GSK2636771

GSK2636771 is a p110β isoform-specific inhibitor of PIK3 with SF50 more than 1 μM [1].
PI3K (phosphatidylinositol 3-kinase) has 4 catalytic subunits: p110α, β, δ, γ，and δ. PI3K /AKT and related pathways play important roles in cellular growth and survival via internalizing the effects of external growth factors and membrane tyrosine kinases. [2, 3]. Many studies have shown that PI3K is over activated in a variety of cancer cells and inhibition of this pathway have been focused for cancer patients [4].
GSK2636771 is a selective PI3K inhibitor with targeting p110βand has different with the reported GDC-0941 which inhibits all class I PI3K isoforms. In breast cancer cell lines, treatment with GSK2636771 could significantly decrease the phosphorylation of AKT thus inhibits the cell viability. For EEC cell lines with PTEN-mutant, p110β inhibitor GSK2636771 should only combine with p110α selective inhibitor A66 to decrease cell viability [1].
References:
1.Weigelt, B., et al., PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res, 2013. 19(13): p. 3533-44.
2.Costa, C., et al., Measurement of PIP Levels Reveals an Unexpected Role for p110beta in Early Adaptive Responses to p110alpha-Specific Inhibitors in Luminal Breast Cancer. Cancer Cell, 2014. 24(14): p. 00458-9.
3.Schwartz, S., et al., Feedback Suppression of PI3Kalpha Signaling in PTEN-Mutated Tumors Is Relieved by Selective Inhibition of PI3Kbeta. Cancer Cell, 2014. 24(14): p. 00459-0.
4.Slomovitz, B.M. and R.L. Coleman, The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res, 2012. 18(21): p. 5856-64.