Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening

Roland W. Bürli, Huijun Wei, Glen Ernst, Abigail Mariga, Ian M. Hardern, Kara Herlihy, Alan J. Cross, Steven S. Wesolowski, Hongming Chen, Ronald D.G. McKay, Daniel R. Weinberger, Nicholas J. Brandon, James C. Barrow

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)3231-3235
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number19
StatePublished - Oct 15 2018


  • Arsenic methyltransferase
  • As(III) S-adenosylmethionine methyltransferase
  • Methyltransferase
  • Schizophrenia
  • Virtual screening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


Dive into the research topics of 'Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening'. Together they form a unique fingerprint.

Cite this