tcsc0747 GSK2636771

GSK2636771 is a potent, selective and oral inhibitor of PI3Kβ with a K_i of 0.89 nM and an IC₅₀ of 5.2 nM, showing 900-fold selectivity over p110α and p110γ, and 10-fold selectivity over p110δ isoforms.

In Vitro: GSK2636771 treatment causes cell viability significantly more decreased in the control cells (p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines) than in PTEN-mutant and PTEN wild-type EEC cells. Inhibition of p110β by GSK2636771 or AZD6482 leads to a marked decrease of AKT phosphorylation only in the control prostate and breast cancer cell lines, whereas only marginal effects on AKT activation are observed in EEC cells^[1].

In Vivo: GSK2636771 is a p110β inhibitor, and the p110β primes cells for response to growth factor stimulation. While p110β inhibition suppresses cell and tumor growth, dual targeting of p110α/β enhances apoptosis and provides sustained tumor response in mice model^[2].