qHTS to Identify Inhibitors of DYT1 Inclusion Formation

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

During this period, the collaborative team focused on the SAR studies of a lead chemical series that was discovered from qHTS. The team has developed potent analogs with <100 nM activity with amendable ADME properties, but pharmacokinetics and other MDCK reveal potential liability with metabolism and BBB penetrance. These developmental roadblocks are now being addressed with additional rounds of medicinal chemistry optimization. More target engagement probes have also been synthesized, and these probes will be evaluated in target-identification studies. A grant application to the DoD that seeks extend funding for 4 additional years has also been completed with our collaborators at Duke University.