FEM-1689 (FEM1689) is a potent, selective σ2R/TMEM97 binding ligand with Ki value of 11 nM.
FEM-1689 is >100-fold more selective for σ2R/TMEM97 than 40 CNS proteins except for σ1R (19-fold) and norepinephrine transporter (NET; 37-fold).
FEM-1689 inhibits the integrated stress response and promotes neurite outgrowth via a σ2R/TMEM97-specific action in primary mouse dorsal root ganglion (DRG) neurons.
FEM-1689 reduces ISR and p-eIF2α levels in human sensory neurons and alleviates the pathogenic engagement of integrated stress response (ISR) by methylglyoxal.
FEM-1689 (10 mg/kg, i.v.) produced analgesic effect in mouse neuropathic pain models.
