期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 26, 期 17, 页码 4330-4333出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2016.07.031
关键词
Indoleamine 2,3-dioxygenase; Cancer immunotherapy; Molecular modeling; Cellular assays; Tryptophan metabolism
资金
- Flow Cytometry Facility at the Ludwig Cancer Research of the University of Lausanne
- European FP7 grant PANACREAS
- Fondation Solidar-Immun
Indoleamine 2,3-dioxygenase 2 (IDO2) is a potential therapeutic target for the treatment of diseases that involve immune escape such as cancer. In contrast to IDO1, only a very limited number of inhibitors have been described for IDO2 due to inherent difficulties in expressing and purifying a functionally active, soluble form of the enzyme. Starting from our previously discovered highly efficient 4-aryl-1,2,3-triazole IDO1 inhibitor scaffold, we used computational structure-based methods to design inhibitors of IDO2 which we then tested in cellular assays. Our approach yielded low molecular weight inhibitors of IDO2, the most active displaying an IC50 value of 51 mu M for mIDO2, and twofold selectivity over hIDO1. These compounds could be useful as molecular probes to investigate the biological role of IDO2, and could inspire the design of new IDO2 inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据