Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
...
PMID:Discovery and development of DNA methyltransferase inhibitors using in silico approaches. 2552 32

DNA methylations are carried out by DNA methyltransferases (DNMTs) that are key enzymes during gene expression. Many chemicals, including pesticides, have shown modulation of epigenetic functions by inhibiting DNMTs. In this work, human DNMTs were evaluated as a potential target for pesticides through virtual screening of 1038 pesticides on DNMT1 (3SWR) and DNMT3A (2QRV). Molecular docking calculations for DNMTs-pesticide complexes were performed using AutoDock Vina. Binding-affinity values and contact patterns were employed as selection criteria of pesticides as virtual hits for DNMTs. The best three DNMT-pesticides complexes selected according to their high absolute affinity values (kcal/mol), for both DNMT1 and DNMT3A, were flocoumafen (-12.5; -9.9), brodifacoum (-12.4; -8.4) and difenacoum (-12.1; -8.7). These chemicals belong to second-generation rodenticides. The most frequent predicted interacting residues for DNMT1-pesticide complexes were Trp1170A, Phe1145A, Asn1578A, Arg1574A and Pro1225A; whereas for DNMT3A those were Arg271B, Lys740A, and Glu303B. These results suggest that rodenticides used for pest control are potential DNMT ligands and therefore, may modulate DNA methylations. This finding has important environmental and clinical implications, as epigenetic pathways are critical in many biochemical processes leading to diseases.
SAR QSAR Environ Res 2019 Dec
PMID:In silico evaluation of pesticides as potential modulators of human DNA methyltransferases. 3159 89