For example, 6 (nanaomycin A) (Figure ) is a selective inhibitor of DNMT3B (do not inhibit DNMT1) and reactivates silenced tumor suppressor genes in human cancer cells. Recently, 5 (GSK3685032) (Figure ) was disclosed as the first selective inhibitor of DNMT1 that reduces global methylation, increases expression of target genes, and has antitumor efficacy in acute myeloid leukemia xenograft models. Also, GSK3482364 is a DNM1-selective inhibitor that reduces global methylation and increases HbF expression, offering the potential for use in treating sickle cell disease. Furthermore, dual inhibitors of DNMT and other epigenetic targets such as G9a and histone deacetylases (HDACs) are emerging as part of a current trend to develop multi-epi-target inhibitors and epi-polypharmacology in general. The dual activity profile as available in the literature for epigenetic targets is indicated. Notably, DNMTi have been identified from different sources such as natural products and synthetic small molecule libraries. Medicinal chemistry, structure-and ligand-based virtual screening, and high-throughput screening of general screening libraries are examples of methodologies that have led to the identification of DNMTi. There are other drug discovery approaches that are used to identify DNMTi such as de novo design and screening of focused libraries. In this regard, chemical companies are developing screening libraries focused on the most therapeutically relevant epigenetic targets. The chemical samples of the libraries are commercially available for experiential testing.