Medicinal chemistry campaign to synthesize synaptamide analogs (GPR110)

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

During this period, the team has continued to pursue cell-based assays to measure G-protein coupled receptor 110 (GPR110) activation and drive structure-activity-relationship (SAR) of a set of novel synaptamide analogs. SAR studies have identified a potent, selective and metabolically stable GPR110 agonist (dimethyl synaptamide DMS) that has demonstrated promising activity in several models of neuronal damage, such traumatic brain injury and optic nerve damage. The lead molecule DMS has undergone additional evaluation in mouse models of multiple sclerosis with very good results, demonstrating elimination of microglia activation, along elimination of B cell and T cell infiltration. In addition, the efficacy of DMS for the treatment of autism is being evaluated in SETD5 mouse mutant, after observing positive results in normalizing the growth of SETD5 human brain organoids.