Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met
	Wang, Lei; Gao, Mingzhao; Tong, Mengya; Xie, Chengying; He, Ye; Fu, Li; Li, Yun; Fu, Haoyu; Lou, Liguang
刊名	AMERICAN JOURNAL OF CANCER RESEARCH
	2018
卷号	8 期号:8 页码:1541-1550
关键词	CT-711 ALK c-Met crizotinib antitumor activity pharmacokinetics
ISSN号	2156-6976
文献子类	Article
英文摘要	Anaplastic lymphoma kinase (ALK) is a validated molecular target for patients harboring ALK rearrangement, which triggers the development of ALK inhibitors. However, the activation of mesenchymal-epithelial transition factor (c-Met) has emerged as a common cause of acquired resistance induced by selective ALK inhibitors. Herein, we report the first preclinical characterization of CT-711, a novel dual inhibitor of ALK and c-Met. CT-711 demonstrates potent inhibitory activity against ALK kinase activity. Moreover, CT-711 profoundly inhibits ALK signal transduction and thereby induces G1 phase arrest and apoptosis, and results in remarkable anti-proliferative activity against ALK-driven cancer cells. Furthermore, CT-711 effectively inhibits c-Met kinase activity and potently overcomes the resistance mediated by c-Met activation. When orally administered to nude mice bearing xenografts, CT-711 exhibits favorable pharmacokinetic properties and robust antitumor activity. It is noteworthy that CT-711 is superior to crizotinib, the first-in-class ALK inhibitor, in the treatment of ALK-driven cancers in various models. The results of the current study provide a solid foundation for the clinical investigation of CT-711 in patients with tumors harboring ALK rearrangement.
资助项目	National Natural Science Foundation of China[81502636] ; Shanghai Science and Technology Committee[14DZ2294100]
WOS关键词	CELL LUNG-CANCER ; ANAPLASTIC LYMPHOMA KINASE ; DRUG-RESISTANCE ; CRIZOTINIB ; ALECTINIB ; POTENT
WOS研究方向	Oncology
语种	英语
出版者	E-CENTURY PUBLISHING CORP
WOS记录号	WOS:000443206500015
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272300]
专题	药理学第一研究室
通讯作者	Lou, Liguang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Lei,Gao, Mingzhao,Tong, Mengya,et al. Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2018,8(8):1541-1550.
APA	Wang, Lei.,Gao, Mingzhao.,Tong, Mengya.,Xie, Chengying.,He, Ye.,...&Lou, Liguang.(2018).Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met.AMERICAN JOURNAL OF CANCER RESEARCH,8(8),1541-1550.
MLA	Wang, Lei,et al."Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met".AMERICAN JOURNAL OF CANCER RESEARCH 8.8(2018):1541-1550.