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Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability |
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| Authors: | Liu Qingsong Wang Jinhua Kang Seong A Thoreen Carson C Hur Wooyoung Choi Hwan Geun Waller David L Sim Taebo Sabatini David M Gray Nathanael S |
| Affiliation: | a Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA b Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA c Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA d Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA e Koch Center for Integrative Cancer Research at MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA |
| Abstract: | Starting from small molecule mTOR inhibitor Torin1, replacement of the piperazine ring with a phenyl ring resulted in a new series of mTOR inhibitors (as exemplified by 10) that showed superior potency and selectivity for mTOR, along with significantly improved mouse liver microsome stability and a longer in vivo half-life. |
| Keywords: | mTOR PI3K Torin1 |
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