C
Christine M. Gardiner
Researcher at GlaxoSmithKline
Publications - 5
Citations - 390
Christine M. Gardiner is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: PI3K/AKT/mTOR pathway & Kinase. The author has an hindex of 3, co-authored 5 publications receiving 343 citations.
Papers
More filters
Journal ArticleDOI
Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin
Steven D. Knight,Nicholas D. Adams,Joelle Lorraine Burgess,Amita M. Chaudhari,Michael G. Darcy,Carla A. Donatelli,Juan I. Luengo,Ken A. Newlander,Cynthia A. Parrish,Lance Ridgers,Martha A. Sarpong,Schmidt Stanley J,Glenn S. Van Aller,Jeffrey D. Carson,Melody Diamond,Patricia A. Elkins,Christine M. Gardiner,Eric Garver,Seth A. Gilbert,Richard R. Gontarek,Jeffrey R. Jackson,Kevin L. Kershner,Lusong Luo,Kaushik Raha,Christian S. Sherk,Chiu-Mei Sung,David Sutton,Peter J. Tummino,Ronald Wegrzyn,Kurt R. Auger,Dashyant Dhanak +30 more
TL;DR: 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.
Journal ArticleDOI
Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors.
Jesus R. Medina,Christopher Becker,Charles W. Blackledge,Celine Duquenne,Yanhong Feng,Seth W. Grant,Dirk A. Heerding,William Hoi Hong Li,William H. Miller,Stuart Paul Romeril,Daryl A. Scherzer,Arthur Shu,Mark A. Bobko,Antony Chadderton,Melissa Dumble,Christine M. Gardiner,Seth A. Gilbert,Qi Liu,Sridhar K. Rabindran,Valery Sudakin,Hong Xiang,Pat Brady,Nino Campobasso,Paris Ward,Jeffrey M. Axten +24 more
TL;DR: The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines, demonstrating the utility of these molecules as tools to further delineate the biology ofPDK1 and the potential pharmacological uses of a PDK 1 inhibitor.
Proceedings ArticleDOI
Abstract C62: Identification of GSK2126458, a highly potent inhibitor of phosphoinositide 3‐kinase (PI3K) and the mammalian target of rapamycin (mTOR)
Steven D. Knight,Nicholas D. Adams,Joelle Lorraine Burgess,Amita M. Chaudhari,Michael G. Darcy,Carla A. Donatelli,Ken A. Newlander,Cynthia A. Parrish,Lance Ridgers,Martha A. Sarpong,Schmidt Stanley J,Glenn S. Van Aller,Jeffrey D. Carson,Patricia A. Elkins,Melody Diamond,Christine M. Gardiner,Eric Garver,Lusong Luo,Kaushik Raha,Chiu-Mei Sung,Peter J. Tummino,Kurt R. Auger,Dashyant Dhanak +22 more
TL;DR: Following a chemistry lead optimization effort, the pyridylsulfonamide GSK2126458 was identified as a highly potent, orally bioavailable, pan‐PI3K and mTOR inhibitor and is being evaluated currently in human clinical trials for the treatment of cancer.
Proceedings ArticleDOI
Abstract C63: Biological characterization of GSK2126458, a novel and potent inhibitor of phosphoinositide 3‐kinase and the mammalian target of rapamycin (mTOR)
Mary Ann Hardwicke,Hong Lu,Lusong Luo,Melody Diamond,Chiu-Mei Sung,Jeffrey D. Carson,Ramona Plant,Christine M. Gardiner,Jamin Wang,Catherine A. Oleykowski,Richard R. Gontarek,Glenn S. Van Aller,Seth A. Gilbert,David Sutton,Peter J. Tummino,Richard Wooster,Steven D. Knight,Jeffrey R. Jackson,Dashyant Dhanak,Kurt R. Auger +19 more
TL;DR: The characterization of the pan‐PI3K pyridylsulfonamide inhibitor GSK2126458 is reported: a very potent, reversible, ATP‐competitive inhibitor of wild‐type PI3K and the ‘hotspot’ activating mutants of p110 found in human cancer.
Proceedings ArticleDOI
Abstract LB-116: GSK2334470: A potent and highly selective inhibitor of PDK1
Jeffrey M. Axten,Jesus R. Medina,Arthur Shu,William Hoi Hong Li,Yanhong Feng,M. Phillip DeYoung,Christine M. Gardiner,Antony Chadderton,Melissa Dumble,Qi Liu,Sridhar K. Rabindran +10 more
TL;DR: The results demonstrate that GSK23334470 is a potent, highly selective PDK1 inhibitor which can decreasePDK1 signaling in a tumor xenograft model and modest antiproliferative activity overall is demonstrated.