GDC-0068,AktInhibitor

GDC-0068 is a highly potent, selective, and orally available pan-Akt inhibitor, targeting Akt1, Akt2 and Akt3 with IC₅₀ of 5 nM, 18 nM and 8 nM, respectively. It has >100-fold selectivity over a broad panel of 230 kinases, except PRKG1α and PRKG1β with IC₅₀ of 98 nM and 69 nM. GDC-0068 can effectively block Akt signaling and induce cell cycle arrest in human cancer cell lines in vitro, and exhibit significant efficacy in PTEN- and PI3K mutant xenograft models, including PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. A Phase I study of GDC-0068 in patients with refractory solid tumors is ongoing.

How to Use:

• In vitro:  GDC-0068 was used at 5-10 µM final concentration in vitro and in cellular assays.
• In vivo: GDC-0068 was orally dosed to mice at 50-100 mg/kg once per day, or in combination with MEK inhibitors or chemotherapy agents to significantly reduce the tumor volume. Formulation: 0.5% methylcellulose/0.2% Tween-80.

Reference: 

• 1. Blake JF, et al. Discovery and Preclinical Pharmacology of a Selective ATP-Competitive Akt Inhibitor (GDC-0068) for the Treatment of Human Tumors. (2012) J Med Chem. 55(18):8110-27.
• 2. Heidi M, et al. Abstract 966: Predictive biomarkers of the AKT inhibitor, GDC-0068, in single agent and combination studies. (2012) Cancer Research. Volume 72, Issue 8, Supplement 1
• 3. Kui Lin. Abstract DDT02-01: GDC-0068: A novel, selective, ATP-competitive inhibitor of Akt. (2011) Cancer Research. Volume 71, Issue 8, Supplement 1
• 4. http://www.arraybiopharma.com/_documents/Publication/PubAttachment437.pdf

Products are for research use only. Not for human use.