新型人源 4-羟基苯丙酮酸双加氧酶抑制剂的疏水导向药物设计（HODD）。
Hydrophobicity-oriented drug design (HODD) of new human 4-hydroxyphenylpyruvate dioxygenase inhibitors.
机构信息
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, Chemical Biology Center, College of Chemistry, Central China Normal University, Wuhan, 430079, PR China.
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, Chemical Biology Center, College of Chemistry, Central China Normal University, Wuhan, 430079, PR China.
出版信息
Eur J Med Chem. 2019 Mar 15;166:22-31. doi: 10.1016/j.ejmech.2019.01.032. Epub 2019 Jan 14.
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 (IC = 0.047 μM) with about 2-fold more potent than NTBC (IC = 0.085 μM). Therefore, compound d23 is a potential drug candidate to treat type I tyrosinemia.
参与酪氨酸降解途径，4-羟苯丙酮酸双加氧酶（HPPD）是治疗 1 型酪氨酸血症的重要靶点。为了发现新型 HPPD 抑制剂，我们提出了一种基于 HPPD 与商业药物 NTBC 相互作用的疏水性导向药物设计（HODD）策略。大多数新化合物显示出改善的活性，化合物 d23 是最具活性的候选物（IC=0.047μM），比 NTBC（IC=0.085μM）强约 2 倍。因此，化合物 d23 是治疗 1 型酪氨酸血症的潜在药物候选物。
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