Abstract 4477: Characterization of AZD5363, an orally bioavailable, potent ATP-competitive inhibitor of AKT kinases with pharmacodynamic and antitumor activity in preclinical models

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL AKT is a key node in the most frequently de-regulated signaling pathway in human cancer, and has been shown to mediate resistance to a range of cytotoxic, anti-hormonal and targeted therapies. AZD5363 inhibits all AKT isoforms with a potency of 90% inhibition of BT474c xenograft growth. Chronic monotherapy dosing resulted in profound growth inhibition or regression of multiple other xenografts derived from a range of solid tumour types. AZD5363 also greatly enhanced the anti-tumor activity of cytotoxic and novel targeted therapies in xenograft models. It is concluded that AZD5363 is a potent inhibitor of AKT with pharmacodynamic and anti-tumor activity in vivo, and has potential to treat a range of solid and hematological malignancies. AZD5363 is currently in phase 1 clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4477. doi:10.1158/1538-7445.AM2011-4477