Clinical development plan: N-acetyl-l-cysteine (NAC)

✍ Scribed by NCI, DCPC Chemoprevention Branch and Agent Development Committee

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 861 KB
• Volume: 56
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240560907

✦ Synopsis

N-Acetyl-I-cysteine (NAC) is a thiol-containing nucleophile which can detoxify electrophiles and free radicals by direct [ 1 4 ] and enzymatic conjugation [5]. More importantly, the agent also serves as a precursor of intracellular cysteine and glutathione (GSH) [3,6], and enhances the activities of glutathione-S-transferase (GST) [e.g., 7,8], glutathione peroxidase [9,10], GSSG reductase, and NADH: and NAD(P)H:quinone reductase [ill. NAC has antiinflammatory properties [12], and inhibits prostaglandin synthesis [13] and O K activity [7,91. Finally, the agent may promote DNA repair by protecting ADP-ribosyl transferase activity [141. Currently, NAC is an FDA-approved drug primarily used as an aerosolized mucolytic agent (Muco-myst@) in patients with bronchitis [15,16]. Parvolex@, the intravenous form of NAC, was introduced in 1979 as an antidote for liver toxicity resulting from overdose of acetaminophen (Tylenol@) 1171. In addition, administration of NAC has offered protection in chemotherapy [eg., 181 and radiotherapy [19] of cancer patients. Because of its antioxidant and detoxifying properties, as well as apparent safety and lack of major side effects [20,211, the development of NAC as a cancer chemopreventive drug was undertaken.

In preclinical efficacy studies, the chemopreventive activity of NAC was demonstrated in rat colon, intestines and mammary glands, hamster trachea, and mouse lung and bladder. The available studies are adequate to support the development of NAC as a chemopreventive drug. Addi-