Discovery of Coumarin as Microtubule Affinity-Regulating Kinase 4 Inhibitor That Sensitize Hepatocellular Carcinoma to Paclitaxel

doi:10.3389/fchem.2019.00366

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	Discovery of Coumarin as Microtubule Affinity-Regulating Kinase 4 Inhibitor That Sensitize Hepatocellular Carcinoma to Paclitaxel
	Shen, Xianyan 2; Liu, Xuesha 1,2; Wan, Shunli 2; Fan, Xin 1; He, Huaiyu 1; Wei, Rong 1; Pu, Wenchen 1; Peng, Yong 1; Wang, Chun 2
刊名	FRONTIERS IN CHEMISTRY
	2019
卷号	7 页码:366
关键词	MARK4 paclitaxel Hepatocellular carcinoma drug resistance inhibitor
ISSN号	2296-2646
DOI	10.3389/fchem.2019.00366
产权排序	1
文献子类	Article
英文摘要	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.
学科主题	Chemistry
URL标识	查看原文
WOS关键词	BIOLOGICAL EVALUATION ; MARK4 ; TARGET ; PROLIFERATION ; CONDENSATION ; CHECKPOINT ; COMPLEX ; DESIGN ; FAMILY ; GENE
WOS研究方向	Chemistry
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000468900100001
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30992]
专题	国家天然药物工程技术研究中心_天然产物研究
通讯作者	Wang, Chun
作者单位	1.West China Hosp and Coll Life Sci, State Key Lab Biotherapy and Canc Ctr,Sichuan Univ and Collaborat Innovat Ctr Biotherapy, Chengdu, Sichuan, Peoples R China 2.Chinese Acad Sci, Chengdu Inst Biol, Chengdu, Sichuan, Peoples R China;
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.
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,7,366.
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.