Discovery of Pyridopyrimidinones as Potent and Orally Active Dual Inhibitors of PI3K/mTOR
| Autor: | Amy Guan, Bo Gao, Ning Li, Chengde Wu, Jian Li, Yongguo Li, Yan Pan, Liang Shen, Miao He, Lei Huang, Jikui Sun, Yu Tao, Chichung Chan, Gong Zhen, Hongyu Yuan, Li Yi, Zhengang Peng, Li Jie, Xiulian Lu, Chen Shuhui, Dongling Hao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology Chemistry Organic Chemistry Pharmacology Biochemistry Enzyme assay 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Orally active Pharmacokinetics In vivo 030220 oncology & carcinogenesis Drug Discovery biology.protein Phosphorylation Protein kinase B Tumor xenograft PI3K/AKT/mTOR pathway |
| Zdroj: | ACS Medicinal Chemistry Letters. 9:256-261 |
| ISSN: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.8b00002 |
| Popis: | [Image: see text] The identification and lead optimization of a series of pyridopyrimidinone derivatives are described as a novel class of efficacious dual PI3K/mTOR inhibitors, resulting in the discovery of 31. Compound 31 exhibited high enzyme activity against PI3K and mTOR, potent suppression of Akt and p70s6k phosphorylation in cell assays, and good pharmacokinetic profile. Furthermore, compound 31 demonstrated in vivo efficacy in a PC-3M tumor xenograft model. |
| Databáze: | OpenAIRE |
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