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

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2024 Jul 27

PMID 39062489

Authors

Diana L Prado-Romero

Fernanda I Saldivar-Gonzalez

Ivan Lopez-Mata

Pedro A Laurel-Garcia

Adrian Duran-Vargas

Enrique Garcia-Hernandez

Norberto Sanchez-Cruz

Jose L Medina-Franco

Affiliations

Soon will be listed here.

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.

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