Progress on the Computational Development of Epigenetic Modulators of DNA Methyltransferases 3A and 3B

Inhibitors of DNA methyltransferases 3A and 3B (DNMT3A/3B) are promising candidates for the treatment of cancer and other diseases. Selective inhibitors of DNMT3A/3B are also attractive as small-molecule probes. During the past few years has increased significantly the research towards the development of DNMT1 inhibitors. However, there are no reviews of the recent progress in the development of small-molecule inhibitors of DNMT3A/B. Herein we review the status of inhibitors of DNMT3A/3B with emphasis on computational guided approaches. We discuss in a critical manner compound databases containing structure-activity information, crystallographic structures of DNMT3s, structure-guided studies, and virtual ( in silico ) screening coupled with experimental validation that have led to the identification or development of selective inhibitors. Perspectives in the field are also discussed.