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ID: ALA4265895
Journal: Bioorg Med Chem Lett
Title: Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening.
Authors: Bürli RW, Wei H, Ernst G, Mariga A, Hardern IM, Herlihy K, Cross AJ, Wesolowski SS, Chen H, McKay RDG, Weinberger DR, Brandon NJ, Barrow JC.
Abstract: Due to increased interest in As(III) S-adenosylmethionine methyltransferase (AS3MT), a search for chemical probes that can help elucidate function was initiated. A homology model was built based on related enzymes, and virtual screening produced 426 potential hits. Evaluation of these compounds in a functional enzymatic assay revealed several modest inhibitors including an O-substituted 2-amino-3-cyano indole scaffold. Two iterations of near neighbor searches revealed compound 5 as a potent inhibitor of AS3MT with good selectivity over representative methyltransferases DOT1L and NSD2 as well as a representative set of diverse receptors. Compound 5 should prove to be a useful tool to investigate the role of AS3MT and a potential starting point for further optimization.
CiteXplore: 30170942