Institutional Repository of Chinese Acad Sci, High Field Magnet Lab,Hefei 230031, Anhui, Peoples R China
| Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model | |
Wu, Hong1,2 ; Huang, Qiong3; Qi, Ziping1; Chen, Yongfei1; Wang, Aoli1,2; Chen, Cheng1; Liang, Qianmao1,4; Wang, Jinghua5; Chen, Wensheng3; Dong, Jin; Yu, Kailin1,2; Hu, Chen1,2; Wang, Wenchao1; Liu, Xiaochuan1,4; Deng, Yuanxin1; Wang, Li1,2; Wang, Beilei1,2; Li, Xiaoxiang6; Gray, Nathanael S.5; Liu, Jing1; Wei, Wei3; Liu, Qingsong1,2
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| 2017-03-28 | |
| 发表期刊 | SCIENTIFIC REPORTS
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| 摘要 | BTK plays a critical role in the B cell receptor mediated inflammatory signaling in the rheumatoid arthritis ( RA). Through a rational design approach we discovered a highly selective and potent BTK kinase inhibitor (CHMFL-BTK-11) which exerted its inhibitory efficacy through a covalent bond with BTK Cys481. CHMFL-BTK-11 potently blocked the anti-IgM stimulated BCR signaling in the Ramos cell lines and isolated human primary B cells. It significantly inhibited the LPS stimulated TNF-alpha production in the human PBMC cells but only weakly affecting the normal PBMC cell proliferation. In the adjuvantinduced arthritis rat model, CHMFL-BTK-11 ameliorated the inflammatory response through blockage of proliferation of activated B cells, inhibition of the secretion of the inflammatory factors such as IgG1, IgG2, IgM, IL-6 and PM Phi phagocytosis, stimulation of secretion of IL-10. The high specificity of CHMFL-BTK-11 makes it a useful pharmacological tool to further detect BTK mediated signaling in the pathology of RA. |
| 文章类型 | Article |
| WOS标题词 | Science & Technology |
| DOI | 10.1038/s41598-017-00482-4 |
| 关键词[WOS] | BRUTONS TYROSINE KINASE ; TACI-IG ; PHOSPHORYLATION ; TARGETS ; CELLS ; RATS |
| 收录类别 | SCI |
| 语种 | 英语 |
| 项目资助者 | Youth Foundation of National Natural Science Foundation of China(21402207) ; Youth Foundation of National Natural Science Foundation of China(21402207) ; Youth Foundation of National Natural Science Foundation of China(21402207) ; Youth Foundation of National Natural Science Foundation of China(21402207) ; grant of " Cross- disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; grant of " Cross- disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; grant of " Cross- disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; grant of " Cross- disciplinary Collaborative Teams Program for Science, Technology and Innovation from Chinese Academy of Sciences ; China Thousand Talents Program ; China Thousand Talents Program ; China Thousand Talents Program ; China Thousand Talents Program ; " Hundred Talents Program" of the Chinese Academy of Sciences ; " Hundred Talents Program" of the Chinese Academy of Sciences ; " Hundred Talents Program" of the Chinese Academy of Sciences ; " Hundred Talents Program" of the Chinese Academy of Sciences ; National Program for Support of Top-notch Young Professionals ; National Program for Support of Top-notch Young Professionals ; National Program for Support of Top-notch Young Professionals ; National Program for Support of Top-notch Young Professionals ; Key Science and Technology Program of Anhui province, P.R.China(1501041175) ; Key Science and Technology Program of Anhui province, P.R.China(1501041175) ; Key Science and Technology Program of Anhui province, P.R.China(1501041175) ; Key Science and Technology Program of Anhui province, P.R.China(1501041175) ; Hefei Science Center CAS(2016HSC-IU007) ; Hefei Science Center CAS(2016HSC-IU007) ; Hefei Science Center CAS(2016HSC-IU007) ; Hefei Science Center CAS(2016HSC-IU007) ; State Key Program of National Natural Science of China(81330081) ; State Key Program of National Natural Science of China(81330081) ; State Key Program of National Natural Science of China(81330081) ; State Key Program of National Natural Science of China(81330081) ; National Natural Science Foundation of China(81202596 ; National Natural Science Foundation of China(81202596 ; National Natural Science Foundation of China(81202596 ; National Natural Science Foundation of China(81202596 ; Postdoctoral innovative talent support program(BX201600169) ; Postdoctoral innovative talent support program(BX201600169) ; Postdoctoral innovative talent support program(BX201600169) ; Postdoctoral innovative talent support program(BX201600169) ; Natural Science Foundation of Anhui province(1608085QH180) ; Natural Science Foundation of Anhui province(1608085QH180) ; Natural Science Foundation of Anhui province(1608085QH180) ; Natural Science Foundation of Anhui province(1608085QH180) ; 81603123) ; 81603123) ; 81603123) ; 81603123) |
| WOS研究方向 | Science & Technology - Other Topics |
| WOS类目 | Multidisciplinary Sciences |
| WOS记录号 | WOS:000397526900001 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.hfcas.ac.cn:8080/handle/334002/32912 |
| 专题 | 中科院强磁场科学中心 |
| 作者单位 | 1.Chinese Acad Sci, High Magnet Field Lab, Mailbox 1110,350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China 2.Univ Sci & Technol China, Hefei 230036, Anhui, Peoples R China 3.Anhui Med Univ, Minist Educ, Inst Clin Pharmacol, Anhui Collaborat Innovat Ctr Anti Inflammatory &, Hefei 230032, Peoples R China 4.Univ Sci & Technol China, Dept Chem, Hefei 230036, Anhui, Peoples R China 5.Harvard Med Sch, Dept Biol Chem Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA 6.Anhui New Star Pharmaceutical Inc, Sci Rd 110, Hefei 230000, Anhui, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Hong,Huang, Qiong,Qi, Ziping,et al. Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model[J]. SCIENTIFIC REPORTS,2017,7(无):1-10. |
| APA | Wu, Hong.,Huang, Qiong.,Qi, Ziping.,Chen, Yongfei.,Wang, Aoli.,...&Liu, Qingsong.(2017).Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model.SCIENTIFIC REPORTS,7(无),1-10. |
| MLA | Wu, Hong,et al."Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model".SCIENTIFIC REPORTS 7.无(2017):1-10. |
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| Irreversible inhibit（3966KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | 浏览 下载 | |
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