Strovel, Jeffrey (ConverGene, LLC)
Maloney, David (NCATS)
Yang, Shyh-Ming (NCATS)
Jadhav, Ajit (NCATS)
Urban, Daniel (NCATS)
Yoshioka, Makoto (ConverGene, LLC)
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.
BRD4 has been identified as an important target, particularly for cancer. The chemical series has the potential to be used for a variety of indications including but not limited to cancer, diabetes, inflammation, and acute heart failure, and has a large market potential.
The compounds identified in this chemical series have a novel composition and better drug-like properties.