1001180-47-7Relevant articles and documents
Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors
Blake, James F.,Xu, Rui,Bencsik, Josef R.,Xiao, Dengming,Kallan, Nicholas C.,Schlachter, Stephen,Mitchell, Ian S.,Spencer, Keith L.,Banka, Anna L.,Wallace, Eli M.,Gloor, Susan L.,Martinson, Matthew,Woessner, Richard D.,Vigers, Guy P.A.,Brandhuber, Barbara J.,Liang, Jun,Safina, Brian S.,Li, Jun,Zhang, Birong,Chabot, Christine,Do, Steven,Lee, Leslie,Oeh, Jason,Sampath, Deepak,Lee, Brian B.,Lin, Kui,Liederer, Bianca M.,Skelton, Nicholas J.
, p. 8110 - 8127 (2012/11/13)
The discovery and optimization of a series of 6,7-dihydro-5H-cyclopenta[d] pyrimidine compounds that are ATP-competitive, selective inhibitors of protein kinase B/Akt is reported. The initial design and optimization was guided by the use of X-ray structures of inhibitors in complex with Akt1 and the closely related protein kinase A. The resulting compounds demonstrate potent inhibition of all three Akt isoforms in biochemical assays and poor inhibition of other members of the cAMP-dependent protein kinase/protein kinase G/protein kinase C extended family and block the phosphorylation of multiple downstream targets of Akt in human cancer cell lines. Biological studies with one such compound, 28 (GDC-0068), demonstrate good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust antitumor response in xenograft models in which the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway is activated. 28 is currently being evaluated in human clinical trials for the treatment of cancer.
COMBINATIONS OF AKT AND MEK INHIBITOR COMPOUNDS, AND METHODS OF USE
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, (2012/10/18)
The invention provides combinations comprising a) compound of formula I : (formula I), or a pharmaceutically acceptable salt thereof; and another agent selected from GDC-0973, PD-0325901, or a pharmaceutically acceptable salt thereof. The combinations are
HYDROXYLATED PYRIMIDYL CYCLOPENTANE AS AKT PROTEIN KINASE INHIBITOR
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Page/Page column 35-36, (2009/09/04)
The present invention provides a compound and pharmaceutically acceptable salts thereof, comprising the Formula I. Also provided are methods of using the compound of this invention as an AKT protein kinase inhibitor and for the treatment of hyperprolifera