VU0810464

VU0810464 (CAS No.: 2126040-21-7) is a potent, selective, non-urea small-molecule activator of G protein-gated inwardly rectifying potassium (GIRK, Kir3) channels, a class of ion channels that modulate neuronal excitability downstream of G protein-coupled receptor signaling. It exhibits nanomolar potency toward neuronal GIRK1/2 and GIRK1/4 channel subtypes and demonstrates preferential activation of neuronal Kir3 channels compared with non-neuronal systems, along with favorable brain penetration properties. In cellular assays, VU0810464 induces concentration-dependent increases in GIRK-mediated currents, supporting its utility as a pharmacological tool for probing GIRK channel function and GPCR-effector coupling in neuronal and heterologous expression systems. In vivo, it has been shown to attenuate stress-induced hyperthermia in mice following systemic administration, consistent with central modulation of neuronal excitability, while displaying limited effects in certain behavioral paradigms. This compound is widely applied in neuroscience and ion channel research for target validation, mechanistic studies of GIRK channel regulation, and early-stage drug discovery efforts focused on neuropsychiatric and neurological disorders, with experimental concentrations or dosing regimens typically tailored to specific assay formats and study objectives.