Ding-Yah Yang
Oct 1, 2003
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Influential Citations
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Journal
Drug news & perspectives
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.