A Novel Chemical Series for Inhibiting Bromodomain-containing Protein 4 (BRD4) for Treating Cancer

This technology includes the design, synthesis, and use of a novel chemical series for multiple treatments, including for treating cancer. A series of substituted bicyclic heteroaryl small molecules were found to be a potent inhibitor of bromodomain-containing protein 4 (BRD4) for multiple uses, including cancer. A BRD4 inhibitor is in a class of drugs known as BET inhibitors that are used broadly as anti-inflammatories and as anti-cancer agents. The chemical series exhibited less hepatocyte toxicity compared to existing treatments. For example, the series also identified N-methyl 2-pyridone 1s as a great replacement for dimethylisoxazole, an existing BET inhibitor.