title: Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability.
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.
authors.affiliation: Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Seong A
authors.initials: SA
authors.lastname: Kang
authors.forename: Carson C
authors.initials: CC
authors.lastname: Thoreen
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Hur
authors.forename: Hwan Geun
authors.initials: HG
authors.lastname: Choi
authors.forename: David L
authors.initials: DL
authors.lastname: Waller
authors.forename: Taebo
authors.initials: T
authors.lastname: Sim
authors.forename: David M
authors.initials: DM
authors.lastname: Sabatini
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Gray
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D055808:Drug Discovery; D004355:Drug Stability; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: C553294:1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one; D004791:Enzyme Inhibitors; D009287:Naphthyridines; D058570:TOR Serine-Threonine Kinases