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Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders |
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| Authors: | Aimo Kannt Sridharan Rajagopal Mahanandeesha S Hallur Indu Swamy Rajendra Kristam Saravanakumar Dhakshinamoorthy Joerg Czech Gernot Zech Herman Schreuder Sven Ruf |
| Institution: | 1.Fraunhofer Institute for Translational Medicine and Pharmacology-ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany;2.Jubilant Biosys Limited, #96, Industrial Suburb, 2nd Stage Yeshwanthpur, Bangalore 560022, India; (S.R.); (M.S.H.); (I.S.); (R.K.); (S.D.);3.Sanofi-Aventis Deutschland Gmbh, Industriepark Hoechst, 65926 Frankfurt am Main, Germany; (J.C.); (G.Z.); (H.S.) |
| Abstract: | 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. |
| Keywords: | nicotinamide-N-methyltransferase small molecule inhibitor nicotinamide metabolic disease X-ray |