Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model

doi:10.1038/s41598-017-00482-4

CORC > 合肥物质科学研究院 > 中国科学院合肥物质科学研究院 > 中科院强磁场科学中心

	Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model
	Wu, Hong 1,2; Huang, Qiong 3; Qi, Ziping 1; Chen, Yongfei 1; Wang, Aoli 1,2; Chen, Cheng 1; Liang, Qianmao 1,4; Wang, Jinghua 5; Chen, Wensheng 3; Dong, Jin
刊名	SCIENTIFIC REPORTS
	2017-03-28
卷号	7 期号:无页码:1-10
DOI	10.1038/s41598-017-00482-4
文献子类	Article
英文摘要	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.
WOS关键词	BRUTONS TYROSINE KINASE ; TACI-IG ; PHOSPHORYLATION ; TARGETS ; CELLS ; RATS
WOS研究方向	Science & Technology - Other Topics
语种	英语
WOS记录号	WOS:000397526900001
资助机构	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) ; 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)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/32912]
专题	合肥物质科学研究院_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.