CC214-2

CC214-2 is a small molecule, ATP-competitive dual inhibitor of the mammalian target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2). Developed by Celgene (now part of Bristol Myers Squibb), it was designed to provide more complete suppression of the mTOR pathway compared to first-generation rapalogs, which primarily inhibit mTORC1 and often fail to fully suppress 4E-BP1 phosphorylation or prevent mTORC2-mediated feedback activation of AKT. CC214-2 has shown significant preclinical activity in glioblastoma multiforme (GBM) models, particularly those characterized by EGFRvIII mutations or PTEN deficiency, which drive hyperactivation of the mTOR pathway. The compound is orally bioavailable and has demonstrated the ability to cross the blood-brain barrier, leading to significant tumor growth inhibition in vivo by suppressing protein translation and inducing autophagy.