title: The role of nitisinone in tyrosine pathway disorders.
abstract: Nitisinone 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC), an effective herbicide, is the licensed treatment for the human condition, hereditary tyrosinaemia type 1 (HT-1). Its mode of action interrupts tyrosine metabolism through inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD). Nitisinone is a remarkable safe drug to use with few side effects reported. Therefore, we propose that it should be investigated as a potential treatment for other disorders of tyrosine metabolism. These include alkaptonuria (AKU), a rare disease resulting is severe, early-onset osteoarthritis. We present a case study from the disease, and attempts to use the drug both off-label and in clinical research through the DevelopAKUre consortium.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK, e.lock@ljmu.ac.uk.
authors.forename: Edward
authors.initials: E
authors.lastname: Lock
authors.forename: Lakshminarayan R
authors.initials: LR
authors.lastname: Ranganath
authors.forename: Oliver
authors.initials: O
authors.lastname: Timmis
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors; D000474:Alkaptonuria / Q000188:drug therapy*; D000818:Animals; D035843:Biomedical Research; D003512:Cyclohexanones / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009579:Nitrobenzoates / Q000627:therapeutic use*; D056687:Off-Label Use; D020176:Tyrosinemias / Q000188:drug therapy*
chemical_list: D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D009579:Nitrobenzoates; D015111:4-Hydroxyphenylpyruvate Dioxygenase; C077073:nitisinone