Background:

GDC-0068 (RG7440) is a highly selective small molecule inhibitor of Akt with IC50s of 5, 18 and 8 nM for Akt1, Akt2 and Akt3. The PI3K-AKT pathway regulates cell growth, survival and tumorigenesis. GDC-0068 binds to and blocks the activation of AKT, which result in cell cycle arrest, inhibition of tumor cell proliferation and induction of tumor cell death. PI3K-AKT is pathway frequently activated in tumors, thus tumors with PTEN or PI3K mutations, which lead to activation of AKT are with high sensitivity to GDC-0068. GDC-0068 is now used for the treatment of human cancers.

参考文献:

1. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. JF Blake, R Xu, JR Bencsik, D Xiao… - Journal of medicinal  2012

2. Lin J, Sampath D, Nannini MA, et al: Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Canc Res 2013, 19:1760–1772.