E3 ubiquitin ligases are often highly specific enzymes that regulate fundamental cellular functions and thus are involved in many human diseases such as inflammation, cancers, and neurodegenerative diseases including Parkinson’s disease. E3 ligases therefore constitute novel therapeutic targets in treating these diseases.
In addition, certain E3 ligases induce the degradation of specific proteins. This activity can be hijacked and directed towards other, disease-causing proteins using bivalent small molecule drugs known as targeted protein degrader drugs.
Together with other researchers at WEHI and in Australia, including medicinal chemists, biologists, and clinicians, we aim to develop small molecule probes and drug candidates that bind E3 ligases. These small molecules may be used as direct E3 ligase inhibitors, or as E3 ligase recruiters in targeted protein degrader drugs.