Discovery of new BTK inhibitors with B cell suppression activity bearing a 4,6-substituted thieno[3,2-d] pyrimidine scaffold
文献类型：期刊论文
| 作者 | Zhang, Qiumeng2; Zhang, Luyao1,3; Yu, Jie2; Li, Heng1,3; He, Shijun1,3 ; Tang, Wei1,3; Zuo, Jianping1,3; Lu, Wei2
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| 刊名 | RSC ADVANCES
 |
| 出版日期 | 2017 |
| 卷号 | 7期号:42页码:26060-26069 |
| ISSN号 | 2046-2069 |
| DOI | 10.1039/c7ra04261b |
| 文献子类 | Article |
| 英文摘要 | A series of 4,6-substituted thieno[3,2-d] pyrimidine derivatives as Bruton's tyrosine kinase (BTK) inhibitors are designed, synthesized and evaluated for their enzymatic inhibition and immunosuppressive activities. These derivatives exhibit varying inhibitory activities against BTK in vitro. Compound 8 is a novel potent BTK inhibitor which has an IC50 value of 29.9 nM, exerts excellent immunosuppressive activity by inhibiting the proliferation of B cells (IC50 = 284 nM), and shows low cytotoxicity (CC50 = 53 632 nM) on murine splenocytes. In addition, compound 8 displays considerable selectivity between T cells (IC50 > 10 mu M) and B cells. Furthermore, enzymatic assays on more than twenty kinases confirm that compound 8 is more selective than the reference compound Olmutinib. In summary, the results suggest that compound 8 is a potential BTK inhibitor for further evaluation and modification of the C-4 and C-6 position of the thieno[3,2-d] pyrimidine scaffold, which could be considered a new strategy in the development of BTK inhibitors. |
| WOS关键词 | BRUTONS TYROSINE KINASE ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; X-LINKED AGAMMAGLOBULINEMIA ; RHEUMATOID-ARTHRITIS ; BIOLOGICAL EVALUATION ; ANTITUMOR AGENTS ; HDAC INHIBITORS ; PI3 KINASE ; IN-VITRO ; POTENT |
| 资助项目 | "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020337] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000401815800026 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275719]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Zuo, Jianping; Lu, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, Shanghai 201203, Peoples R China; 2.East China Normal Univ, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Qiumeng,Zhang, Luyao,Yu, Jie,et al. Discovery of new BTK inhibitors with B cell suppression activity bearing a 4,6-substituted thieno[3,2-d] pyrimidine scaffold[J]. RSC ADVANCES,2017,7(42):26060-26069. |
| APA | Zhang, Qiumeng.,Zhang, Luyao.,Yu, Jie.,Li, Heng.,He, Shijun.,...&Lu, Wei.(2017).Discovery of new BTK inhibitors with B cell suppression activity bearing a 4,6-substituted thieno[3,2-d] pyrimidine scaffold.RSC ADVANCES,7(42),26060-26069. |
| MLA | Zhang, Qiumeng,et al."Discovery of new BTK inhibitors with B cell suppression activity bearing a 4,6-substituted thieno[3,2-d] pyrimidine scaffold".RSC ADVANCES 7.42(2017):26060-26069. |
入库方式： OAI收割
来源：上海药物研究所
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