Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7-dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors
文献类型：期刊论文
| 作者 | Chen, Haiyang2; Song, Peiran1,3,4; Diao, Yanyan2; Hao, Yongjia2; Dou, Dou2; Wang, Wanqi2; Fang, Xiaoyu2; Wang, Yanling2; Zhao, Zhenjiang2; Ding, Jian1
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| 刊名 | MEDCHEMCOMM
 |
| 出版日期 | 2018-04-01 |
| 卷号 | 9期号:4页码:697-704 |
| ISSN号 | 2040-2503 |
| DOI | 10.1039/c8md00019k |
| 文献子类 | Article |
| 英文摘要 | Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)-mediated signaling pathways responsible for the development and function of B cells, which makes it an attractive target for the treatment of many types of B-cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7-dihydropteridine-based, irreversible BTK inhibitors were reported with IC50 values ranging from 1.9 to 236.6 nM in the enzymatic inhibition assay. Compounds 6 and 7 significantly inhibited the proliferation of Ramos cells which overexpress the BTK enzyme, as well as the autophosphorylation of BTK at Tyr223 and the activation of its downstream signaling molecule PLC gamma 2. Overall, this series of compounds could provide a promising starting point for further development of potent BTK inhibitors for B-cell malignancy treatment. |
| WOS关键词 | CHRONIC LYMPHOCYTIC-LEUKEMIA ; B-CELL MALIGNANCY ; TEC FAMILY ; BTK ; ACTIVATION ; RECEPTOR ; DOMAIN ; EXPRESSION ; IBRUTINIB ; DISEASE |
| 资助项目 | National Key Research and Development Program[2016YFA0502304] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase)[U1501501] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000435859400010 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279815]  |
| 专题 | 药理学第一研究室 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 |
| 通讯作者 | Li, Honglin; Xie, Hua; Xu, Yufang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 2.East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Haiyang,Song, Peiran,Diao, Yanyan,et al. Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7-dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors[J]. MEDCHEMCOMM,2018,9(4):697-704. |
| APA | Chen, Haiyang.,Song, Peiran.,Diao, Yanyan.,Hao, Yongjia.,Dou, Dou.,...&Xu, Yufang.(2018).Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7-dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors.MEDCHEMCOMM,9(4),697-704. |
| MLA | Chen, Haiyang,et al."Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7-dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors".MEDCHEMCOMM 9.4(2018):697-704. |
入库方式： OAI收割
来源：上海药物研究所
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