Molecules (Feb 2021)

Novel Inhibitors of Nicotinamide-<i>N</i>-Methyltransferase for the Treatment of Metabolic Disorders

  • Aimo Kannt,
  • Sridharan Rajagopal,
  • Mahanandeesha S. Hallur,
  • Indu Swamy,
  • Rajendra Kristam,
  • Saravanakumar Dhakshinamoorthy,
  • Joerg Czech,
  • Gernot Zech,
  • Herman Schreuder,
  • Sven Ruf

DOI
https://doi.org/10.3390/molecules26040991
Journal volume & issue
Vol. 26, no. 4
p. 991

Abstract

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Nicotinamide-N-methyltransferase (NNMT) is a cytosolic enzyme catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to nicotinamide (Nam). It is expressed in many tissues including the liver, adipose tissue, and skeletal muscle. Its expression in several cancer cell lines has been widely discussed in the literature, and recent work established a link between NNMT expression and metabolic diseases. Here we describe our approach to identify potent small molecule inhibitors of NNMT featuring different binding modes as elucidated by X-ray crystallographic studies.

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