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  4. 新药研究国家重点实验室
Identification of methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) as an orally bioavailable, highly potent, PI3K alpha inhibitor for the treatment of advanced solid tumors

文献类型：期刊论文

作者Xiang, Hao-Yue2,3; Wang, Xiang5; Chen, Yan-Hong2; Zhang, Xi5; Tan, Cun2; Wang, Yi5; Su, Yi5; Gao, Zhi-Wei4; Chen, Xiao-Yan4; Xiong, Bing2
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2021
卷号209页码:10
ISSN号0223-5234
关键词PI3K Pyrrolo[2,1-f][1,2,4]triazine Anti-cancer Target therapy
DOI10.1016/j.ejmech.2020.112913
通讯作者Ding, Jian(jding@simm.ac.cn) ; Meng, Ling-Hua(lhmeng@simm.ac.cn) ; Yang, Chun-Hao(chyang@simm.ac.cn)
英文摘要In various human cancers, PI3Ks pathway is ubiquitously dysregulated and thus become a promising anti-cancer target. To discover new potent and selective PI3K inhibitors as potential anticancer drugs, new pyrrolo[2,1-f][1,2,4]triazines were designed, leading to the discovery of compound 37 (CYH33), a selective PI3Ka inhibitor (IC50 = 5.9 nM, beta/alpha, delta/alpha,gamma/alpha= 101-, 13-, 38-fold). Western blot analysis confirmed that compound 37 could inhibit phosphorylation of AKT in human cancer cells to modulate the cellular PI3K/AKT/mTOR pathway. And further evaluation in vivo against SKOV-3 xenograft models demonstrated that a dose-dependent antitumor efficacy was achieved. (C) 2020 Elsevier Masson SAS. All rights reserved.
WOS关键词SMALL-MOLECULE INHIBITORS ; BIOLOGICAL EVALUATION ; DESIGN ; CHALLENGES ; MUTATIONS ; ISOFORM ; DOCKING ; PATHWAY ; KINASE ; GLIDE
资助项目National Natural Science Foundation of China[90713034] ; National Natural Science Foundation of China[81703365] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120185009] ; State Key Laboratory of Drug Research Program[SIMM1705KF-15] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020111] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050407] ; National Science and Technology Major Project Key New Drug Creation and Manufacturing Program[2018ZX09711002-011-014]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号WOS:000600418500053
源URL[http://119.78.100.183/handle/2S10ELR8/296290]  
专题新药研究国家重点实验室
通讯作者Ding, Jian; Meng, Ling-Hua; Yang, Chun-Hao
作者单位1.Shanghai HaiHe Pharmaceut Co Ltd, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Cent South Univ, Coll Chem & Chem Engn, Changsha 410083, Peoples R China
4.Chinese Acad Sci, Ctr Drug Metab Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Xiang, Hao-Yue,Wang, Xiang,Chen, Yan-Hong,et al. Identification of methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) as an orally bioavailable, highly potent, PI3K alpha inhibitor for the treatment of advanced solid tumors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,209:10.
APA Xiang, Hao-Yue.,Wang, Xiang.,Chen, Yan-Hong.,Zhang, Xi.,Tan, Cun.,...&Yang, Chun-Hao.(2021).Identification of methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) as an orally bioavailable, highly potent, PI3K alpha inhibitor for the treatment of advanced solid tumors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,209,10.
MLA Xiang, Hao-Yue,et al."Identification of methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) as an orally bioavailable, highly potent, PI3K alpha inhibitor for the treatment of advanced solid tumors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 209(2021):10.

入库方式： OAI收割

来源：上海药物研究所

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