1198171-62-8Relevant articles and documents
Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR
Heffron, Timothy P.,Ndubaku, Chudi O.,Salphati, Laurent,Alicke, Bruno,Cheong, Jonathan,Drobnick, Joy,Edgar, Kyle,Gould, Stephen E.,Lee, Leslie B.,Lesnick, John D.,Lewis, Cristina,Nonomiya, Jim,Pang, Jodie,Plise, Emile G.,Sideris, Steve,Wallin, Jeffrey,Wang, Lan,Zhang, Xiaolin,Olivero, Alan G.
, p. 351 - 356 (2016)
Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). We previously disclosed our successful approach to prospectively design potent and blood-brain barrier (BBB) penetrating PI3K inhibitors. The previously disclosed molecules were ultimately deemed not suitable for clinical development due to projected poor metabolic stability in humans. We, therefore, extended our studies to identify a BBB penetrating inhibitor of PI3K that was also projected to be metabolically stable in human. These efforts required identification of a distinct scaffold for PI3K inhibitors relative to our previous efforts and ultimately resulted in the identification of GDC-0084 (16). The discovery and preclinical characterization of this molecule are described within.
PURINE PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
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, (2009/12/27)
Purine compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
