Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy

doi:10.1021/acsmedchemlett.8b00373

	Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy
	Lu, Xiaoyun 1; Zhang, Tao2,6,7 ; Zhu, Su-Jie 3,4; Xun, Qiuju 5; Tong, Lingjiang 2; Hu, Xianglong 1; Li, Yan 2; Chan, Shingpan 1; Su, Yi 2; Sun, Yiming 2; Chen, Yi 2; Ding, Jian 2; Yun, Cai-Hong 3,4; Xie, Hua 2; Ding, Ke 1
	2018-11
发表期刊	ACS MEDICINAL CHEMISTRY LETTERS (IF:3.5[JCR-2023],3.9[5-Year])
ISSN	1948-5875
卷号	9 期号:11 页码:1123-1127
发表状态	已发表
DOI	10.1021/acsmedchemlett.8b00373
摘要	EGFR(C797S) mutation inducing resistance against third generation EGFR inhibitor drugs is an emerging "unmet clinical need" for nonsmall cell lung cancer patients. The pyrimidopyrimidinone derivative JND3229 was identified as a new highly potent EGFR(C797S) inhibitor with single digit nM potency. It also exhibited good in vitro and in vivo monodrug anticancer efficacy in a xenograft mouse model of BaF3/EGFR(19D/T70M/C797S) cells. A high-resolution X-ray crystallographic structure was also determined to elucidate the interactions between JND3229 and EGFR(T790M/C797S). Our study provides an important structural and chemical basis for future development of new generation EGFR(C797S) inhibitors as anticancer drugs.
关键词	EGFR(C797s) Clinical resistance Fourth-generation nhibitors Monodrug efficacy
收录类别	SCI ; SCIE ; IC
语种	英语
资助项目	Institutes for Drug Discovery and Development of Chinese Academy of Science[CASIMM0120185006]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000449888400011
出版者	AMER CHEMICAL SOC
WOS关键词	CELL LUNG-CANCER ; IMPROVED PHARMACOKINETIC PROPERTIES ; EGFR INHIBITORS ; BIOLOGICAL EVALUATION ; SELECTIVE INHIBITORS ; RECEPTOR INHIBITORS ; C797S RESISTANCE ; DERIVATIVES ; MUTATION ; DESIGN
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/28694
专题	生命科学与技术学院生命科学与技术学院_博士生
通讯作者	Lu, Xiaoyun; Yun, Cai-Hong; Xie, Hua; Ding, Ke
作者单位	1.Jinan Univ, Sch Pharm, Chinese Minist Educ MOE, Int Cooperat Lab Tradit Chinese Med Modernizat &, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China 3.Peking Univ, Hlth Sci Ctr, Dept Biophys, Beijing 100191, Peoples R China 4.Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Beijing 100191, Peoples R China 5.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave, Guangzhou 510530, Guangdong, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 7.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Lu, Xiaoyun,Zhang, Tao,Zhu, Su-Jie,et al. Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy[J]. ACS MEDICINAL CHEMISTRY LETTERS,2018,9(11):1123-1127.
APA	Lu, Xiaoyun.,Zhang, Tao.,Zhu, Su-Jie.,Xun, Qiuju.,Tong, Lingjiang.,...&Ding, Ke.(2018).Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy.ACS MEDICINAL CHEMISTRY LETTERS,9(11),1123-1127.
MLA	Lu, Xiaoyun,et al."Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy".ACS MEDICINAL CHEMISTRY LETTERS 9.11(2018):1123-1127.