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Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders.


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.

SUBMITTER: Kannt A 

PROVIDER: S-EPMC7918612 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Kannt Aimo A   Rajagopal Sridharan S   Hallur Mahanandeesha S MS   Swamy Indu I   Kristam Rajendra R   Dhakshinamoorthy Saravanakumar S   Czech Joerg J   Zech Gernot G   Schreuder Herman H   Ruf Sven S  

Molecules (Basel, Switzerland) 20210213 4


Nicotinamide-<i>N</i>-methyltransferase (NNMT) is a cytosolic enzyme catalyzing the transfer of a methyl group from <i>S</i>-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  ...[more]

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