ONC206 is an analogue of ONC201 (Figure 1A), with ~5- to 7-fold higher cytotoxic potency in midline glioma cell lines.4 Preliminary data from a mammalian cell-based assay suggested a D2R antagonist potency for ONC206 of ~320 nM.5 Considering the proposed role for D2R in mediating cytotoxicity, we investigated ONC206 using a real-time functional D2R assay using G-protein-coupled inward rectifier potassium (GIRK) channels. Here, DRD2 is linked to glioma.