作者：
Xianglong Hu;Qiuju Xun;Tao Zhang;Su-Jie Zhu;Qian Li;Linjiang Tong;Mengzhen Lai;Tao Huang;Cai-Hong Yun;Hua Xie;Ke Ding;Xiaoyun Lu;
机构：
International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE),School of Pharmacy,Jinan University;Division of Antitumor Pharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences;Institute for Translational Medicine,College of Medicine,Qingdao University;Department of Biochemistry and Biophysics,Institute of Systems Biomedicine,School of Basic Medical Sciences,Peking University Health Science Center;
中文摘要：
Extensive structure-activity relationships(SARs) study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido [4,5-d]pyrimidine privileged scaffold as EGFRC797 S inhibitors.One of the most potent compound 6 i potently suppressed EGFR~(L858 R/T790 M/C797 S) kinase with an IC_(50) value of 3.1 nmol/L,and inhibited the proliferation of BaF3 cells harboring EGFR~(L858 R/T790 M/C797 S) and EGFR~(19 D/T790 M/C797 S) mutants with IC_(50) values of 290 nmol/L and 316 nmol/L,respectively.Further,6 i dose-dependently induced suppression of the phosphorylation of EGFR~(L858 R/T790 M/C797 S) and EGFR~(19 D/T790 M/C797 S) in BaF3 cells.Compound 6 i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer(NSCLC) patients.
英文篇名：
2-Oxo-3,4-dihydropyrimido[4,5-d] pyrimidines as new reversible inhibitors of EGFR C797S(Cys797 to Ser797)mutant
英文作者：
Xianglong Hu;Qiuju Xun;Tao Zhang;Su-Jie Zhu;Qian Li;Linjiang Tong;Mengzhen Lai;Tao Huang;Cai-Hong Yun;Hua Xie;Ke Ding;Xiaoyun Lu;International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE),School of Pharmacy,Jinan University;Division of Antitumor Pharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences;Institute for Translational Medicine,College of Medicine,Qingdao University;Department of Biochemistry and Biophysics,Institute of Systems Biomedicine,School of Basic Medical Sciences,Peking University Health Science Center;
英文摘要：
Extensive structure-activity relationships(SARs) study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido [4,5-d]pyrimidine privileged scaffold as EGFRC797 S inhibitors.One of the most potent compound 6 i potently suppressed EGFR~(L858 R/T790 M/C797 S) kinase with an IC_(50) value of 3.1 nmol/L,and inhibited the proliferation of BaF3 cells harboring EGFR~(L858 R/T790 M/C797 S) and EGFR~(19 D/T790 M/C797 S) mutants with IC_(50) values of 290 nmol/L and 316 nmol/L,respectively.Further,6 i dose-dependently induced suppression of the phosphorylation of EGFR~(L858 R/T790 M/C797 S) and EGFR~(19 D/T790 M/C797 S) in BaF3 cells.Compound 6 i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer(NSCLC) patients.
英文关键词：
EGFR~(C797S) mutant;;SARs;;2-Oxo-3,4-dihydropyrimido[4,5-d];;pyrimidine;;Clinical resistance;;Fourth-generation inhibitors
中文刊名：
Chinese Chemical Letters
