b855b906/biomolecules-14-00775-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d70daa0d0a3a/biomolecules-14-00775-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/44df6a4171a5/biomolecules-14-00775-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/2bc03d70453e/biomolecules-14-00775-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/01969416899f/biomolecules-14-00775-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/98f661230f11/biomolecules-14-00775-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/81a4b189d410/biomolecules-14-00775-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/49fc7bd7d873/biomolecules-14-00775-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/6a8ac81aa22a/biomolecules-14-00775-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/2b95fe964b91/biomolecules-14-00775-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d5013279552e/biomolecules-14-00775-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/7bbf1459efb1/biomolecules-14-00775-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d861f429350f/biomolecules-14-00775-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/b39cda6a0c18/biomolecules-14-00775-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/46c08a81cbcf/biomolecules-14-00775-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/84251187ca75/biomolecules-14-00775-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/93acbae9f415/biomolecules-14-00775-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/80df759441a3/biomolecules-14-00775-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/65cd16a7afeb/biomolecules-14-00775-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac80/11274800/d941b855b906/biomolecules-14-00775-g019.jpg

相似文献

1
De Novo Design of Inhibitors of DNA Methyltransferase 1: A Critical Comparison of Ligand- and Structure-Based Approaches.从头设计 DNA 甲基转移酶 1 抑制剂：配体和基于结构方法的关键比较。
Biomolecules. 2024 Jun 28;14(7):775. doi: 10.3390/biom14070775.
2
Identification of potent inhibitors of DNA methyltransferase 1 (DNMT1) through a pharmacophore-based virtual screening approach.通过基于药效团的虚拟筛选方法鉴定DNA甲基转移酶1（DNMT1）的有效抑制剂。
J Mol Graph Model. 2017 Aug;75:174-188. doi: 10.1016/j.jmgm.2017.05.014. Epub 2017 May 25.
3
Docking of a novel DNA methyltransferase inhibitor identified from high-throughput screening: insights to unveil inhibitors in chemical databases.从高通量筛选中鉴定新型 DNA 甲基转移酶抑制剂的对接：揭示化学数据库中抑制剂的见解。
Mol Divers. 2013 May;17(2):337-44. doi: 10.1007/s11030-013-9428-z. Epub 2013 Feb 28.
4
Towards the chemoinformatic-based identification of DNA methyltransferase inhibitors: 2D- and 3D-similarity profile of screening libraries.迈向基于化学信息学的DNA甲基转移酶抑制剂鉴定：筛选文库的二维和三维相似性概况
Curr Comput Aided Drug Des. 2012 Dec 1;8(4):317-29. doi: 10.2174/157340912803519606.
5
7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1.基于表观遗传学靶点文库的 7-烷氧基喹唑啉类化合物是 DNA 甲基转移酶 1 的高效和选择性抑制剂。
Molecules. 2022 Apr 30;27(9):2892. doi: 10.3390/molecules27092892.
6
Identification of DNA Methyltransferase-1 Inhibitor for Breast Cancer Therapy through Computational Fragment-Based Drug Design.通过基于片段的计算药物设计鉴定用于乳腺癌治疗的 DNA 甲基转移酶-1 抑制剂。
Molecules. 2021 Jan 13;26(2):375. doi: 10.3390/molecules26020375.
7
A novel class of selective non-nucleoside inhibitors of human DNA methyltransferase 3A.一种新型的选择性非核苷类人 DNA 甲基转移酶 3A 抑制剂。
Bioorg Med Chem Lett. 2021 May 15;40:127908. doi: 10.1016/j.bmcl.2021.127908. Epub 2021 Mar 8.
8
Effect of Withaferin-A, Withanone, and Caffeic Acid Phenethyl Ester on DNA Methyltransferases: Potential in Epigenetic Cancer Therapy.维甲酰胺-A、醉茄内酯和咖啡酸苯乙酯对 DNA 甲基转移酶的影响：在表观遗传学癌症治疗中的潜力。
Curr Top Med Chem. 2024;24(4):379-391. doi: 10.2174/1568026623666230726105017.
9
Drug Design of Targeted Chemical Libraries Based on Artificial Intelligence and Pair-Based Multiobjective Optimization.基于人工智能和基于对的多目标优化的靶向化学库药物设计。
J Chem Inf Model. 2020 Oct 26;60(10):4582-4593. doi: 10.1021/acs.jcim.0c00517. Epub 2020 Sep 9.
10
Molecular modeling of inhibitors of human DNA methyltransferase with a crystal structure: discovery of a novel DNMT1 inhibitor.具有晶体结构的人 DNA 甲基转移酶抑制剂的分子建模：新型 DNMT1 抑制剂的发现。
Adv Protein Chem Struct Biol. 2012;87:219-47. doi: 10.1016/B978-0-12-398312-1.00008-1.

