Design, synthesis and biological evaluation of 2-aminopyridine derivatives as USP7 inhibitors

doi:10.1016/j.bioorg.2022.106128

	Design, synthesis and biological evaluation of 2-aminopyridine derivatives as USP7 inhibitors
	Xu, Xiaoming 1; Wang, Mingchen2,3,4 ; Xu, Hailong 1; Liu, Na 1; Chen, Kaixian2,3,4 ; Luo, Cheng 2,3,4,5; Chen, Shijie 2,4; Chen, Hua 1
	2022-12-01
发表期刊	BIOORGANIC CHEMISTRY (IF:4.5[JCR-2023],4.7[5-Year])
ISSN	0045-2068
EISSN	1090-2120
卷号	129
发表状态	已发表
DOI	10.1016/j.bioorg.2022.106128
摘要	A series of novel 2-aminopyridine derivatives 1–26 have been designed and synthesized by structural modifications on a lead USP7 inhibitor, GNE6640. All the compounds were evaluated for their USP7 inhibitory activities. The results showed that most of the compounds have good USP7 inhibitory activities at the concentration of 50 μM. Among them, compounds 7, 14 and 21 are the most potential ones from each category with the IC values of 7.6 ± 0.1 μM, 17.0 ± 0.2 μM and 11.6 ± 0.5 μM, respectively. Compounds 7 and 21 expressed significant binding interactions with USP7 by surface plasmon resonance (SPR)-based binding assay, but both of them presented moderate antiproliferative activities against HCT116 cells. They could effectively promote MDM2 degradation, p53 stabilization and p21 gene expression in the western blot analysis.
关键词	Aminopyridine Colorectal carcinoma MDM2 P53 and p21 Suzuki coupling reaction USP7 inhibitors
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Natural Science Interdisciplinary Research Program of Hebei University[DXK201903] ; Science and Technology Commission of Shanghai Municipality["21ZR1474700","19XD1404700"] ; Youth Innovation Promotion Association of CAS[2022279]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS记录号	WOS:000911773700003
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
Scopus 记录号	2-s2.0-85138808641
来源库	Scopus
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/238182
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_陈凯先组
通讯作者	Chen, Shijie; Chen, Hua
作者单位	1.Hebei Univ, Coll Chem & Environm Sci, Key Lab Chem Biol Hebei Prov, Baoding 071002, Peoples R China 2.Chinese Acad Sci, Ctr Chem Biol, Drug Discovery & Design Ctr, Shanghai Inst Mat Medial,State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
推荐引用方式 GB/T 7714	Xu, Xiaoming,Wang, Mingchen,Xu, Hailong,et al. Design, synthesis and biological evaluation of 2-aminopyridine derivatives as USP7 inhibitors[J]. BIOORGANIC CHEMISTRY,2022,129.
APA	Xu, Xiaoming.,Wang, Mingchen.,Xu, Hailong.,Liu, Na.,Chen, Kaixian.,...&Chen, Hua.(2022).Design, synthesis and biological evaluation of 2-aminopyridine derivatives as USP7 inhibitors.BIOORGANIC CHEMISTRY,129.
MLA	Xu, Xiaoming,et al."Design, synthesis and biological evaluation of 2-aminopyridine derivatives as USP7 inhibitors".BIOORGANIC CHEMISTRY 129(2022).