YZG-331

YZG-331 is an investigational, orally active small-molecule adenosine analog originally developed by the Institute of Materia Medica of the Chinese Academy of Medical Sciences. Derived from structural modification of N6-(4-hydroxybenzyl)adenine riboside (NHBA)—a compound found in the traditional Chinese medicinal herb *Gastrodia elata*—YZG-331 is being investigated for the treatment of insomnia and sleep disorders, as well as postoperative cognitive dysfunction (POCD). It acts primarily as an agonist of the adenosine A1 and A2A receptors, and has also been shown to modulate GABAergic signaling by agonizing glutamate decarboxylase (GAD) to increase GABA levels, and to act as an agonist of solute carrier family 22 member 3 (OCT3) and solute carrier family 7 member 5 (LAT1). Additionally, YZG-331 acts as an allosteric potentiator of magnesium-dependent NMDA receptor blockade, protecting against excitotoxicity. In insomnia models, its sleep-promoting effects are also mediated via the gut-brain axis, where gut microbiota (specifically *Lactobacillus reuteri*) metabolize YZG-331 to its active metabolite M2, promoting tryptophan-to-serotonin (5-HT) conversion.

Other names

N6-[(S)-1-(phenyl)-propyl]-adenine ribosideN6-[(S)-1-(phenyl)propyl]adenosine