期刊论文

Yang, Wen-Chao;Yang, Guang-Fu

英文

European Journal of Medicinal Chemistry

0223-5234

2019

166

22-31

10.1016/j.ejmech.2019.01.032

National Key Research and Development Program of China [2017YFA0505200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21837001, 21672079]; Hubei Province Natural Science FoundationNatural Science Foundation of Hubei Province [2018CFA072]; self-determined research funds of Central China Normal University from colleges' basic research and operation of MOE [CCNU18ZDPY01, CCNU18TS007]

本校为第一且通讯机构

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 d...