AZD8055 is a potent and orally bioavailable ATP-competitive inhibitor of mTOR kinase with an IC50 of 0.8 nM. It inhibits both mTORC1 and mTORC2. AZD8055 shows excellent selectivity (1,000-fold) against all class I PI3K isoforms and other members of the PI3K-like kinase family. Furthermore, AZD8055 showed no significant activity against a panel of 260 kinases at concentrations up to 10 µM [1].

The serine/threonine kinase mTOR is crucial for cell growth and proliferation. It regulates cap-dependent translation through the mTORC1 complex and Akt activation through the mTORC2 complex. AZD8055 inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as the phosphorylation of the mTORC2 substrate AKT. AZD8055 potently inhibits proliferation, induces autophagy and apoptosis in different cells. In vivo, AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and phosphorylated AKT and results in significant tumor growth inhibition and/or regression in xenografts representing a broad range of tumor types [1-4].