RB101

RB101 is a synthetic small molecule research compound that acts as a dual enkephalinase inhibitor (DENKI). It is designed as a lipophilic prodrug containing a disulfide bond that allows it to cross the blood-brain barrier. Once inside the central nervous system, the disulfide bond is cleaved to release two selective inhibitors: one targeting aminopeptidase N (APN) and the other targeting neutral endopeptidase (NEP, also known as neprilysin). By simultaneously inhibiting these two zinc-metallopeptidases, RB101 prevents the degradation of endogenous enkephalins (met-enkephalin and leu-enkephalin), thereby increasing their levels and enhancing opioid neurotransmission. In rodent models, RB101 has demonstrated potent antinociceptive, antidepressant, and anxiolytic effects mediated through mu- and delta-opioid receptors. Notably, unlike conventional exogenous opioid agonists, RB101 does not appear to induce respiratory depression, physical dependence, or addictive behaviors. Although it has been a pivotal tool in neuroscience research, RB101 is not orally bioavailable and has not been developed for clinical use in humans, though it served as a lead compound for the development of orally active analogs like RB-120 and RB-3007.

Other names

N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyldithio]-1-oxopropyl)-L-phenylalanine benzyl ester