Description
AZD-5363 is an oral pan-AKT inhibitor that causes hyperphosphorylation of AKT, locking it in a catalytically inactive state, unable to phosphorylate downstream signaling substrates such as PRAS40 and GSK-β. This compound displays anticancer chemotherapeutic activity, inhibiting proliferation and inducing tumor regression in in vitro and in vivo models of HER2+ breast cancer and prostate cancer. AZD-5363 may also exhibit inhibitory activity against Rho-associated protein kinase (ROCK), p70S6K, PKA, MKK1, MSK1, MSK2, PKC, PKG, PRKX, and RSK2/3.
References
Addie M, Ballard P, Buttar D, et al. Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases. J Med Chem. 2013 Mar 14;56(5):2059-73. PMID: 23394218.
Lamoureux F, Thomas C, Crafter C, et al. Blocked autophagy using lysosomotropic agents sensitizes resistant prostate tumor cells to the novel Akt inhibitor AZD5363. Clin Cancer Res. 2013 Feb 15;19(4):833-44. PMID: 23258740.
Davies BR, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012 Apr;11(4):873-87. PMID: 22294718.
