RO6866945

RO6866945 is a **novel, selective, and brain-penetrant CB2 receptor agonist** developed by Roche. Structurally, it is (3S)-1-[5-tert-butyl-3-[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol (CAS 1433360-72-5) and was synthesized for the targeted activation of cannabinoid receptor 2 (CB2R) with high potency across species (human and mouse CB2 cAMP EC50 0.2 nM, >100% efficacy), while showing negligible activity toward the CB1 receptor[2][3][5]. RO6866945 is orally bioavailable (44% in mice) and penetrates the blood–brain barrier. Pharmacologically, it acts on microglial CB2 receptors within the brain, modulating microglial function and signaling (notably cAMP, CREB, and p38MAPK), and is used primarily as a research tool to probe CB2 receptor function in neuroinflammatory and neurodegenerative contexts, especially Alzheimer's disease models[1][2][3].