Recent progress and challenges in screening and characterization of UGT1A1 inhibitors

作     者：Xia Lv Yangliu Xia Moshe Finel Jingjing Wu Guangbo Ge Ling Yang 

作者机构：Institute of Interdisciplinary Medicine Shanghai University of Traditional Chinese Medicine Key Laboratory of Biotechnology and Bioresources Utilization Ministry of Education College of Life ScienceDalian Minzu University Dalian Institute of Chemical Physics Chinese Academy of Sciences Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2019年第9卷第2期

页      面：258-278页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100706[医学-药理学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the NSF of China(81773687,81703606,81573501,81473181) the National Key Research and Development Program of China(2017YFC1700200 and2017YFC1702000) the Fundamental Research Funds for the Central Universities(wd01185) the National S&T Major Projects of China(2017ZX09101004) Program of Shanghai Academic/Technology Research Leader(18XD1403600) the Innovative Entrepreneurship Program of High-level Talents in Dalian(2016RQ025&2017RQ121) the Doctoral Scientific Research Foundation of Liaoning Province,China(20170520059) 

主　　题：UGT1A1 inhibitors Drug/herbdrug interactions Probe substrates High-throughput screening 

摘      要：Uridine-diphosphate glucuronosyltransferase 1 A1(UGT1 A1) is an important conjugative enzyme in mammals that is responsible for the conjugation and detoxification of both endogenous and xenobiotic compounds. Strong inhibition of UGT1 A1 may trigger adverse drug/herb–drug interactions, or result in metabolic disorders of endobiotic metabolism. Therefore, both the US Food and Drug Administration(FDA)and the European Medicines Agency(EMA) have recommended assaying the inhibitory potential of drugs under development on the human UGT1 A1 prior to approval. This review focuses on the significance,progress and challenges in discovery and characterization of UGT1 A1 inhibitors. Recent advances in the development of UGT1 A1 probes and their application for screening UGT1 A1 inhibitors are summarized and discussed in this review for the first time. Furthermore, a long list of UGT1 A1 inhibitors, including information on their inhibition potency, inhibition mode, and affinity, has been prepared and analyzed. Challenges and future directions in this field are highlighted in the final section. The information and knowledge that are presented in this review provide guidance for rational use of drugs/herbs in order to avoid the occurrence of adverse effects via UGT1 A1 inhibition, as well as presenting methods for rapid screening and characterization of UGT1 A1 inhibitors and for facilitating investigations on UGT1 A1–ligand interactions.