BC-1215

**BC-1215** is a small molecule inhibitor of F-box protein 3 (**Fbxo3**), a substrate recognition component of the SCF ubiquitin E3 ligase complex. It disrupts the Fbxo3-Fbxl2 interaction, preventing SCF^Fbxo3-mediated ubiquitination and degradation of Fbxl2, which in turn stabilizes Fbxl2 and promotes ubiquitination/degradation of pro-inflammatory TRAF proteins (TRAF1-6). This suppresses NF-κB signaling and cytokine production (e.g., IL-1β, IL-6, TNFα). BC-1215 demonstrates potent anti-inflammatory effects in preclinical models including LPS-stimulated cells, mouse paw edema, DSS colitis, H1N1 viral pneumonia, septic shock, and ex vivo human lung perfusion, with low nanomolar IC50 for IL-1β release and good predicted oral bioavailability (mouse LD50 ~1.135 g/kg).[1][2][3][5][6]