Abstract
Bisubstrate strategies address the lack of specificity encountered with S-adenosyl-L-methionine (SAM) analogues targeting methyltransferases (MTases). Specifically, a bisubstrate inhibitor mimics the transition state complex associating a substrate and the SAM methyl group donor to a particular methyltransferase. These potential inhibitors contain both parts of the substrate and the methyl group donor. In this review, bisubstrate inhibitors of several MTases including DNA, RNA, protein, catechol or nicotinamide MTases are discussed in order to evaluate the interest of these promising molecules for the development of selective therapeutics against cancers, neuropsychiatric disorders and viral infections.