QQ客服 官方微博 反馈留言

	Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors
	Wang, Beilei1,2; Deng, Yuanxin1,2; Chen, Yongfei1; Yu, Kailin1,2; Wang, Aoli1,2; Liang, Qianmao1; Wang, Wei1,3; Chen, Cheng1,2; Wu, Hong1,3; Hu, Chen1,2
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2017-09-08
卷号	137页码:545-557
关键词	Btk Kinase Inhibitor Irreversible Inhibitor Structure-activity Relationship B-cell Lymphoma
DOI	10.1016/j.ejmech.2017.06.016
文献子类	Article
英文摘要	Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic analysis of compound 18 revealed an irreversible binding efficacy (k(inact)/K-i) of 0.01 mu M(-1)s(-1). Compound 18 potently inhibited BTK kinase Y223 auto-phosphorylation (EC50 < 100 nM), arrested cell cycle in G0/G1 phase, and induced apoptosis in Ramos, MOLM13 and Pfeiffer cells. We believe these features would make 18 a good pharmacological tool for studying BTK-related pathologies. (C) 2017 Elsevier Masson SAS. All rights reserved.
WOS关键词	X-LINKED AGAMMAGLOBULINEMIA ; DISCOVERY ; GENE ; EXPRESSION ; LYMPHOMA ; LEUKEMIA ; MUTANT ; CELLS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
WOS记录号	WOS:000407412200035
资助机构	National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; National Natural Science Foundation of China(U1432250 ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; Natural Science Foundation of Anhui province(1508085MB23) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; National Key Research and Development Program of China(2016YFA0400900) ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; CAS-SAFEA International Partnership Program for Creative Research Teams ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; Hefei Science Center of CAS(2016HSC-IU007) ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; U1532154 ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207) ; 21402207)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/33629]
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 Field Magnet Lab, Mailbox 1110,350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China 2.Univ Sci & Technol China, Hefei 230036, Anhui, Peoples R China 3.CHMFL HCMTC Target Therapy Joint Lab, 350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China 4.Univ Calif Riverside, Dept Chem, 900 Univ Ave, Riverside, CA 92521 USA 5.Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA 6.Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA 7.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Technol Innovat, Precis Targeted Therapy Discovery Ctr, Hefei 230088, Anhui, Peoples R China 8.Chinese Acad Sci, Hefei Sci Ctr, 350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Wang, Beilei,Deng, Yuanxin,Chen, Yongfei,et al. Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,137:545-557.
APA	Wang, Beilei.,Deng, Yuanxin.,Chen, Yongfei.,Yu, Kailin.,Wang, Aoli.,...&Liu, Jing.(2017).Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,137,545-557.
MLA	Wang, Beilei,et al."Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 137(2017):545-557.

个性服务

查看访问统计

相关权益政策

暂无数据

收藏/分享

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。