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

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 be...

Descripción completa

Detalles Bibliográficos
Autores principales: Kannt, Aimo, Rajagopal, Sridharan, Hallur, Mahanandeesha S., Swamy, Indu, Kristam, Rajendra, Dhakshinamoorthy, Saravanakumar, Czech, Joerg, Zech, Gernot, Schreuder, Herman, Ruf, Sven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918612/
https://www.ncbi.nlm.nih.gov/pubmed/33668468
http://dx.doi.org/10.3390/molecules26040991
_version_ 1783657963282497536
author Kannt, Aimo
Rajagopal, Sridharan
Hallur, Mahanandeesha S.
Swamy, Indu
Kristam, Rajendra
Dhakshinamoorthy, Saravanakumar
Czech, Joerg
Zech, Gernot
Schreuder, Herman
Ruf, Sven
author_facet Kannt, Aimo
Rajagopal, Sridharan
Hallur, Mahanandeesha S.
Swamy, Indu
Kristam, Rajendra
Dhakshinamoorthy, Saravanakumar
Czech, Joerg
Zech, Gernot
Schreuder, Herman
Ruf, Sven
author_sort Kannt, Aimo
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7918612
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79186122021-03-02 Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders Kannt, Aimo Rajagopal, Sridharan Hallur, Mahanandeesha S. Swamy, Indu Kristam, Rajendra Dhakshinamoorthy, Saravanakumar Czech, Joerg Zech, Gernot Schreuder, Herman Ruf, Sven Molecules Article 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. MDPI 2021-02-13 /pmc/articles/PMC7918612/ /pubmed/33668468 http://dx.doi.org/10.3390/molecules26040991 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kannt, Aimo
Rajagopal, Sridharan
Hallur, Mahanandeesha S.
Swamy, Indu
Kristam, Rajendra
Dhakshinamoorthy, Saravanakumar
Czech, Joerg
Zech, Gernot
Schreuder, Herman
Ruf, Sven
Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders
title Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders
title_full Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders
title_fullStr Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders
title_full_unstemmed Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders
title_short Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders
title_sort novel inhibitors of nicotinamide-n-methyltransferase for the treatment of metabolic disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918612/
https://www.ncbi.nlm.nih.gov/pubmed/33668468
http://dx.doi.org/10.3390/molecules26040991
work_keys_str_mv AT kanntaimo novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT rajagopalsridharan novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT hallurmahanandeeshas novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT swamyindu novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT kristamrajendra novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT dhakshinamoorthysaravanakumar novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT czechjoerg novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT zechgernot novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT schreuderherman novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders
AT rufsven novelinhibitorsofnicotinamidenmethyltransferaseforthetreatmentofmetabolicdisorders

Ejemplares similares