Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, invitro and in human tumor xenograft models
文献类型：期刊论文
| 作者 | Long, Fei2,3; He, Ye1,3; Fu, Haoyu3; Li, Yun3; Bao, Xubin3; Wang, Quanren3; Wang, Yigang2; Xie, Chengying1,3 ; Lou, Liguang1,3
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| 刊名 | CANCER SCIENCE
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| 出版日期 | 2019-04-01 |
| 卷号 | 110期号:4页码:1420-1430 |
| ISSN号 | 1347-9032 |
| 关键词 | breast cancer CDK 4/6 drug resistance palbociclib SHR6390 |
| DOI | 10.1111/cas.13957 |
| 通讯作者 | Wang, Yigang(wangyigang43@163.com) ; Xie, Chengying(xiechengying818@simm.ac.cn) ; Lou, Liguang(lglou@mail.shcnc.ac.cn) |
| 英文摘要 | Inhibition of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) pathway is an effective therapeutic strategy against cancer. Here, we performed a preclinical investigation of the antitumor activity of SHR6390, a novel CDK4/6 inhibitor. SHR6390 exhibited potent antiproliferative activity against a wide range of human RB-positive tumor cells in vitro, and exclusively induced G(1) arrest as well as cellular senescence, with a concomitant reduction in the levels of Ser780-phosphorylated RB protein. Compared with the well-known CDK4/6 inhibitor palbociclib, orally administered SHR6390 led to equivalent or improved tumor efficacy against a panel of carcinoma xenografts, and produced marked tumor regression in some models, in association with sustained target inhibition in tumor tissues. Furthermore, SHR6390 overcame resistance to endocrine therapy and HER2-targeting antibody in ER-positive and HER2-positive breast cancer, respectively. Moreover, SHR6390 combined with endocrine therapy exerted remarkable synergistic antitumor activity in ER-positive breast cancer. Taken together, our findings indicate that SHR6390 is a novel CDK4/6 inhibitor with favorable pharmaceutical properties for use as an anticancer agent. |
| WOS关键词 | DEPENDENT KINASE 4/6 ; BREAST-CANCER ; ANTITUMOR-ACTIVITY ; ENDOCRINE THERAPY ; PD 0332991 ; PHASE-II ; PALBOCICLIB ; ABEMACICLIB ; TAMOXIFEN ; EFFICACY |
| 资助项目 | National Natural Science Foundation of China[81273546] ; Science and Technology Commission of Shanghai Municipality[18DZ2293200] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000467640800025 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/289859]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Yigang; Xie, Chengying; Lou, Liguang |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Hangzhou, Zhejiang, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Long, Fei,He, Ye,Fu, Haoyu,et al. Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, invitro and in human tumor xenograft models[J]. CANCER SCIENCE,2019,110(4):1420-1430. |
| APA | Long, Fei.,He, Ye.,Fu, Haoyu.,Li, Yun.,Bao, Xubin.,...&Lou, Liguang.(2019).Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, invitro and in human tumor xenograft models.CANCER SCIENCE,110(4),1420-1430. |
| MLA | Long, Fei,et al."Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, invitro and in human tumor xenograft models".CANCER SCIENCE 110.4(2019):1420-1430. |
入库方式： OAI收割
来源：上海药物研究所
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