Definition

An orally available, small molecule inhibitor of AGC group kinases, with potential antineoplastic activity. AT13148 inhibits, in an ATP-competitive manner, the enzymatic activity of two AGC kinases, protein kinase B (PKB or AKT) and p70S6K which play key roles in the PI3K/PKB/mTOR signaling pathway. Blockade of this pathway leads to an inhibition of cell growth and the induction of apoptosis in susceptible tumor cells. PI3K/PKB/mTOR pathway is dysregulated in greater than 50% of tumors, and is often correlated with resistance and increased tumor survival. AGC group kinases are serine/threonine kinases that are regulated by secondary messengers such as cyclic AMP and lipids.