text: The enzymes that make and use NAD and NADH are important in both pharmacology and the research into future treatments for disease. Drug design and drug development exploits NAD in three ways: as a direct target of drugs, by designing enzyme inhibitors or activators based on its structure that change the activity of NAD-dependent enzymes, and by trying to inhibit NAD biosynthesis.
  Because cancer cells utilize increased glycolysis, and because NAD enhances glycolysis, nicotinamide phosphoribosyltransferase (NAD salvage pathway) is often amplified in cancer cells.
  It has been studied for its potential use in the therapy of neurodegenerative diseases such as Alzheimers and Parkinsons disease as well as multiple sclerosis. A placebo-controlled clinical trial of NADH (which excluded NADH precursors) in people with Parkinson's failed to show any effect.
  NAD is also a direct target of the drug isoniazid, which is used in the treatment of tuberculosis, an infection caused by Mycobacterium tuberculosis. Isoniazid is a prodrug and once it has entered the bacteria, it is activated by a peroxidase enzyme, which oxidizes the compound into a free radical form. This radical then reacts with NADH, to produce adducts that are very potent inhibitors of the enzymes enoyl-acyl carrier protein reductase, and dihydrofolate reductase.
  Since many oxidoreductases use NAD and NADH as substrates, and bind them using a highly conserved structural motif, the idea that inhibitors based on NAD could be specific to one enzyme is surprising. However, this can be possible: for example, inhibitors based on the compounds mycophenolic acid and tiazofurin inhibit IMP dehydrogenase at the NAD binding site. Because of the importance of this enzyme in purine metabolism, these compounds may be useful as anti-cancer, anti-viral, or immunosuppressive drugs. Other drugs are not enzyme inhibitors, but instead activate enzymes involved in NAD metabolism. Sirtuins are a particularly interesting target for such drugs, since activation of these NAD-dependent deacetylases extends lifespan in some animal models. Compounds such as resveratrol increase the activity of these enzymes, which may be important in their ability to delay aging in both vertebrate, and invertebrate model organisms. In one experiment, mice given NAD for one week had improved nuclear-mitochrondrial communication.
  Because of the differences in the metabolic pathways of NAD biosynthesis between organisms, such as between bacteria and humans, this area of metabolism is a promising area for the development of new antibiotics. For example, the enzyme nicotinamidase, which converts nicotinamide to nicotinic acid, is a target for drug design, as this enzyme is absent in humans but present in yeast and bacteria.
  In bacteriology, NAD, sometimes referred to factor V, is used as a supplement to culture media for some fastidious bacteria.