文献类型：期刊文献

英文题名：CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors

作者：Xi, Meiyang[1];Chen, Tingkai[2];Wu, Chunlei[1];Gao, Xiaozhong[1];Wu, Yonghua[1];Luo, Xiang[1];Du, Kui[1];Yu, Lemao[1];Cai, Tao[1];Shen, Runpu[1];Sun, Haopeng[2]

机构：[1]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing 312000, Peoples R China;[2]China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China

年份：2019

卷号：164

起止页码：77

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:000458221400006)、、Scopus(收录号：2-s2.0-85059013301)、WOS

基金：The authors greatly acknowledge the support from the Youth Fund of Shaoxing University (No. 20175022) and the grants of National Natural Science Foundation of China (No. 81573281, 81602949). We declare no other conflicts of interest.

语种：英文

外文关键词：Cancer; Overexpression; CDK8 inhibitors; Selectivity

外文摘要：Cyclin-dependent kinases 8 (CDK8) regulates transcriptional process via associating with the mediator complex or phosphorylating transcription factors (TF). Overexpression of CDK8 has been observed in various cancers. It mediates aberrant activation of Wnt/beta-catenin signaling pathway, which is initially recognized and best studied in colorectal cancer (CRC). CDK8 acts as an oncogene and represents a potential target for developing novel CDK8 inhibitors in cancer therapeutics. However, other study has revealed its contrary role. The function of CDK8 is context dependent. Even so, a variety of potent and selective CDK8 inhibitors have been discovered after crystal structures were resolved in two states (active or inactive). In this review, we summarize co-crystal structures, biological mechanisms, dysregulation in cancers and recent progress in the field of CDK8 inhibitors, trying to offer an outlook of CDK8 inhibitors in cancer therapy in future. (C) 2018 Elsevier Masson SAS. All rights reserved.