BM6, a new semi-synthetic Vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles

doi:10.4161/cbt.6.5.4006

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

	BM6, a new semi-synthetic Vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles
	Li, Weihong ; Shao, Yong ; Hu, Lihong ; Zhang, Xiongwen ; Chen, Yi; Tong, Linjiang ; Li, Chuan; Shen, Xu; Ding, Jian
刊名	CANCER BIOLOGY & THERAPY
	2007-05
卷号	6 期号:5 页码:787-794
关键词	BM6 Vinca alkaloids anti-tumor mitotic arrest cytoskeleton tubulin binding pharmacokinetics
ISSN号	1538-4047
DOI	10.4161/cbt.6.5.4006
文献子类	Article
英文摘要	The aim of this study was to evaluate the anti-tumor activities and to establish the mechanism of the action of 3-decarboxyl-acetyloxylmethyl-anhydrovinblastine (BM6), a new semi-synthetic Vinca alkaloid, in an effort towards finding the favorable therapeutics of Vinca alkaloid derivatives. BM6 was characterized by its superior in vivo activity to vinorelbine in preclinical tumor models, though BM6 exerted in vitro cytotoxic activity against a wide spectrum of tumor cell lines with IC50 values generally 10-fold higher than the classic Vinca alkaloids. Of note, BM6 displayed more potent cytotoxic activity against multidrug-resistant sublines. We further found that BM6 shared the mitotic arresting and tubulin-interacting properties comparable with other Vinca alkaloids. BM6 also induced significant cell cycle arrested in mitosis and cytoskeleton disruption via interacting with the Vinca binding site on tubulin. Encouragingly, the features in term of its higher tubulin binding affinities and better pharmacokinetic profiles highlight BM6 distinct from other Vinca alkaloids, which help provide more data for exploiting new semi-synthetic Vinca alkaloids.
WOS关键词	PERFORMANCE LIQUID-CHROMATOGRAPHY ; CELL-PROLIFERATION ; MULTIDRUG-RESISTANCE ; MICROTUBULE DYNAMICS ; CLINICAL DEVELOPMENT ; VINFLUNINE ; CANCER ; SITE ; COLCHICINE ; MECHANISM
WOS研究方向	Oncology
语种	英语
出版者	TAYLOR & FRANCIS INC
WOS记录号	WOS:000248259900036
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273268]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zhang, Xiongwen
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Weihong,Shao, Yong,Hu, Lihong,et al. BM6, a new semi-synthetic Vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles[J]. CANCER BIOLOGY & THERAPY,2007,6(5):787-794.
APA	Li, Weihong.,Shao, Yong.,Hu, Lihong.,Zhang, Xiongwen.,Chen, Yi.,...&Ding, Jian.(2007).BM6, a new semi-synthetic Vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles.CANCER BIOLOGY & THERAPY,6(5),787-794.
MLA	Li, Weihong,et al."BM6, a new semi-synthetic Vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles".CANCER BIOLOGY & THERAPY 6.5(2007):787-794.