1083326-73-1Relevant articles and documents
Design, synthesis and biological evaluation of novel series of 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold derivatives as PI3Kα inhibitors
Dong, Fu-Dan,Liu, Dan-Dan,Deng, Cheng-Long,Qin, Xiao-chun,Chen, Kai,Wang, Jian,Song, Hong-Rui,Ding, Huai-Wei
, p. 3982 - 3991 (2018)
The abnormal activation of PI3K signaling pathway leads to the occurrence of various cancers. The PI3Kα is frequently mutated and overexpressed in many human cancers. Therefore, the PI3Kα was considered as a promising target in therapeutic treatment of cancer. In this study, two series of compounds containing 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold were synthesized and evaluated antiproliferative activities against three cancer cell lines, including HCT-116, MDA-MB-231 and SNU638. Compound 7f with the most potent antiproliferative activity was selected for further evaluation on normal cells and PI3K kinase. Studies indicated that compound 7f could decrease the phospho-Akt (T308) in a dose-dependent manner. Four key hydrogen bonding interactions were found in the docking of 7f with PI3K enzyme. All the results suggested that 7f was a potent PI3Kα inhibitor.
Novel 4-aminoquinazoline derivatives induce growth inhibition, cell cycle arrest and apoptosis via PI3Kα inhibition
Fan, Yan-Hua,Ding, Huai-Wei,Liu, Dan-Dan,Song, Hong-Rui,Xu, Yong-Nan,Wang, Jian
, p. 1675 - 1685 (2018)
Phosphatidylinositol 3-kinase (PI3K) signaling pathway has diverse functions, including the regulation of cellular survival, proliferation, cell cycle, migration, angiogenesis and apoptosis. Among class I PI3Ks (PI3Kα β γ δ), the PIK3CA gene encoding PI3K
Design, synthesis, and biological evaluation of some novel 4-aminoquinazolines as Pan-PI3K inhibitors
Ding, Huai-Wei,Wang, Shu,Qin, Xiao-Chun,Wang, Jian,Song, Hong-Rui,Zhao, Qing-Chun,Song, Shao-Jiang
, p. 2729 - 2740 (2019)
A series of 4-aminoquinazolines derivatives containing hydrophilic group were designed and identified as potent Pan-PI3K inhibitors in this study. The results of antiproliferative assays in vitro showed that this series of compounds had strong inhibition of tumor growth, especially compound 7b for MCF-7 cells but weak inhibition to normal cells. PI3K kinase assay showed that 7b had high activity for three PI3K isoforms with the IC50 values of picomole. The western blot assay indicated that 7b could decrease the phospho-Akt (S473) in a dose-dependent manner. Further experiments showed that 7b could induce apoptosis in MCF-7 cells. Four key hydrogen bonding interactions were found in the docking of 7b with PI3K kinase. All these results suggested that 7b is a potent PI3K inhibitor and could be considered as a potential candidate for the development of anticancer agents.
PI3K/mTOR protein degradation targeting chimeric compound as well as preparation method and medical application of PI3K/mTOR protein degradation targeting chimeric compound
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, (2021/02/10)
The invention relates to a PI3K/mTOR protein degradation targeting chimeric body (PROTAC) compound as well as a preparation method and medical application thereof. Specifically, the present inventionrelates to a compound represented by a general formula (
PI3 KINASE INHIBITORS AND USES THEREOF
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Paragraph 00191, (2021/10/15)
A compound of the formula (II); a pharmaceutical composition comprising same; and methods for treating a fibrotic disease in a subject.