4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target.

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Yang DY

4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target.

Drug News Perspect. 2003 Oct;16(8):493-6.

PubMed ID

14668946 [ View in PubMed

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Abstract

The molecular mechanism for 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) inhibition by nitisinone, a recently approved new drug for the treatment of hereditary tyrosinemia type I, has been satisfactorily explained by its action as an analogue to the substrate 4-hydroxyphenylpyruvate. In addition, a novel induced conformationally restricted 4-HPPD inhibitor, diketonitrile, which serves as a nonclassical bioisostere for rigid cyclic 1,3-diketone derivatives, has been introduced. Further application of the molecular mode of action of nitisinone in rational design of potential inhibitors for alpha-ketoglutarate-coupled dioxygenases is discussed.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nitisinone	4-hydroxyphenylpyruvate dioxygenase	Protein	Humans	Yes	Inhibitor	Details