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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

DNA (Cytosine-5-)-Methyltransferase 1*/antagonists & inhibitors ; DNA (Cytosine-5-)-Methyltransferase 1*/metabolism ; Enzyme Inhibitors*/chemistry ; Enzyme Inhibitors*/pharmacology ; Drug Design*; Ligands ; Humans ; Small Molecule Libraries/pharmacology ; Small Molecule Libraries/chemistry ; Structure-Activity Relationship

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.

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IN201321 and IG200124 DGAPA, UNAM, Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT)

Keywords: chemoinformatics; docking; drug discovery; epigenetic target profiler; epigenetics; focused libraries; fragments; library design; open-access

0 (Ligands)
EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
0 (Enzyme Inhibitors)
EC 2.1.1.37 (DNMT1 protein, human)
0 (Small Molecule Libraries)

Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240730

20240731

PMC11274800

10.3390/biom14070775

39062489