| Literature DB >> 24900173 |
Steven D Knight1, Nicholas D Adams1, Joelle L Burgess1, Amita M Chaudhari1, Michael G Darcy1, Carla A Donatelli1, Juan I Luengo1, Ken A Newlander1, Cynthia A Parrish1, Lance H Ridgers1, Martha A Sarpong1, Stanley J Schmidt1, Glenn S Van Aller1, Jeffrey D Carson1, Melody A Diamond1, Patricia A Elkins1, Christine M Gardiner1, Eric Garver1, Seth A Gilbert1, Richard R Gontarek1, Jeffrey R Jackson1, Kevin L Kershner1, Lusong Luo1, Kaushik Raha1, Christian S Sherk1, Chiu-Mei Sung1, David Sutton1, Peter J Tummino1, Ronald J Wegrzyn1, Kurt R Auger1, Dashyant Dhanak1.
Abstract
Phosphoinositide 3-kinase α (PI3Kα) is a critical regulator of cell growth and transformation, and its signaling pathway is the most commonly mutated pathway in human cancers. The mammalian target of rapamycin (mTOR), a class IV PI3K protein kinase, is also a central regulator of cell growth, and mTOR inhibitors are believed to augment the antiproliferative efficacy of PI3K/AKT pathway inhibition. 2,4-Difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl}benzenesulfonamide (GSK2126458, 1) has been identified as a highly potent, orally bioavailable inhibitor of PI3Kα and mTOR with in vivo activity in both pharmacodynamic and tumor growth efficacy models. Compound 1 is currently being evaluated in human clinical trials for the treatment of cancer.Entities:
Keywords: GSK2126458; PI3K/AKT pathway; mammalian target of rapamycin; phosphoinositide 3-kinase α
Year: 2010 PMID： 24900173 PMCID： PMC4007793 DOI： 10.1021/ml900028r
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345