Site-specific construction of triptolide-based antibody-drug conjugates

doi:10.1016/j.bmc.2021.116497

	Site-specific construction of triptolide-based antibody-drug conjugates
	Wei, Ding 1,2,3; Mao, Yurong2,3 ; Xu, Zili2,3 ; Chen, Jiakang2 ; Li, Jiusheng 1; Jiang, Biao2 ; Chen, Hongli2
	2021-12-01
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY (IF:3.3[JCR-2023],3.1[5-Year])
ISSN	0968-0896
EISSN	1464-3391
卷号	51
DOI	10.1016/j.bmc.2021.116497
摘要	Antibody-drug conjugates (ADCs) have emerging as efficient agents to target deliver cytotoxic drugs and reduce their off-target side effects. Triptolide has attracted attention to be used in ADC development. Herein, three rationally designed triptolide drug-linkers have been synthesized for use in site-specific construction of ADCs. Carbamates that were supposed to be more stable than carbonates were introduced to attach triptolide to the linkers. PEG and discrete PEG chains were incorporated to improve the hydrophilicity of drug-linkers. The ADCs were finally site-specifically prepared by conjugation of the drug-linkers to trastuzumab through disulfide rebridging approach. The preliminary anti-tumor activities of these ADCs were evaluated and they displayed high potencies against HER2-targeted cancer in vitro and in vivo.
关键词	Antibody-drug conjugates Triptolide Site-specific construction
收录类别	SCIE ; IC
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
WOS记录号	WOS:000722146000002
出版者	PERGAMON-ELSEVIER SCIENCE LTD
原始文献类型	Article
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/133136
专题	物质科学与技术学院_博士生免疫化学研究所_特聘教授组_抗体化学实验室免疫化学研究所_公共科研平台_分析化学平台生命科学与技术学院_硕士生
通讯作者	Li, Jiusheng; Jiang, Biao; Chen, Hongli
作者单位	1.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201210, Peoples R China; 2.ShanghaItech Univ, Shanghai Inst Adv Immunochem Studies, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, 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
推荐引用方式 GB/T 7714	Wei, Ding,Mao, Yurong,Xu, Zili,et al. Site-specific construction of triptolide-based antibody-drug conjugates[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2021,51.
APA	Wei, Ding.,Mao, Yurong.,Xu, Zili.,Chen, Jiakang.,Li, Jiusheng.,...&Chen, Hongli.(2021).Site-specific construction of triptolide-based antibody-drug conjugates.BIOORGANIC & MEDICINAL CHEMISTRY,51.
MLA	Wei, Ding,et al."Site-specific construction of triptolide-based antibody-drug conjugates".BIOORGANIC & MEDICINAL CHEMISTRY 51(2021).