文献类型：期刊文章

作　　者：陈加贝[1,2] 郑育奋[1,2] 孔维崎[1,2] 李鑫[1,2] 罗来春[1,2] 韩彦君[1,2] 林松文[1,2] 孙崎[1,2] 葛泽梅[1,2] 李润涛[1,2]

机构地区：[1]北京大学医学部药学院化学生物学系 [2]天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》

基　　金：Ministry of Science and Technology of China(Grant No.2012ZX09103101-042)

年　　份：2017

卷　　号：26

期　　号：10

起止页码：727-736

语　　种：中文

收录情况：CAB、CAS、CSCD、CSCD2017_2018、DOAJ、EMBASE、IC、JST、SCOPUS、ZGKJHX、普通刊

摘　　要：A series of new cyclic phosphoramidate mustard-quinazoline conjugates were designed and synthesized based on the drug candidate EMB-3, a multi-target-directed ligand against tumor cells, and their anti-tumor activities were evaluated on breast cancer and lung cancer cells. Compound 6d exhibited the best anti-tumor performance with IC5o = 0.6 pM （8-fold of EMB-3） on BT474 breast tumor cells. Compound 6d inhibited epidermal growth factor receptor （EGFIL biomarker for NSCLC） and human epidermal growth factor 2 （HER2, biomarker for breast cancer） with IC50 of 18 nM and 78 nM, respectively. The preliminary pharmacokinetic study revealed that 6d was more stable than EMB-3 during the in vivo metabolism. A single dose per os （PO） administration of 6d in rat model （10 mg/kg） resulted in a moderate tl/2 of 1.7 h. These results indicated that compound 6d was a potential lead compound for the treatment of breast cancer.

关 键 词：Phosphoramidate mustard conjugate  ANTI-TUMOR Breast cancer  EGFR/HER2  

分 类 号：R914] R96[药学类]