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Discovery of 5-trifluoromethyl-2-aminopyrimidine derivatives as potent dual inhibitors of FLT3 and CHK1

文献类型：期刊论文

作者Deng, Minjie1; Gao, Yue4,5; Wang, Peipei4,5; Du, Wenjing1; Xu, Gaoya4,5; Li, Jia4,5,6,7; Zhou, Yubo5,7; Liu, Tao1,2,3
刊名RSC MEDICINAL CHEMISTRY
出版日期2023-12-07
页码14
DOI10.1039/d3md00597f
通讯作者Zhou, Yubo(ybzhou@simm.ac.cn) ; Liu, Tao(lt601@zju.edu.cn)
英文摘要Here, we discover an FLT3/CHK1 dual inhibitor (30) that exhibits excellent kinase potency and antiproliferative activity against MV4-11 cells. Simultaneously, 30 possesses high selectivity over c-Kit enzyme and low hERG inhibitory ability. Compound 30, meanwhile, overcomes varied resistance in BaF3 cell lines carrying FLT3-TKD and FLT3-ITD mutations. Moreover, 30 demonstrates favorable oral PK properties and kinase selectivity. These conclusions support that compound 30 may be a promising potential FLT3/CHK1 dual agent for further development. Novel FLT3/CHK1 dual agents, the representative compound 30, with favorable oral PK properties, can overcome multiple FLT3-TKD and FLT3-ITD mutations.
WOS关键词ACUTE MYELOID-LEUKEMIA
资助项目National Natural Science Foundation of China[21772174] ; National Natural Science Foundation of China[82273783] ; National Natural Science Foundation of China[82204179] ; National Natural Science Foundation of China[81673466] ; National Natural Science Foundation of China[LZ21H300001] ; Key Project of the Zhejiang Provincial Natural Science Foundation of China
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种英语
出版者ROYAL SOC CHEMISTRY
WOS记录号WOS:001135690400001
源URL[http://119.78.100.183/handle/2S10ELR8/308532]  
专题中国科学院上海药物研究所
通讯作者Zhou, Yubo; Liu, Tao
作者单位1.Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Zijingang Campus, Hangzhou 310058, Peoples R China
2.Zhejiang Univ, Natl Key Lab Adv Drug Delivery & Release Syst, Hangzhou 310058, Peoples R China
3.Zhejiang Univ, Hangzhou Inst Innovat Med, Inst Drug Discovery & Design, Hangzhou 310058, Peoples R China
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
6.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
7.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
推荐引用方式
GB/T 7714		 Deng, Minjie,Gao, Yue,Wang, Peipei,et al. Discovery of 5-trifluoromethyl-2-aminopyrimidine derivatives as potent dual inhibitors of FLT3 and CHK1[J]. RSC MEDICINAL CHEMISTRY,2023:14.
APA Deng, Minjie.,Gao, Yue.,Wang, Peipei.,Du, Wenjing.,Xu, Gaoya.,...&Liu, Tao.(2023).Discovery of 5-trifluoromethyl-2-aminopyrimidine derivatives as potent dual inhibitors of FLT3 and CHK1.RSC MEDICINAL CHEMISTRY,14.
MLA Deng, Minjie,et al."Discovery of 5-trifluoromethyl-2-aminopyrimidine derivatives as potent dual inhibitors of FLT3 and CHK1".RSC MEDICINAL CHEMISTRY (2023):14.

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来源：上海药物研究所

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