title: Discovery and development of DNA methyltransferase inhibitors using in silico approaches.
abstract: Multiple strategies have evolved during the past few years to advance epigenetic compounds targeting DNA methyltransferases (DNMTs). Significant progress has been made in HTS, lead optimization and determination of 3D structures of DNMTs. In light of the emerging concept of epi-informatics, computational approaches are employed to accelerate the development of DNMT inhibitors helping to screen chemical databases, mine the DNMT-relevant chemical space, uncover SAR and design focused libraries. Computational methods also synergize with natural-product-based drug discovery and drug repurposing. Herein, we survey the latest developments of in silico approaches to advance epigenetic drug and probe discovery targeting DNMTs.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico. Electronic address: medinajl@unam.mx.
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.affiliation: Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Oscar
authors.initials: O
authors.lastname: Méndez-Lucio
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Av. San Fernando 22, Mexico City 14080, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Dueñas-González
authors.affiliation: Life Science Research Institute, Daewoong Pharmaceutical Co. Ltd., 72 Dugye-Ro, Pogok-Eup, Gyeonggi-do 449-814, Republic of Korea.
authors.forename: Jakyung
authors.initials: J
authors.lastname: Yoo
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D017076:Computer-Aided Design; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D057225:Data Mining; D062126:Databases, Chemical; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D015254:DNA Modification Methylases