机构：[1]Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China[2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and College of Life Sciences, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China四川大学华西医院
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. Nowadays, pharmacological therapy for HCC is in urgent needs. Paclitaxel is an effective drug against diverse solid tumors, but commonly resisted in HCC patients. We recently have disclosed that microtubule affinity-regulating kinase 4 (MARK4) increases the microtubule dynamics and confers paclitaxel resistance in HCC, suggesting MARK4 as an attractive target to overcome paclitaxel resistance. Herein, we synthesized and identified coumarin derivatives 50 as a novel MARK4 inhibitor. Biological evaluation indicated compound 50 directly interacted with MARK4 and inhibited its activity in vitro, suppressed cell viability and induced apoptosis of HCC cells in a MARK4-dependent manner. Importantly, compound 50 significantly increased the drug response of paclitaxel treatment to HCC cells, providing a promise strategy to HCC treatment and broadening the application of paclitaxel in cancer therapy.
基金：
Chengdu Institute
of Biology, Chinese Academy of Sciences for his kind support
(funded by National Natural Science Foundation of China:
No. 21861142007). This work was also supported by National
Natural Science Foundation of China (No. 81772960 and
81572739 to YP; No. 81702980 to WP), the Key Research and
Development Project of Sichuan Province (No. 19ZDYF2612
to CW), the Sichuan Science and Technology Program (No.
2019JDTD0013 to YP), the Fundamental Research Funds for
the Central Universities (No. 2018SCUH0088 to WP), the
Postdoctoral Science Foundation of Sichuan University (No.
2019SCU12037 to WP) and the 1.3.5 Project for Disciplines
of Excellence (No. ZYJC18030 to YP), West China Hospital,
Sichuan University.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|3 区化学
小类|3 区化学综合
最新[2023]版：
大类|3 区化学
小类|3 区化学：综合
第一作者：
第一作者机构：[1]Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Shen Xianyan,Liu Xuesha,Wan Shunli,et al.Discovery of Coumarin as Microtubule Affinity-Regulating Kinase 4 Inhibitor That Sensitize Hepatocellular Carcinoma to Paclitaxel.[J].Frontiers in chemistry.2019,7:366.doi:10.3389/fchem.2019.00366.
APA：
Shen Xianyan,Liu Xuesha,Wan Shunli,Fan Xin,He Huaiyu...&Wang Chun.(2019).Discovery of Coumarin as Microtubule Affinity-Regulating Kinase 4 Inhibitor That Sensitize Hepatocellular Carcinoma to Paclitaxel..Frontiers in chemistry,7,
MLA：
Shen Xianyan,et al."Discovery of Coumarin as Microtubule Affinity-Regulating Kinase 4 Inhibitor That Sensitize Hepatocellular Carcinoma to Paclitaxel.".Frontiers in chemistry 7.(2019):366
