Research Information System
Orphan Drugs: Research and Reviews, vol.7, pp.25-35, 2017 (Scopus)
© 2017 Aktuglu-Zeybek and Zubarioglu.Nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]cyclohexane-1,3-dione), an effective triketone herbicide, is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the tyrosine catabolic pathway. Since 1992, the drug has become an effective pharmacological treatment for hereditary tyrosinemia type 1 (HT1). Nitisinone can prevent the development of liver disease, reverse and prevent the renal tubular dysfunction, severe neurological crisis and cardiomyopathy and significantly reduce the risk of developing hepatocellular carcinoma in HT1 patients. Its mode of action, with few side effects reported, make the drug a potential candidate for the treatment of other disorders of tyrosine metabolism, including alkaptonuria, with successful reduction in homogentisic acid production to prevent long-term complications. Nitisinone could also be a promising agent in the treatment of tumors with active tyrosine metabolic pathways. In this review, we discuss the effects of nitisinone for various tyrosine pathway disorders.