Study Rationale: The proteins parkin and GCase show a strong genetic link to Parkinson’s disease (PD) and are key players of biological pathways often disrupted in the disorder. This connection makes parkin and Gcase highly attractive targets for PD therapeutics. Yet a paucity of publicly available chemical tools has hampered efforts to develop compounds that interact with these two important players in PD pathology. This lack of access is often due to intellectual property rights. The Bridge Initiative will identify and make available potent and selective compounds against key PD targets to aid in understanding their biology and advancing therapeutic development.
Hypothesis: We propose to develop field-enabling tool compounds against druggable PD targets through medicinal chemistry.
Study Design: With this first iteration of the project, we expect to be able to identify and make publicly available robust and selective small molecules that potentially activate, stabilize or inactivate parkin and GCase, the protein products of the Parkin and GBA1 genes, respectively. We will deploy DNA-encoded library (DEL) technology followed by secondary functional assays to identify and characterize the compounds.
Impact on Diagnosis/Treatment of Parkinson’s disease: We expect to deliver tool compounds that will advance our understanding of the roles played by parkin and Gcase in the biology of PD.
Next Steps for Development: The Bridge Initiative will continue to support projects that aim to accelerate these and other druggable PD targets in future iterations.