GDC-0068

GDC-0068 (RG7440) is a novel, ATP-competitive and orally bioavailable Akt inhibitor with IC50 values of 5 nM, 18 nM and 8 nM for Akt1, Akt2 and Akt3, respectively. Ipatasertib (GDC-0068) demonstrates potent inhibition of all three Akt isoforms in biochemical assays, but poor inhibition of other AGC family kinases. Moreover, GDC-0068 selectively inhibits cell cycle progression and viability of cancer cell lines driven by PI3K/Akt signaling pathway, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2. GDC-0068 (Ipatasertib) blocks the phosphorylation of multiple downstream targets of Akt in human cancer cell lines. GDC-0068 (RG7440) shows good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust anti-tumor response in xenograft models in which the PI3K-Akt-mTOR pathway is activated.