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

Drug Discov Today. 2021 Nov;26(11):2699-2706. doi: 10.1016/j.drudis.2021.05.011. Epub 2021 May 21.

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.

Keywords: Cancer; Inhibitors; Metabolic disorder; NNMT; Neurodegenerative disease; Nicotinamide; S-adenosyl-l-methionine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*
  • Niacinamide / analogs & derivatives
  • Niacinamide / metabolism
  • Nicotinamide N-Methyltransferase / antagonists & inhibitors
  • Nicotinamide N-Methyltransferase / metabolism*
  • S-Adenosylmethionine / metabolism

Substances

  • Enzyme Inhibitors
  • Niacinamide
  • S-Adenosylmethionine
  • Nicotinamide N-Methyltransferase
  • N(1)-methylnicotinamide