CLP-280

CLP-280 is a first-in-class small molecule enhancer of the potassium-chloride cotransporter 2 (KCC2), developed by Chlorion Pharma. KCC2 is the primary chloride extruder in mature neurons, and its downregulation or dysfunction leads to increased intracellular chloride concentrations, which impairs the inhibitory effect of GABAergic and glycinergic neurotransmission. By positively modulating KCC2 activity, CLP-280 restores chloride homeostasis and strengthens neuronal inhibition. This mechanism is particularly relevant for treating central nervous system disorders characterized by neuronal hyperexcitability, such as neuropathic pain, epilepsy, and spasticity following spinal cord injury. Unlike traditional GABAergic drugs that act on the receptor, CLP-280 addresses the underlying ionic gradient necessary for proper receptor function.