CZ0251

CZ0251 is a preclinical-stage small molecule negative allosteric modulator (NAM) of the fibroblast growth factor 14 (FGF14) and voltage-gated sodium channel Nav1.6 (FGF14/Nav1.6) protein-protein interaction (PPI) complex [P616]. Developed by researchers at the University of Texas Medical Branch (UTMB) and its spinout IonTX, the compound is designed to inhibit the assembly of the FGF14/Nav1.6 complex, thereby suppressing Nav1.6-mediated sodium currents. By modulating this PPI interface, CZ0251 aims to correct aberrant medium spiny neuron (MSN) firing rates in the nucleus accumbens (NAc), which is a key mechanism underlying deficient reward processing and anhedonia [P616]. It is being investigated as a potential first-in-class therapeutic for the treatment of anhedonia in major depressive disorder (MDD) and other psychiatric disorders [P616].