{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zapevalova MV"],"funding":["Ministry of Science and Higher Education of the Russian Federation","the Ministry of Science and Higher Education of the Russian Federation"],"pagination":["10854"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9503112"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(18)"],"pubmed_abstract":["A (series) range of potential dimorpholinoquinazoline-based inhibitors of the <i>PI3K/Akt/mTOR cascade</i> was synthesized. Several compounds exhibited cytotoxicity towards a panel of cancer cell lines in the low and sub-micromolar range. Compound <b>7c</b> with the highest activity and moderate selectivity towards MCF7 cells which express the mutant type of PI3K was also tested for the ability to inhibit PI3K-(signaling pathway) downstream effectors and associated proteins. Compound <b>7c</b> inhibited the phosphorylation of Akt, mTOR, and S6K at 125-250 nM. It also triggered PARP1 cleavage, ROS production, and cell death via several mechanisms. Inhibition of PI3Kα was observed at a concentration of <b>7b</b> 50 µM and of <b>7c</b> 500 µM and higher, that can indicate minority PI3Kα as a "],"journal":["International journal of molecular sciences"],"pubmed_title":["Synthesis, Molecular Docking, In Vitro and In Vivo Studies of Novel Dimorpholinoquinazoline-Based Potential Inhibitors of PI3K/Akt/mTOR Pathway."],"pmcid":["PMC9503112"],"funding_grant_id":["13.1902.21.0004"],"pubmed_authors":["Maleev AA","Fonareva IP","Svirshchevskaya EV","Kuimov AN","Zapevalova MV","Shchegravina ES","Fedorov AY","Salnikova DI","Ignatov SK","Grishin ID","Konovalova MV","Scherbakov AM","Sorokin DV"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis, Molecular Docking, In Vitro and In Vivo Studies of Novel Dimorpholinoquinazoline-Based Potential Inhibitors of PI3K/Akt/mTOR Pathway.","description":"A (series) range of potential dimorpholinoquinazoline-based inhibitors of the <i>PI3K/Akt/mTOR cascade</i> was synthesized. Several compounds exhibited cytotoxicity towards a panel of cancer cell lines in the low and sub-micromolar range. Compound <b>7c</b> with the highest activity and moderate selectivity towards MCF7 cells which express the mutant type of PI3K was also tested for the ability to inhibit PI3K-(signaling pathway) downstream effectors and associated proteins. Compound <b>7c</b> inhibited the phosphorylation of Akt, mTOR, and S6K at 125-250 nM. It also triggered PARP1 cleavage, ROS production, and cell death via several mechanisms. Inhibition of PI3Kα was observed at a concentration of <b>7b</b> 50 µM and of <b>7c</b> 500 µM and higher, that can indicate minority PI3Kα as a ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-04-08T11:48:57.929Z","creation":"2025-02-19T00:44:29.375Z"},"accession":"S-EPMC9503112","cross_references":{"pubmed":["36142768"],"doi":["10.3390/ijms231810854"]}}