Validation of small molecule inhibitors of PARG
Many types of cancer are currently untreatable. In Canada alone, 78,000 cancer-related deaths are seen annually, and obviously, new therapies are needed. We have identified the protein PARG as a potent stimulator of cancer growth and a valid target for anti-cancer therapy. However, specific, cell permeable inhibitors of PARG have historically been difficult to generate. Thus, PARG inhibitors have not yet reached the market nor even clinical trials. Towards this goal we have initiated a project to identify drugs to inhibit PARG. We now propose to test whether these have potent anti-PARG activity in cells and animal models of breast cancer and other cancers. We will also investigate whether an understudied class of chemicals called macrocyclics may also provide inhibitors of PARG. Overall, this work will add great value to our compounds, enabling their subsequent development into novel anti-cancer therapeutics.