CC214-1

CC214-1 is an orally bioavailable, ATP-competitive small molecule inhibitor of the mechanistic target of rapamycin (mTOR) kinase, originally developed by Celgene (now Bristol Myers Squibb). Unlike first-generation mTOR inhibitors (rapalogs) such as rapamycin, which primarily target the mTORC1 complex, CC214-1 provides dual inhibition of both mTORC1 and mTORC2. This dual mechanism allows for more potent suppression of downstream effectors, including 4E-BP1 phosphorylation and protein translation, which are often incompletely inhibited by rapalogs. Preclinical studies in glioblastoma (GBM) models have demonstrated that CC214-1 is particularly effective against tumors driven by EGFRvIII mutations or PTEN loss, both of which hyperactivate the mTOR pathway. Additionally, CC214-1 has been shown to induce autophagy; when combined with autophagy inhibitors like chloroquine, it can significantly enhance apoptotic cell death in cancer cells.