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• W4312084443 abstract "The PI3K-Akt-mTOR signaling pathway is a highly frequently activated signal transduction pathway in human malignancies, which has been a hot target for anti-tumoral drug discovery. Based on our previous research, a function-oriented synthesis (FOS) of imidazo[1,2-a]pyrazines and imidazo[1,2-b]pyridazines was conducted, and their anticancer activities in vitro and in vivo were evaluated. Among them, compound 42 exhibited excellent dual PI3K/mTOR inhibitory activity, with IC50 values on PI3Kα and mTOR of 0.06 nM and 3.12 nM, respectively, much better than our previous reported compound 15a. Furthermore, compound 42 exhibited significant in vitro and in vivo anti-tumoral activities, great kinase selectivity, low hepatotoxicity, modest plasma clearance and acceptable oral bioavailability, which is a promising PI3K/mTOR targeted anti-cancer drug candidate." @default.
• W4312084443 created "2023-01-04" @default.
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• W4312084443 date "2023-02-01" @default.
• W4312084443 modified "2023-10-16" @default.
• W4312084443 title "Function-oriented synthesis of Imidazo[1,2-a]pyrazine and Imidazo[1,2-b]pyridazine derivatives as potent PI3K/mTOR dual inhibitors" @default.
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• W4312084443 doi "https://doi.org/10.1016/j.ejmech.2022.115030" @default.
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