LLDT-288, a novel triptolide analogue exhibits potent antitumor activity in vitro and in vivo

doi:10.1016/j.biopha.2017.06.041

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	LLDT-288, a novel triptolide analogue exhibits potent antitumor activity in vitro and in vivo
	Xu, Hongtao1,2 ; Fan, Xiaoting1,4 ; Zhang, Guanjun 3; Liu, Xiaoyu1 ; Li, Zhihong1 ; Li, Yuanchao 2; Jiang, Biao1
	2017-09
发表期刊	BIOMEDICINE & PHARMACOTHERAPY (IF:6.9[JCR-2023],6.8[5-Year])
ISSN	0753-3322
EISSN	1950-6007
卷号	93 页码:1004-1009
发表状态	已发表
DOI	10.1016/j.biopha.2017.06.041
摘要	(14S)-14 beta-(1-(2-morpholinoethyl)-1H-indazol-5-ylamino) mthylepitriptolide (LLDT-288) was a novel C14 beta-heterocycle aminomethyl substituent triptolide analogue, which showed comparable cytotoxicity to triptolide. Here we demonstrated that LLDT-288 displayed broad-spectrum, potent antitumor activity, effectively against drug-resistance cancer cells, and induced apoptosis in vitro, but exerted low toxicity. Moreover, it exhibited a remarkable microsomal stability, and showed no inhibitory effects on different cytochrome P450 isoforms. In vivo, orally administration of LLDT-288 exhibits promising efficacy in human prostate (PC-3) xenograft mice model with obviously low toxicity. Further, the in vivo metabolic studies suggested that LLDT-288 was extensively metabolized in rats and mainly excreted in the form of metabolites in the feces. (C) 2017 Published by Elsevier Masson SAS.
关键词	Triptolide Natural products Drug-resistance CYP
收录类别	SCI
语种	英语
资助项目	Open Foundation of the State Key Laboratory of Drug Research, China[SIMM1601KF-05]
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS类目	Medicine, Research & Experimental ; Pharmacology & Pharmacy
WOS记录号	WOS:000407923000109
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS关键词	PANCREATIC-CANCER CELLS ; ANTICANCER ACTIVITY ; TRIPTERYGIUM-WILFORDII ; SIGNALING PATHWAY ; RESISTANCE ; TRIPDIOLIDE ; TRIPTONIDE ; INHIBITION ; ACTIVATION ; APOPTOSIS
原始文献类型	Article
通讯作者	Li, Yuanchao ; Jiang, Biao
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/4509
专题	免疫化学研究所免疫化学研究所_特聘教授组_抗体化学实验室免疫化学研究所_特聘教授组_抗体设计学实验室生命科学与技术学院_硕士生
通讯作者	Li, Yuanchao; Jiang, Biao
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Tianjin Univ Sci & Technol, Coll Chem Engn & Mat Sci, Tianjin 300457, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Xu, Hongtao,Fan, Xiaoting,Zhang, Guanjun,et al. LLDT-288, a novel triptolide analogue exhibits potent antitumor activity in vitro and in vivo[J]. BIOMEDICINE & PHARMACOTHERAPY,2017,93:1004-1009.
APA	Xu, Hongtao.,Fan, Xiaoting.,Zhang, Guanjun.,Liu, Xiaoyu.,Li, Zhihong.,...&Jiang, Biao.(2017).LLDT-288, a novel triptolide analogue exhibits potent antitumor activity in vitro and in vivo.BIOMEDICINE & PHARMACOTHERAPY,93,1004-1009.
MLA	Xu, Hongtao,et al."LLDT-288, a novel triptolide analogue exhibits potent antitumor activity in vitro and in vivo".BIOMEDICINE & PHARMACOTHERAPY 93(2017):1004-1009.