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

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.

Peptidic transition state analogues as PRMT inhibitors.

Protein arginine N-methyltransferases (PRMTs) methylate arginine residues in target proteins using the ubiquitous methyl donor S-adenosyl-l-methionine (AdoMet) as a cofactor. PRMTs play important roles in both healthy and disease states and as such inhibition of PRMTs has gained increasing interest. A primary challenge in the development of PRMT inhibitors is achieving specificity for the PRMT of interest as the active sites are highly conserved for all nine members of the PRMT family.