3s2a

Publication Abstract from PubMed

The phosphoinositide 3-kinase (PI3K) family catalyzes the ATP-dependent phosphorylation of the 3' hydroxyl group of phosphatidylinositols and plays an important role in cell-growth and survival. There is abundant evidence demonstrating that PI3K signaling is dysregulated in many human cancers, suggesting that therapeutics targeting the PI3K pathway may have utility for the treatment of cancer. Our efforts to identify potent, efficacious, and orally available PI3K/mammalian target of rapamycin (mTOR) dual inhibitors resulted in the discovery of a series of substituted quinolines and quinoxalines derivatives. In this report, we describe the structure-activity relationships, selectivity, and pharmacokinetic, data of this series and illustrate the in vivo pharmacodynamic and efficacy data for a representative compound.

Phospshoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Discovery and Structure-Activity Relationships of a Series of Quinoline and Quinoxaline Derivatives.,Nishimura N, Siegmund A, Liu L, Yang K, Bryan MC, Andrews KL, Bo Y, Booker SK, Caenepeel S, Freeman DJ, Liao H, McCarter JD, Mullady EL, San Miguel T, Subramanian R, Tamayo N, Wang L, Whittington DA, Zalameda LP, Zhang N, Hughes PE, Norman MH J Med Chem. 2011 May 25. PMID:21612232^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.