Definition

An orally bioavailable protein-protein interaction (PPI) inhibitor that targets the assembly of the NOTCH transcription complex, with potential antineoplastic activity. Upon oral administration, pan-NOTCH PPI inhibitor CB-103 targets and inhibits the NOTCH transcriptional activation complex in the cell nucleus. This inhibits the expression of NOTCH target genes and prevents NOTCH signaling, which may inhibit the proliferation of tumor cells mediated by an overly-active Notch pathway. Overactivation of the Notch signaling pathway, often triggered by activating mutations, has been correlated with increased cellular proliferation and poor prognosis in certain tumor types.