Development of D3 Antagonist for Substance Use Disorder

National Center For Advancing Translational Sciences

Investigators

Abstract

The collaborators at NIDA developed highly selective D3R antagonists that have demonstrated efficacy in multiple preclinical models of addiction, including reduction in self-administration and reinstatement of oxycodone. Importantly, the lead compound under development (R-VK4-116) did not alter the activity of human cardiac potassium channels (hERG) in vitro at pharmacologically relevant concentrations. The team has completed IND-enabling GLP toxicology studies and manufactured cGMP-compliant drug product for use in subsequent clinical trials, with required stability studies ongoing. The IND application was cleared by the FDA to proceed to clinical studies in early 2025. The collaborators at NIDA are preparing for the first-in human clinical trials.