Mechanism of Action: Protein kinase B (PKB) / serine/threonine protein kinase (AKT) inhibition
Discovery: Derived from a collaborative drug discovery program between AstraZeneca, Astex Pharmaceuticals, The Institute of Cancer Research (ICR) and Cancer Research Technology Limited (CRT). The program began in 2003 through Astex Pharmaceuticals’ collaboration with ICR and CRT. The collaboration with AstraZeneca commenced in July 2005.
How this therapy can help
AZD5363 binds to and inhibits all AKT isoforms. Inhibition of AKT prevents the phosphorylation of AKT substrates that mediate cellular processes, such as cell division, apoptosis, and glucose and fatty acid metabolism. A wide range of solid and hematological malignancies show dysregulated PI3K/AKT/mTOR signaling due to mutations in multiple signaling components. By targeting AKT, the key node in the PIK3/AKT signaling network, this agent may be used as monotherapy or combination therapy for a variety of human cancers.
Inhibition of the PKB/AKT pathway has potential in the treatment of a broad range of tumor types.
AZD5363 is currently being investigated by AstraZeneca in multiple Phase 1 and Phase 2 clinical trials including in combination with paclitaxel in the treatment of triple negative advanced or metastatic breast cancer or in advanced gastric adenocarcinoma; in combination with chemotherapy or with enzalutamide in the treatment of castration resistant prostate cancer; and in combination with the PARP inhibitor, olaparib in the treatment of recurrent endometrial, triple negative breast, ovarian, primary peritoneal and fallopian tube cancers.