SMI-6860766

SMI-6860766 is a blocker of CD40-Traf6 interactions and has been reported to ameliorate complications associated with diet-induced obesity in mice. The ability of SMI-6860766 to modulate CD40-Traf6 signaling supports its application in research involving immune-metabolic interactions, inflammatory pathways, obesity-associated biological processes, and CD40-mediated signaling networks.

TRAF1:51 μM (Kd), TRAF2:30 μM (Kd), TRAF3:37 μM (Kd), TRAF6:59 μM

Method: Surface-plasmon-resonance experiments measured direct binding of SMI-6860766 to the C-terminal domains of TRAF1, TRAF2, TRAF3 and TRAF6.
Rresult: SMI-6860766 bound TRAF1, TRAF2, TRAF3 and TRAF6 with Kd values of approximately 51, 30, 37 and 59 μM, respectively.[1]
Method: Primary rat hippocampal neurons were treated with SMI-6860766 during early neuronal development, and dendritic protrusion and spinogenesis-associated endpoints were analyzed.
Rresult: Pharmacological inhibition of TRAF6 reduced dendritic protrusion formation, supporting a role for TRAF6-neuroplastin signaling in early excitatory spinogenesis.[3]

Method: Mice subjected to diet-induced obesity received SMI-6860766, and body weight, glucose tolerance and immune-cell populations in epididymal adipose tissue were assessed.
Rresult: Treatment did not alter weight gain but improved glucose tolerance and reduced CD45-positive leukocytes in epididymal adipose tissue by 69%, including significant reductions in CD4-positive and CD8-positive T cells and macrophages.[2]