Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target.

Yongzhi Gao, Nathaniel I Martin, Matthijs J van Haren

Journal: Drug discovery today 2022;26(11):2699-2706

PMID: 34029690

Free Full Text on Elsevier Science View on PubMed

Abstract

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors.

Address: Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, the Netherlands.; Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, the Netherlands. Electronic address: [email protected].; Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, the Netherlands. Electronic address: [email protected].

DOI: 10.1016/j.drudis.2021.05.011

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MeSH Terms: Enzyme Inhibitors, Humans, Metabolic Diseases, Neoplasms, Neurodegenerative Diseases, Niacinamide, Nicotinamide N-Methyltransferase, S-Adenosylmethionine