Author: Khan, J.A.; Forouhar, F.; Tao, X.; Tong, L.
Description: Nicotinamide adenine dinucleotide (NAD(+)) has crucial roles in many cellular processes, both as a coenzyme for redox reactions and as a substrate to donate ADP-ribose units. Enzymes involved in NAD(+) metabolism are attractive targets for drug discovery against a variety of human diseases, including cancer, multiple sclerosis, neurodegeneration and Huntington’s disease. A small-molecule inhibitor of nicotinamide phosphoribosyltransferase, an enzyme in the salvage pathway of NAD(+) biosynthesis, is presently in clinical trials against cancer. An analog of a kynurenine pathway intermediate is efficacious against multiple sclerosis in an animal model. Indoleamine 2,3-dioxygenase plays an important role in immune evasion by cancer cells and other disease processes. Inhibitors against kynurenine 3-hydroxylase can reduce the production of neurotoxic metabolites while increasing the production of neuroprotective compounds. This review summarizes the existing knowledge on NAD(+) metabolic enzymes, with emphasis on their relevance for drug discovery.
Subject Headings: Acrylamides/pharmacology/therapeutic use; Adenosine Diphosphate Ribose/metabolism; Aging/metabolism; Animals; Antineoplastic Agents/pharmacology/therapeutic use; Autoimmune Diseases/drug therapy/metabolism; Clinical Trials, Phase II as Topic; Cyclic ADP-Ribose/physiology; DNA Damage; Drug Design; Enzyme Inhibitors/pharmacology; Humans; Kynurenine/metabolism; Mice; NAD/metabolism/physiology; Neoplasms/drug therapy/metabolism; Neurodegenerative Diseases/drug therapy/metabolism; Neuroprotective Agents/pharmacology/therapeutic use; Piperidines/pharmacology/therapeutic use; Poly Adenosine Diphosphate Ribose/metabolism; Signal Transduction/drug effects/physiology; Sirtuins/antagonists & inhibitors/metabolism; Tryptophan/metabolism
Keywords: Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery
Publication year: 2007
Journal or book title: Expert Opinion on Therapeutic Targets
Volume: 11
Issue: 5
Pages: 695-705
Find the full text :Â https://www.tandfonline.com/doi/abs/10.1517/14728222.11.5.695
Find more like this one (cited by): https://scholar.google.com/scholar?cites=3964701584610459022&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 2510