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  • Title: Hydrophobicity-oriented drug design (HODD) of new human 4-hydroxyphenylpyruvate dioxygenase inhibitors.
    Author: Ndikuryayo F, Kang WM, Wu FX, Yang WC, Yang GF.
    Journal: Eur J Med Chem; 2019 Mar 15; 166():22-31. PubMed ID: 30684868.
    Abstract:
    Involved in the tyrosine degradation pathway, 4-hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for treating type I tyrosinemia. To discover novel HPPD inhibitors, we proposed a hydrophobicity-oriented drug design (HODD) strategy based on the interactions between HPPD and the commercial drug NTBC. Most of the new compounds showed improved activity, compound d23 being the most active candidate (IC50 = 0.047 μM) with about 2-fold more potent than NTBC (IC50 = 0.085 μM). Therefore, compound d23 is a potential drug candidate to treat type I tyrosinemia.
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