Abstract 2945 Linking chromatin modifiers to cell death: gain-of-function small molecules to drug oncogenic transcription

Most drugs to target aberrant epigenetic function are small molecules that inhibit enzymatic activity, degrade the protein, or displace it from a substrate, usually chromatin. This type of mechanism produces a loss-of-function that may result in toxicity if the target is essential in healthy cells. In contrast, we have leveraged chemical induced proximity to activate dominant signaling pathways for a therapeutic effect. I will present our work developing Transcriptional/epigenetic Chemical Inducers of Proximity (TCIPs): small molecules that rewire cancer drivers to activate apoptosis.