期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 25, 期 13, 页码 3471-3482出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2017.04.037
关键词
CK2; Fragment-based drug discovery; Kinase inhibition; Fragment linking; Molecular modelling
资金
- Wellcome Trust [090340/Z/09/Z, 107714/Z/15/Z]
- European Research Council under European Union/ERC [279337/DOS]
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council
- Medical Research Council
- Royal Society
- Welcome Trust
- Herchel Smith Funds
- Trinity College, Cambridge
- Cambridge Trust
- Skye Foundation
- Wellcome Trust [107714/Z/15/Z] Funding Source: Wellcome Trust
- EPSRC [EP/J016012/1, EP/P020291/1, EP/K039520/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/K039520/1, EP/J016012/1, EP/P020291/1] Funding Source: researchfish
Recently we reported the discovery of a potent and selective CK2 alpha inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (alpha D pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the alD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors. (C) 2017 Published by Elsevier Ltd.
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