GSK2636771, an effective, specific, orally bioavailable, PI3Kβ inhibitor, has been used in cancer, lymphoma, solid neoplasm, recurrent solid neoplasm, and advanced malignant neoplasm.

PI3Kβ:5.2 nM

In mice, GSK-2636771 (at a dosage of 100 mg/kg) does not elevate glucose/insulin levels. In xenograft tumor models, GSK-2636771 decreases the levels of phosphorylated protein kinase Akt (Ser473).

In PTEN-deficient cell lines, GSK-2636771 exhibits specific inhibitory activity, with EC50 values of 36 nM in human prostate cancer PC-3 and 72 nM in breast cancer HCC70.

Cells are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000 cells/well, optimized for untreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treated with serial dilutions (100pM to 10μM) of GSK2636771. Cell viability is assessed after 72 h of treatment by incubation with CellTiter Blue for 1.5 h. The drug concentration requires for survival of 50% of cells relative to untreated cells (surviving fraction 50, SF50) is determined using GraphPad Prism version 5.0d. Cell lines that fails to achieve the SF50 to a given drug are nominally assigned as the highest concentration screened (i.e. 10μM). At least three independent experiments in triplicate per cell line targeted drug are performed. Association between a mutation and response to a targeted agent is determined using a Fisher’s exact test (GraphPad Prism), and a two-tailed P value <0.05 is considered statistically significant. (Only for Reference)