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6H-Indolo-[2,3-b]-quinoxaline derivatives as promising bifunctional SHP1 inhibitors

文献类型：期刊论文

作者Zhang, Chun6; Dong, Yi-Xin6; Gao, Li-Xin6; Gan, Suya6; Gao, Wenran5; Li, Jia3,4; Xiang, Da-Jun2; Wang, Xin1; Zhou, Yu-Bo3,4; Wang, Wen-Long6
刊名ORGANIC & BIOMOLECULAR CHEMISTRY
出版日期2024-12-17
页码12
ISSN号1477-0520
DOI10.1039/d4ob01492h
通讯作者Xiang, Da-Jun(xiangdjxshospital@yeah.net) ; Wang, Xin(wx@henu.edu.cn) ; Zhou, Yu-Bo(ybzhou@simm.ac.cn) ; Wang, Wen-Long(wenlongwang@jiangnan.edu.cn)
英文摘要Dysfunction in the SHP1 enzyme can cause cancers and many diseases, so it is of great significance to develop novel small molecule SHP1 inhibitors. Through continuous monitoring of metabolic and targeted processes of SHP1 inhibitors in real-time, we can evaluate the effectiveness and toxicity of the inhibitors, further optimize drug design, and explore SHP1 biology. Indoloquinoxaline is an important class of N-containing heterocycle, which has been studied and applied in the pharmacological field and in optoelectronic materials. In this work, the potential Src homology 2 domain-containing phosphatase 1 (SHP1) inhibitor 5a was developed with the help of the structural fusion and scaffold hop of a fluorophore, 6H-indolo-[2,3-b]-quinoxaline, and a bio-active skeleton, thieno[2,3-b]quinoline-procaine. Compound 5a selectively inhibited the SHP1PTP enzyme abilities (IC50 = 2.34 +/- 0.06 mu M), exhibited a significant fluorescence response (P = 0.007) in response to SHP1PTP activity, and emitted strong blue/green fluorescence in MDA-MB-231 cells. Furthermore, compound 5a showed irreversible binding with SHP1PTP in simulations and dialysis experiments. Altogether, compound 5a serves as a bifunctional SHP1 inhibitor, combining imaging and therapeutic functionalities, enhancing our understanding of SHP1 biological mechanisms, and positively impacting novel drug development.
WOS关键词OPTOELECTROCHEMICAL PROPERTIES ; INDOLOQUINOXALINE ; RELEVANT
资助项目National Natural Science Foundation of China[22277043] ; National Natural Science Foundation of China[21772068] ; National Natural Science Foundation of China[JUSRP121065] ; Fundamental Research Funds for the Central Universities[JSSCBS20210848] ; High Level Personnel Project of Jiangsu Province[BK20241605] ; Natural Science Foundation of Jiangsu Province ; BioDuro-Sundia in Wuxi and high-performance computing cluster platform of the School of Biotechnology in Jiangnan University
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001387326800001
出版者ROYAL SOC CHEMISTRY
源URL[http://119.78.100.183/handle/2S10ELR8/315303]  
专题中国科学院上海药物研究所
通讯作者Xiang, Da-Jun; Wang, Xin; Zhou, Yu-Bo; Wang, Wen-Long
作者单位1.Henan Univ, Henan Macquarie Univ Joint Ctr Biomed Innovat, Sch Life Sci, Kaifeng 475004, Henan, Peoples R China
2.Xishan Peoples Hosp Wuxi City, Wuxi 214105, Jiangsu, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China
4.Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.Nanjing Forestry Univ, Coll Mat Sci & Engn, Coinnovat Ctr Efficient Proc & Utilizat Forest Res, Joint Int Res Lab Biomass Energy & Mat, Nanjing 210037, Peoples R China
6.Jiangnan Univ, Sch Life Sci & Hlth Engn, Wuxi 214122, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Chun,Dong, Yi-Xin,Gao, Li-Xin,et al. 6H-Indolo-[2,3-b]-quinoxaline derivatives as promising bifunctional SHP1 inhibitors[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2024:12.
APA Zhang, Chun.,Dong, Yi-Xin.,Gao, Li-Xin.,Gan, Suya.,Gao, Wenran.,...&Wang, Wen-Long.(2024).6H-Indolo-[2,3-b]-quinoxaline derivatives as promising bifunctional SHP1 inhibitors.ORGANIC & BIOMOLECULAR CHEMISTRY,12.
MLA Zhang, Chun,et al."6H-Indolo-[2,3-b]-quinoxaline derivatives as promising bifunctional SHP1 inhibitors".ORGANIC & BIOMOLECULAR CHEMISTRY (2024):12.

入库方式： OAI收割

来源：上海药物研究所

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