机构：[1]Department of Medicinal Chemistry, School of Medicine, Nankai University, Tianjin, China[2]State Key Laboratory and Institute of Elemento- Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, China[3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China四川大学华西医院[4]State Key Laboratory of Medicinal Chemical Biology, Tianjin, China[5]2011 Project Collaborative Innovation Center for Biotherapy of Ministry of Education, Tianjin, China
Indoleamine 2,3-dioxygenase 1 (IDO1) activity links to immune escape of cancers. Inhibition of IDO1 provides a new approach for cancer treatment. Most clinical IDO1 drugs show marginal efficacy as single agents. On basis of molecular docking and pharmacophore modelling, a novel inhibitor Roxyl-WL was discovered with a half maximal inhibitory concentration (IC50) value of 1 nM against IDO1 and 10-100-fold increased potent activity compared with IDO1 drugs in clinical trials. Roxyl-WL displayed excellent kinase spectrum selectivity with no activity out of the 337 protein kinases. In vitro, Roxyl-WL effectively augmented the proliferation of T cells and reduced the number of regulatory T cell (Tregs).When administered to melanoma (B16F10) tumor-bearing mice orally, Roxyl-WL significantly suppressed tumor growth and induced immune response.
基金：
the Project of Science and Technology
Assistance in Developing Countries (KY201501006), National
Natural Science Foundation of China (81470354), Natural Science
Foundation of Tianjin (17JCQNJC13500), and the State Key
Laboratory of Medicinal Chemical Biology (2018004).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区医学
小类|2 区药物化学3 区生化与分子生物学
最新[2023]版：
大类|2 区医学
小类|2 区生化与分子生物学2 区药物化学
第一作者：
第一作者机构：[1]Department of Medicinal Chemistry, School of Medicine, Nankai University, Tianjin, China
通讯作者：
通讯机构：[1]Department of Medicinal Chemistry, School of Medicine, Nankai University, Tianjin, China[4]State Key Laboratory of Medicinal Chemical Biology, Tianjin, China[5]2011 Project Collaborative Innovation Center for Biotherapy of Ministry of Education, Tianjin, China[*1]School of Medicine, Nankai University, 94 Weijin Road, Tianjin, China
推荐引用方式(GB/T 7714)：
Xu Guangwei,Wang Tianqi,Li Yongtao,et al.A highly potent and selective inhibitor Roxyl-WL targeting IDO1 promotes immune response against melanoma.[J].Journal of enzyme inhibition and medicinal chemistry.2018,33(1):1089-1094.doi:10.1080/14756366.2018.1471688.
APA：
Xu Guangwei,Wang Tianqi,Li Yongtao,Huang Zhi,Wang Xin...&Xiang Rong.(2018).A highly potent and selective inhibitor Roxyl-WL targeting IDO1 promotes immune response against melanoma..Journal of enzyme inhibition and medicinal chemistry,33,(1)
MLA：
Xu Guangwei,et al."A highly potent and selective inhibitor Roxyl-WL targeting IDO1 promotes immune response against melanoma.".Journal of enzyme inhibition and medicinal chemistry 33..1(2018):1089-1094
