CLP-290

CLP-290 is a small molecule prodrug of CLP-257, designed to enhance the function of the neuronal K+/Cl- cotransporter 2 (KCC2). KCC2 is essential for maintaining low intracellular chloride levels in neurons, which is critical for the inhibitory efficacy of GABAergic and glycinergic signaling. In conditions such as mesial temporal lobe epilepsy (mTLE), neuropathic pain, and spinal cord injury, KCC2 expression or function is often reduced, leading to depolarizing GABA signaling and neuronal hyperexcitability. CLP-290 acts by increasing KCC2 surface expression and clustering, thereby restoring chloride homeostasis and suppressing spontaneous epileptiform activity. It was specifically developed to improve the pharmacokinetic profile and oral bioavailability of its parent compound, CLP-257, and has shown significant therapeutic potential in preclinical models of drug-resistant epilepsy.