SMM-189

SMM-189 is a potent and selective small molecule inverse agonist of the cannabinoid receptor-2 (CB2). Developed at the University of Tennessee Health Science Center, it is primarily investigated for its immunomodulatory and anti-inflammatory properties. In preclinical models of inflammatory bowel disease (IBD), SMM-189 has demonstrated the ability to attenuate intestinal inflammation by reducing the infiltration of Th17 cells, neutrophils, and natural killer T (NKT) cells, while promoting the activity of myeloid-derived suppressor cells (MDSCs) and increasing the expression of CB2 and protein kinase A (PKA). Beyond gastrointestinal indications, SMM-189 has also been extensively studied for its potential neuroprotective effects in conditions such as traumatic brain injury (TBI) and stroke, where it appears to modulate microglial activation from a pro-inflammatory M1-like phenotype toward an anti-inflammatory M2-like phenotype.