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.
Design, synthesis, and biological evaluation of novel 3-substituted imidazo[1,2-a]pyridine and quinazolin-4(3H)-one derivatives as PI3Kα inhibitors
Fan, Yan-Hua,Li, Wei,Liu, Dan-Dan,Bai, Meng-Xuan,Song, Hong-Rui,Xu, Yong-Nan,Lee, SangKook,Zhou, Zhi-Peng,Wang, Jian,Ding, Huai-Wei
, p. 95 - 106 (2017)
Phosphatidylinositol 3-kinase (PI3K) is a pivotal regulator of intracellular signaling pathways and considered as a promising target in the development of a therapeutic treatment of cancer. Among the different PI3K subtypes, the PIK3CA gene encoding PI3K
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
Modification of N-(6-(2-methoxy-3-(4-fluorophenylsulfonamido)pyridin-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)acetamide as PI3Ks inhibitor by replacement of the acetamide group with alkylurea
Wang, Xiao-Meng,Mao, Shuai,Cao, Lei,Xie, Xiao-Xiao,Xin, Min-Hang,Lian, Jia-Fang,Cao, Yong-Xiao,Zhang, San-Qi
, p. 5662 - 5671 (2015)
N-(6-(2-Methoxy-3-(4-fluorophenylsulfonamido)pyridin-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)acetamide exhibits remarkable anticancer effects and toxicity when orally administrated. In present study, alkylurea moiety replaced the acetamide group in the c
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.
Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase
Li, Chuchu,Liu, Xiaoqing,Ma, Mingliang,Wang, Haili
, (2022/03/31)
PI3K kinase plays an important role in regulating key processes in cells, such as cell growth, metabolism, proliferation, and apoptosis. The overexpression of PI3K kinase exists in many cancers. The proteolytic target chimera (PROTAC) technology is a new technology that uses the ubiquitin–proteasome system to degrade a given target protein. It has been described that CRBN-based PROTAC targets the degradation of PI3K kinase. However, PROTAC based on VHL has not been reported yet. Here, we connected the previously obtained highly active PI3K inhibitor to the VHL ligand through different small molecules, and obtained a series of PROTAC molecules targeting PI3K kinase. Obtain the most active compound through screening. It provides evidence for the feasibility of PROTAC technology to recruit VHL E3 ligase in PI3K kinase.
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 (
Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation
Chen, Yi,Deng, Mingli,Jia, Yu,Ling, Yun,Liu, Xiaofeng,Lu, Mingzhu,Qiu, Tianze,Xiang, Ruiqing,Yang, Chengbin,Yang, Yongtai,Zhou, Yaming
, (2021/10/19)
Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.
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.
FIBROBLAST ACTIVATION PROTEIN (FAP) TARGETED IMAGING AND THERAPY IN FIBROSIS
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, (2020/05/21)
Excessive deposition of extracellular matrix is a hallmark of Idiopathic pulmonary fibrosis (IPF), it is advantageous to target the cells and the mechanisms associated with this process. By targeting myofibroblasts (specialized contractile fibroblasts) th
