AP-472

AP-472 is a highly selective, small molecule positive allosteric modulator (PAM) of the metabotropic glutamate receptor subtype 4 (mGluR4). It was originally developed at Vanderbilt University’s Warren Center for Neuroscience Drug Discovery and is being advanced by Appello Pharmaceuticals. The drug is designed to enhance mGluR4 signaling in the brain's basal ganglia, aiming to restore balanced neuronal activity disrupted in Parkinson’s disease. Unlike dopamine replacement therapies such as levodopa—which can cause dyskinesias over time—AP-472 targets a non-dopaminergic pathway and is intended to be used adjunctively with levodopa. Preclinical studies demonstrated that systemic administration of AP-472 relieved motor symptoms like rigidity and immobility in models of Parkinson’s disease, with effects augmented when combined with levodopa. Clinical development has included Phase 1 trials evaluating safety, tolerability, and pharmacokinetics in healthy adults[1][3][5][6][7].

Other names

mGlu4-specific PAMs(Appello)