SGE-301

SGE-301 is a synthetic oxysterol and neuroactive steroid that acts as a potent and selective positive allosteric modulator (PAM) of the N-methyl-D-aspartate receptor (NMDAR). It exhibits preferential activity at GluN2A- and GluN2B-containing NMDAR complexes. Originally developed by Sage Therapeutics (which was acquired by Supernus Pharmaceuticals in July 2025), SGE-301 is optimized for systemic delivery and brain exposure. It enhances NMDAR-mediated synaptic currents by increasing channel open probability and slowing the decay phase of spontaneous excitatory postsynaptic currents. SGE-301 has been extensively investigated in preclinical models of NMDAR hypofunction, including anti-NMDAR encephalitis, where it prevents and reverses antibody-mediated receptor internalization, restores synaptic plasticity (long-term potentiation), and alleviates associated memory and behavioral deficits.

Other names

(3S,8S,9S,10R,13R,14S,17R)-17-((R)-5-hydroxy-5-methylhexan-2-yl)-3,10,13-trimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol