Sulfasalazine (599-79-1) is an approved drug with diverse potential applications. Sulfasalzine is a clinically useful agent for the treatment of colitis and ileocolitis.1 It is metabolized by intestinal bacteria to release the anti-inflammatory agent 5-aminosalicylic acid and the antibacterial agent sulfapyridine. It has also been found to be a specific inhibitor of NFκB (IC50 = 500 μM)2, inhibitor of IL-2 production of activated T lymphocytes3 and, TNFα and IL-1 synthesis in macrophages4. Sulfasalazine has more recently been shown to be inhibitor of the system Xc- cystine-glutamate antiporter.5,6 It was able to block cystine uptake causing depletion of glutathione resulting in compromised cellular redox defense and ultimately cessation of tumor growth. It has been studied for the treatment of breast, pancreatic, lymphoma, brain and other cancers.
1) Peppercorn (1984), Sulfasalazine. Pharmacology, clinical use, toxicity, and related drug development; Ann. Intern. Med., 101 377
2) Wahl et al. (1998), Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B; J. Clin. Invest., 101 1163
3) Sheldon et al. (1988), Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocytes Ð clues to its clinical action?; Br. J. Rheumatol., 27 344
4) Fujiwara et al. (1990), Inhibition of proliferation responses and interleukin 2 production by salazosulfapyridine and its metabolites; Jpn. J. Pharmacol., 54 121
5) Chung and Sontheimer (2009), Sulfasalazine inhibits the growth of primary brain tumors in dependent of nuclear factor-κB; J.Neurochem., 110 182
6) Patel et al. (2004), Differentiation of substrate and non-substrate inhibitors of transport system Xc – :an obligate exchanger of L-glutamate and L-cystine; Neuropharmacol., 46 273