CLP257

CLP257 is a small molecule activator of the potassium-chloride co-transporter 2 (KCC2), a neuron-specific transporter essential for maintaining low intracellular chloride levels. By enhancing KCC2 activity, CLP257 restores chloride homeostasis and GABAergic inhibition, which is often impaired in neurological conditions such as neuropathic pain, epilepsy, and spinal cord injury. It was developed by researchers at the University of Laval and is frequently used as a pharmacological tool in preclinical studies to investigate the therapeutic potential of KCC2 modulation. While CLP257 demonstrated efficacy in animal models, its poor pharmacokinetic profile led to the development of more stable analogs like the carbamate prodrug CLP290.