This grant builds upon the research from a prior grant: Structural Insights into Activated Intermediates of Parkin Continued
Study Rationale:
Despite broad efforts to develop pharmacological compounds against important PD targets, such as Parkin and GBA, there is a lack of publicly available chemical matter. The availability of potent and selective tool compounds against key PD targets will aid in understanding their biology and advancing the development of therapeutics.
Hypothesis:
The development of field-enabling tool compounds against druggable Parkinson’s disease (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 the protein products of Parkin (parkin) and GBA1 (GCase). DNA-encoded library (DEL) technology followed by secondary functional assays will be performed to identify and characterize the compounds.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Both Parkin and GBA1 show a strong genetic link to PD and are key players of biological pathways often disrupted in PD, making them highly attractive for the PD community. Despite the broad efforts to develop compounds against these two important players in PD biology, there is a lack of publicly available chemical matter, which is often due to intellectual property rights. We expect to deliver tool compounds that will aid in better defining and advancing their underlying biology in relation to the disease.
Next Steps for Development:
The Bridge Initiative will continue to support projects that aim to accelerate these and other Parkinson’s Disease druggable targets in future iterations.