title: NAD+ Kinase as a Therapeutic Target in Cancer.
abstract: NAD+kinase (NADK) catalyzes the phosphorylation of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide phosphate (NADP+) using ATP as the phosphate donor. NADP+is then reduced to NADPH by dehydrogenases, in particular glucose-6-phosphate dehydrogenase and the malic enzymes. NADPH functions as an important cofactor in a variety of metabolic and biosynthetic pathways. The demand for NADPH is particularly high in proliferating cancer cells, where it acts as a cofactor for the synthesis of nucleotides, proteins, and fatty acids. Moreover, NADPH is essential for the neutralization of the dangerously high levels of reactive oxygen species (ROS) generated by increased metabolic activity. Given its key role in metabolism and regulation of ROS, it is not surprising that several recent studies, including in vitro and in vivo assays of tumor growth and querying of patient samples, have identified NADK as a potential therapeutic target for the treatment of cancer. In this review, we will discuss the experimental evidence justifying further exploration of NADK as a clinically relevant drug target and describe our studies with a lead compound, thionicotinamide, an NADK inhibitor prodrug. Clin Cancer Res; 22(21); 5189-95. ©2016 AACR.
authors: Departments of Medicine and Pharmacology, Rutgers Robert Wood Johnson Medical School, the Rutgers Cancer Institute of New Jersey, and the Rutgers Graduate School of Biomedical Sciences, New Brunswick, New Jersey.
authors: Philip M
authors: PM
authors: Tedeschi
authors: Departments of Medicine and Pharmacology, Rutgers Robert Wood Johnson Medical School, the Rutgers Cancer Institute of New Jersey, and the Rutgers Graduate School of Biomedical Sciences, New Brunswick, New Jersey.
authors: Nitu
authors: N
authors: Bansal
authors: Departments of Medicine and Pharmacology, Rutgers Robert Wood Johnson Medical School, the Rutgers Cancer Institute of New Jersey, and the Rutgers Graduate School of Biomedical Sciences, New Brunswick, New Jersey.
authors: John E
authors: JE
authors: Kerrigan
authors: Departments of Medicine and Pharmacology, Rutgers Robert Wood Johnson Medical School, the Rutgers Cancer Institute of New Jersey, and the Rutgers Graduate School of Biomedical Sciences, New Brunswick, New Jersey.
authors: Emine E
authors: EE
authors: Abali
authors: Departments of Medicine and Pharmacology, Rutgers Robert Wood Johnson Medical School, the Rutgers Cancer Institute of New Jersey, and the Rutgers Graduate School of Biomedical Sciences, New Brunswick, New Jersey. bertinoj@cinj.rutgers.edu kathleen.scotto@rutgers.edu.
authors: Kathleen W
authors: KW
authors: Scotto
authors: Departments of Medicine and Pharmacology, Rutgers Robert Wood Johnson Medical School, the Rutgers Cancer Institute of New Jersey, and the Rutgers Graduate School of Biomedical Sciences, New Brunswick, New Jersey. bertinoj@cinj.rutgers.edu kathleen.scotto@rutgers.edu.
authors: Joseph R
authors: JR
authors: Bertino
mesh_terms: D000818:Animals; D006801:Humans; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009243:NAD; D009249:NADP; D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase