A cell-permeable, bioavailable propenone compound that specifically targets TNF receptor-associated factor 6 (TRAF6; Kd = 97 μM for TRAF6 C-domain) and disrupts its functional coupling with CD40. A six-week treatment of C57BL/6 mice fed high fat diet (HFD) with this compound show significant improvement in insulin sensitivity and hepatosteatosis without affecting HFD-induced weight gain. Also reported to reduce gonadal adipose tissue inflammation and diminish the number of CD11b+F4/80+CD11c+ M1 macrophages. Inhibits NF-κB activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (IC50 15.9 μM) and reduce IL-1β and IL-6 expression in anti-CD40 antibody FGK45-stimulated primary bone marrow-derived macrophages.