南方科技大学知识苑(SUSTech KC): Design, synthesis, and biological evaluation of 3, 5-disubsituted-1H-pyrazolo[3,4-b]pyridines as multiacting inhibitors against microtubule and kinases

题名	Design, synthesis, and biological evaluation of 3, 5-disubsituted-1H-pyrazolo[3,4-b]pyridines as multiacting inhibitors against microtubule and kinases
作者	Ning, Chengqing1,2,3,4,5 ; Tao, Axiao 1,2,3,4 ; Xu, Jing1,2,3,4
通讯作者	Ning, Chengqing; Xu, Jing
发表日期	2023-11-05
DOI	10.1016/j.ejmech.2023.115687
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 影响因子和分区
ISSN	0223-5234
EISSN	1768-3254
卷号	259
摘要	Combination therapy of kinases inhibitors and chemotherapeutics targeting tubulin dynamics is an important strategy to improve therapeutic efficacy and overcome the resistance to single-target drug therapies. Inspired by this, we report herein the rational design of 3,5-disubsituted-1H-pyrazolo[3,4-b]pyridines as multiacting mole-cules that are capable of inhibiting tubulin and kinases simultaneously. Among them, 8g showed excellent antiproliferative activities toward a panel of cancer cell lines. 8g strongly inhibited tubulin assembly and demonstrated a potent inhibition toward FLT3 and Abl1 in both enzymatic and cellular assays. 8g caused a cell cycle arrest at G2/M phase, and significantly disrupted HUVEC tube formation. In vivo efficacy studies showed that 8g significantly inhibited tumor growth on the K562 leukemia xenograft model at 10 mg/kg. Collectively our studies suggest that the excellent antiproliferative potency of 8g may be attributed to its potent inhibitory activity against both microtubule and kinases.
关键词	tubulin ABL1 FLT3 kinase multitarget
相关链接	[来源记录]
收录类别	SCI ; IC
语种	英语
学校署名	第一 ; 通讯
资助项目	Shenzhen Science, Technology and Innovation Commission["JCYJ20220530113004009","JCYJ20220814203252001","ZDSYS20190902093215877"] ; Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis[2020B121201002] ; Guangdong Provincial Key Laboratory of Catalysis[2019BT02Y335] ; Guangdong Innovative Program[2021ZDZX2035] ; Key research projects in colleges and universities in Guangdong Province[C17783101] ; Shenzhen Nobel Prize Scientists Laboratory Project[2020KCXTD016] ; null[JCYJ20190809140611364]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:001053550900001
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
ESI学科分类	CHEMISTRY
来源库	Web of Science
引用统计	被引频次[WOS]：5
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/553393
专题	理学院_化学系前沿与交叉科学研究院深圳格拉布斯研究院
作者单位	1.Southern Univ Sci & Technol, Dept Chem, Shenzhen 518055, Peoples R China 2.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Shenzhen 518055, Peoples R China 3.Southern Univ Sci & Technol, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China 4.Southern Univ Sci & Technol, Shenzhen Key Lab Small Mol Drug Discovery & Synth, Shenzhen 518055, Peoples R China 5.SUSTech Acad Adv Interdisciplinary Studies, Shenzhen 518055, Peoples R China
第一作者单位	化学系; 深圳格拉布斯研究院; 南方科技大学; 前沿与交叉科学研究院
通讯作者单位	化学系; 深圳格拉布斯研究院; 南方科技大学; 前沿与交叉科学研究院
第一作者的第一单位	化学系
推荐引用方式 GB/T 7714	Ning, Chengqing,Tao, Axiao,Xu, Jing. Design, synthesis, and biological evaluation of 3, 5-disubsituted-1H-pyrazolo[3,4-b]pyridines as multiacting inhibitors against microtubule and kinases[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,259.
APA	Ning, Chengqing,Tao, Axiao,&Xu, Jing.(2023).Design, synthesis, and biological evaluation of 3, 5-disubsituted-1H-pyrazolo[3,4-b]pyridines as multiacting inhibitors against microtubule and kinases.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,259.
MLA	Ning, Chengqing,et al."Design, synthesis, and biological evaluation of 3, 5-disubsituted-1H-pyrazolo[3,4-b]pyridines as multiacting inhibitors against microtubule and kinases".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 259(2023).