VU0463271

VU0463271 is a potent and selective small molecule inhibitor of the potassium-chloride cotransporter 2 (KCC2, encoded by SLC12A5). Developed by researchers at Vanderbilt University, it serves as a critical pharmacological tool for investigating neuronal chloride homeostasis. KCC2 is primarily responsible for maintaining low intracellular chloride concentrations in neurons, which is essential for the inhibitory efficacy of GABA and glycine. By inhibiting KCC2, VU0463271 prevents chloride extrusion, leading to increased intracellular chloride levels and a subsequent reduction in synaptic inhibition. It is widely utilized in preclinical neuroscience research to study the pathophysiology of conditions such as epilepsy, neuropathic pain, and Parkinson's disease, where KCC2 dysfunction is often implicated.