New mTOR-specific inhibitors came forth from screening and drug discovery efforts. These compounds block activity of both mTOR complexes and are called mTORC1/mTORC2 dual inhibitors. Compounds with this characteristics such as sapanisertib (codenamed INK128), AZD8055, and AZD2014 have entered clinical trials.
A series of these mTOR kinase inhibitors have been studied. Their structure is derived from morpholino pyrazolopyrimidine scaffold.
Improvements of this type of inhibitors have been made by exchanging the morpholines with bridged morpholines in pyrazolopyrimidine inhibitors and results showed increased selectivity to mTOR by 26000 fold.