CUDC-907 is a orally-available, synergistic dual inhibitor of class I PI3K enzymes and class I and II HDAC enzymes. Its inhibition profile against PI3Ka, PI3Kb, and PI3Kd, is 19, 54, and 39 nM, respectively, while HDAC activity is 1.7, 5.0, 1.8, 27, and2.8 nM for HDAC1, HDAC2, HDAC3, HDAC6, and HDAC10, respectively. [1]

Through its dual action activity, CUDC-907 durably inhibits the PI3K-AKT-mTOR pathway and compensatory signaling molecules such as RAF, MEK, MAPK, and STAT3. In H1975 NSCLC cells and BT-474 cells, CUDC-907 was shown to reduce both phosphorylated and total protein levels of MET/EGFR, and HER2/3, respectively. [2] The integration of HDAC inhibition to a PI3K agent is thought to prevent the developmeng of drug resistance. CUDC-907 induces apoptosis and G2-M cell cycle arrest, and also induces caspase-3 and -7 activation in HCT-116 colon cancer cells in a dose-dependent manner.