This technology describes a method in which an inhibitor of an arylamine N-acetyl transferase (NAT), a member of a common enzyme family, is administered to a human to inhibit acetylation reactions resulting in production of cytotoxic or carcinogenic compounds in the treated individual. Nearly all drugs are metabolized in the human body by enzymes. Although metabolism generally lowers the toxicity of drugs, the opposite effect is often encountered with NAT. With NAT, the resulting metabolite is more toxic than the parent drug. Administering an inhibitor of NAT with such drugs is believed to result in decreased toxicity to the patient because of reduced exposure to the metabolite. Reduced exposure to the metabolite is believed to be beneficial to patients because the reduction in toxicity results in the maximization of the benefits of the parent drug. Accordingly, this method could be utilized in many therapeutic areas, since drugs which are metabolized by NAT are used in most medical disciplines, including heart disease, infectious diseases, and oncology. The technology also describes the acetylation capacity of NAT's link to human tumors. The acetylation capacity can be reduced by an enzyme inhibitor which may lead to a decrease in human cancer. This concept identifies NAT as a novel target, to expand and improve a general strategy which is currently-emerging, known as "chemoprevention". Finally, the technology describes specific inhibitors of NAT in human hepatocoytes, e.g., para-amino salicylate (PAS) for NAT1 and dichlorphenamide for NAT2, which can be used either in chemoprevention of cancer or in conjunction with a chemotherapeutic which metabolizes NAT, potentially resulting in reduced toxicity to the patient. Since these inhibitors are currently-marketed drugs, clinical development can be accelerated, and pilot studies are already underway.
U.S. Patent No. 6,423,696 issued 2002-07-23
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
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OTT Reference No: E-268-1998/0
Updated: August 10, 2015