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

被引：0

作者：

Prado-Romero, Diana L. ^{[1
]}

Saldivar-Gonzalez, Fernanda I. ^{[1
]}

Lopez-Mata, Ivan ^{[2
,3
]}

Laurel-Garcia, Pedro A. ^{[1
]}

Duran-Vargas, Adrian ^{[4
]}

Garcia-Hernandez, Enrique ^{[4
]}

Sanchez-Cruz, Norberto ^{[3
,5
]}

Medina-Franco, Jose L. ^{[1
]}

机构：

[1] Univ Nacl Autonoma Mexico, Sch Chem, DIFACQUIM Res Grp, Dept Pharm, Ave Univ 3000, Mexico City 04510, Mexico

[2] Univ Juarez Autonoma Tabasco, Div Acad Ciencias Basicas, Carretera Cunduacan Km 1, Jalpa De Mendez 86690, Tabasco, Mexico

[3] Univ Nacl Autonoma Mex, Un Merida, Inst Quim, Carretera Merida-Tetiz Km 4-5, Ucu 97357, Yucatan, Mexico

[4] Univ Nacl Autonoma Mexico, Inst Quim, Mexico City 04510, Mexico

[5] Univ Nacl Autonoma Mex, Inst Invest Matemat Aplicadas & Sistemas, Unidad Merida, Sierra Papacal 97302, Yucatan, Mexico

来源：

BIOMOLECULES | 2024年 / 14卷 / 07期

关键词：

chemoinformatics; drug discovery; docking; epigenetics; epigenetic target profiler; focused libraries; fragments; library design; open-access; DRUG DISCOVERY; BINDING MODES; FORCE-FIELD; OPTIMIZATION; AZACITIDINE; STABILITY; MECHANISM; ACCURACY; SOFTWARE; PROTEINS;

D O I：

10.3390/biom14070775

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：32

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[5] Role for chemoinformatics in structure-based de novo ligand design.
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