南方科技大学知识苑(SUSTech KC): Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC)

题名	Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC)
作者	Zhang, Jianchao1 ; Chen, Xiao 1 ; Chen, Congli 2; Li, Fengming 3 ; Song, Xiaoxiao1 ; Liu, Chaowei 1 ; Liao, Kefan1 ; Su, Ming-Yuan1,4,5 ; Tan, Chris Soon Heng3 ; Fang, Lijing 2; Rao, Hai 1,4
通讯作者	Zhang, Jianchao; Fang, Lijing; Rao, Hai
发表日期	2024-08-01
DOI	10.1021/acs.jmedchem.4c00208
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY 影响因子和分区
ISSN	0022-2623
EISSN	1520-4804
摘要	Proteolysis-targeting chimeras (PROTACs) selectively eliminate detrimental proteins by exploiting the ubiquitin-proteasome system (UPS), representing a promising therapeutic strategy against various diseases. Effective adaptations of degradation signal sequences and E3 ligases for PROTACs remain limited. Here, we employed three amino acids & horbar;Gly, Pro, and Lys & horbar;as the ligand to recruit the corresponding E3 ligases: CRL2(ZYG11B/ZER1), GID4, and UBRs, to degrade EML4-ALK and mutant EGFR, two oncogenic drivers in NSCLC. We found that the extent of EML4-ALK and EGFR reduction can be easily fine-tuned by using different degradation signals. These amino acid-based PROTACs, termed AATacs, hindered proliferation and induced cell cycle arrest and apoptosis of NSCLC cells in vitro. Compared to other PROTACs, AATacs are small, interchangeable but with different degradation efficiency. Our study further expands the repertoire of E3 ligases and their ligands for PROTAC application, improving the versatility and utility of targeted protein degradation for therapeutic purposes.
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	第一 ; 通讯
资助项目	National Key Research and Development Program[2021YFA0909300] ; National Natural Science Foundation of China[82170159] ; Shenzhen Fundamental Research Program["JCYJ20220818100412028","JCYJ20210324105007019","JCYJ20220818101404010"] ; Key Talent Program of Guangdong[2021CX02Y084] ; High level of special funds[G03050K003] ; Medical Research Innovation Project[G030410001] ; Natural Science Foundation of Guangdong Province[2023A1515011765]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:001287536100001
出版者	AMER CHEMICAL SOC
ESI学科分类	CHEMISTRY
来源库	Web of Science
引用统计
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/803299
专题	南方科技大学医学院_生物化学系南方科技大学南方科技大学医学院理学院_化学系
作者单位	1.Southern Univ Sci & Technol, Sch Med, Dept Biochem, Shenzhen 518055, Peoples R China 2.Chinese Acad Sci, Guangdong Key Lab Nanomed, CAS Key Lab Biomed Imaging Sci & Syst, CAS HK Joint Lab Biomat,Inst Biomed & Biotechnol,S, Shenzhen 518055, Peoples R China 3.Southern Univ Sci & Technol, Dept Chem, Shenzhen 518055, Peoples R China 4.Southern Univ Sci & Technol, Key Univ Lab Metab & Hlth Guangdong, Shenzhen 518055, Peoples R China 5.Southern Univ Sci & Technol, Inst Biol Electron Microscopy, Shenzhen 518055, Peoples R China
第一作者单位	生物化学系; 南方科技大学医学院
通讯作者单位	生物化学系; 南方科技大学医学院; 南方科技大学
第一作者的第一单位	生物化学系; 南方科技大学医学院
推荐引用方式 GB/T 7714	Zhang, Jianchao,Chen, Xiao,Chen, Congli,et al. Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC)[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024.
APA	Zhang, Jianchao.,Chen, Xiao.,Chen, Congli.,Li, Fengming.,Song, Xiaoxiao.,...&Rao, Hai.(2024).Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC).JOURNAL OF MEDICINAL CHEMISTRY.
MLA	Zhang, Jianchao,et al."Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC)".JOURNAL OF MEDICINAL CHEMISTRY (2024).