GDC-0068 is a potent, highly selective, orally available, ATP-competitive pan-AKT inhibitor, targeting Akt1, Akt2 and Akt3 with IC50 of 5 nM, 18 nM and 8 nM, respectively. It demonstrates high selectivity
over more than 200 screened kinases, with >100 fold selectivity for Akt over PKA [1-4].
Akt functions as a central role of the PI3K-Akt-mTOR pathway. It is one of the most frequently activated protein serine/threonine kinases in human malignancies. Inhibiting Akt activity has become an attractive approach for cancer treatment. GDC-0068 blocks the phosphorylation of multiple downstream targets of Akt in human cancer cell lines in a dose-dependent manner. It inhibits cell cycle progression and viability of cancer cell lines, most robustly in cells with activated PI3K-Akt-mTOR pathway driven by PIK3CA , PTEN loss and HER2 amplification. GDC-0068 treatment results in pronounced PD effects in tumor xenograft models including dose dependent suppression of p-PRAS40, P-S6 and P-eIF4G, as well as induction of FOXO nuclear localization. GDC-0086 has exhibited antitumor efficacy in multiple xenograft tumor models. In addition, consistent with the role of Akt in a survival pathway, GDC-0068 also demonstrates enhanced antitumor efficacy when combined with other therapeutic agents. GDC-0068 is currently in Phase 1a and Phase 1b clinical development in cancer patients [1-4].
Technical information:
| Chemical Formula: | C24H32ClN5O2 | |
| CAS #: | 0 | |
| Molecular Weight: | 458 | |
| Purity: | > 98% | |
| Appearance: | White | |
| Chemical Name: | (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | GDC-0068, GDC0068 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
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. J Med Chem. 2012. 55(18):8110-27. Pubmed ID: 22934575 |
| 2. | Lin K. GDC-0068: A novel, selective, ATP-competitive inhibitor of Akt. Cancer Res, 2011, 71(8 Supplement), abstract DDT02-01. |
| 3. | Blake JF. Discovery of GDC-0068: A Selective ATP-competitive Akt Inhibitor for the Treatment of Human Tumors. CHI Next Generation Kinase Inhibitors. June 6-8, 2011. http://www.arraybiopharma.com/_documents/Publication/PubAttachment478.pdf |
| 4. | Abernero J, et al. Targeting the PI3K-Akt-mTOR pathway with GDC-0068, a novel selective ATP competitive Akt inhibitor. http://www.arraybiopharma.com/_documents/Publication/PubAttachment437.pdf |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
