4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target.

Ding-Yah Yang

Journal: Drug news & perspectives 2004;16(8):493-6

PMID: 14668946

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.

Address: Department of Chemistry, Tunghai University, Taichung, Taiwan. [email protected]

DOI: 10.1358/dnp.2003.16.8.829347

Link outs

Free resources

Other Literature Sources:

https://www.lens.org/lens/search/patent/list?q=ref...

MeSH Terms: 4-Hydroxyphenylpyruvate Dioxygenase, Cyclohexanones, Drug Design, Enzyme Inhibitors, Forecasting, Isoxazoles, Molecular Structure, Nitriles, Nitrobenzoates, Oxygenases, Sulfones, Tyrosinemias