引用本文的文献

1
In-Silico discovery of novel cephalosporin antibiotic conformers via ligand-based pharmacophore modelling and de novo molecular design.通过基于配体的药效团建模和从头分子设计在计算机上发现新型头孢菌素抗生素构象体。
J Genet Eng Biotechnol. 2025 Sep;23(3):100514. doi: 10.1016/j.jgeb.2025.100514. Epub 2025 Jun 3.

本文引用的文献

1
Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study.解析麦胚凝集素及其分离结构域结构稳定性的调控机制：一种联合量热法、NMR 和 MD 模拟研究。
Protein Sci. 2024 Jun;33(6):e5020. doi: 10.1002/pro.5020.
2
Fragment-based discovery of new potential DNMT1 inhibitors integrating multiple pharmacophore modeling, 3D-QSAR, virtual screening, molecular docking, ADME, and molecular dynamics simulation approaches.基于片段的新型潜在DNMT1抑制剂发现，整合多种药效团建模、3D-QSAR、虚拟筛选、分子对接、ADME和分子动力学模拟方法。
Mol Divers. 2025 Feb;29(1):117-137. doi: 10.1007/s11030-024-10837-5. Epub 2024 Apr 18.
3
DNA methylation profiles in cancer: functions, therapy, and beyond.
癌症中的DNA甲基化图谱：功能、治疗及其他
Cancer Biol Med. 2023 Dec 7;21(2):111-6. doi: 10.20892/j.issn.2095-3941.2023.0403.
4
The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods.2023 年的 ChEMBL 数据库：一个涵盖多种生物活性数据类型和时间段的药物发现平台。
Nucleic Acids Res. 2024 Jan 5;52(D1):D1180-D1192. doi: 10.1093/nar/gkad1004.
5
AlvaBuilder: A Software for De Novo Molecular Design.AlvaBuilder：一款从头设计分子的软件。
J Chem Inf Model. 2024 Apr 8;64(7):2136-2142. doi: 10.1021/acs.jcim.3c00610. Epub 2023 Jul 3.
6
Recent progress in DNA methyltransferase inhibitors as anticancer agents.DNA甲基转移酶抑制剂作为抗癌药物的最新进展。
Front Pharmacol. 2022 Dec 16;13:1072651. doi: 10.3389/fphar.2022.1072651. eCollection 2022.
7
Exploring the druggability of the binding site of aurovertin, an exogenous allosteric inhibitor of FF-ATP synthase.探索金轮菌素（一种FF-ATP合酶的外源性变构抑制剂）结合位点的成药潜力。
Front Pharmacol. 2022 Oct 14;13:1012008. doi: 10.3389/fphar.2022.1012008. eCollection 2022.
8
Computational Design of Inhibitors Targeting the Catalytic β Subunit of FF-ATP Synthase.靶向FF-ATP合酶催化β亚基的抑制剂的计算设计
Antibiotics (Basel). 2022 Apr 22;11(5):557. doi: 10.3390/antibiotics11050557.
9
7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1.基于表观遗传学靶点文库的 7-烷氧基喹唑啉类化合物是 DNA 甲基转移酶 1 的高效和选择性抑制剂。
Molecules. 2022 Apr 30;27(9):2892. doi: 10.3390/molecules27092892.
10
Yes SIR! On the structure-inactivity relationships in drug discovery.是的，先生！关于药物发现中的构效关系。
Drug Discov Today. 2022 Aug;27(8):2353-2362. doi: 10.1016/j.drudis.2022.05.005. Epub 2022 May 11.