ISAM-CG557 is a selective CB2R agonist with a Ki of 54.6 nM. It reduces intracellular ROS levels and caspase activity, demonstrating significant MAPK bias and moderate G-protein bias, with CB2REC50 values of 0.60 nM for cAMP, 60.9 nM for β-arrestin, and 0.03 nM for MAPK. ISAM-CG557 exerts potent anti-inflammatory effects by decreasing pro-inflammatory cytokines and increasing anti-inflammatory cytokines in cells. It is utilized in the study of neuroinflammation and neurodegenerative diseases.

CB2 receptor:54.6 nM (Ki)

ISAM-CG557 at a concentration of 100 nM for 24 hours significantly reduces pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6) while increasing anti-inflammatory cytokines (IL-10, IL-4) in both unstimulated and LPS-stimulated human THP-1 monocytes and PMA-differentiated macrophages. Moreover, 100 nM ISAM-CG557 is non-toxic to primary neurons isolated from fetal CD1 mouse brains, markedly restoring cell viability reduced by LPS and IFN-γ, and decreasing ROS levels and caspase activity. Furthermore, ISAM-CG557 at concentrations ranging from 0.01 nM to 1 μM over 48 hours prevents neurite shortening caused by MAPT P301L and APP V717I plasmid transfection in a concentration-dependent manner in SH-SY5Y cells differentiated by Retinoic acid and GLP-1.