Dual Inhibition of PI3K & BET Bromodomain Proteins for Treatment of Haematological Malignancies

Aberrant MYC is implicated in many haematological malignancies and targeting this ‘oncogene of addiction’ remains challenging. Therapeutic strategies targeting single proteins or pathways regulating MYC often demonstrate limited efficacy due to the emergence of resistance. To overcome this a series of chimeric molecules linking PI3K and BET were rationally designed. This thesis examines the chemical, biological and therapeutic effects of a lead dual PI3K/BET inhibitor in a wide range of in vitro and in vivo models of haematological malignancies.