Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer
文献类型：期刊论文
| 作者 | Li, Xin4; Yang, Changyong2; Wan, Hong4; Zhang, Ge2; Feng, Jun4; Zhang, Lei4; Chen, Xiaoyan1 ; Zhong, Dafang1; Lou, Liguang1; Tao, Weikang4
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| 刊名 | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
 |
| 出版日期 | 2017-12-15 |
| 卷号 | 110页码:51-61 |
| 关键词 | Pyrotinib HER2-postive breast cancer Irreversible EGFR/HER2 dual tyrosine kinase inhibitor Preclinical Clinical Safety Drug metabolism |
| ISSN号 | 0928-0987 |
| DOI | 10.1016/j.ejps.2017.01.021 |
| 文献子类 | Article; Proceedings Paper |
| 英文摘要 | The discovery and development of a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor SHR1258 (pyrotinib) for the treatment of HER2-postive breast cancer is presented. The structure-activity relationship of lead series and their pharmacokinetic properties were evaluated to identify the potential candidates for further in vivo efficacy studies and preclinical safety assessments. Metabolic pathway and drug-drug interaction were also investigated in preclinical settings. In particular, major metabolites in human and animal species were assessed with regard to potential toxicity or off-target side effects. Overall, the potent and selective EGFR/HER2 dual inhibitor, pyrotinib, displayed robust anti-tumor effects on HER2-overexpressing xenograft models and sufficiently safetywindows in animals aswell as favorable pharmacokinetic properties in human, which substantially ensures current clinical development. Finally, recent advances of pyrotinib in clinical studies are highlighted with very encouraging outcomes in patients with HER2-postive advanced breast cancer. (C) 2017 Elsevier B. V. All rights reserved. |
| WOS关键词 | CYTOCHROME-P450 3A4 ; NERATINIB HKI-272 ; TRASTUZUMAB RESISTANCE ; DRUG DEVELOPMENT ; SOLID TUMORS ; PHASE-I ; RECEPTOR ; AFATINIB ; PHARMACOKINETICS ; METABOLISM |
| 资助项目 | National New Drug Key Program in China[2013ZX09102105] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000414696100007 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272351]  |
| 专题 | 上海药物代谢研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Li, Xin; Wan, Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Jiangsu Hengrui Med Co Ltd, Lianyungang 222047, Jiangsu, Peoples R China; 3.China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Jiangsu, Peoples R China; 4.Shanghai Hengrui Pharmaceut Co Ltd, 279 Wenjing Rd, Shanghai 200245, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Xin,Yang, Changyong,Wan, Hong,et al. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer[J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,2017,110:51-61. |
| APA | Li, Xin.,Yang, Changyong.,Wan, Hong.,Zhang, Ge.,Feng, Jun.,...&Zhang, Lianshan.(2017).Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer.EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,110,51-61. |
| MLA | Li, Xin,et al."Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer".EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 110(2017):51-61. |
入库方式： OAI收割
来源：上海药物研究所
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