BC1261

BC1261 is a first-in-class, selective, orally available small molecule inhibitor of **F-box protein 3 (FBXO3)**. Developed by **Koutif Therapeutics**, it targets the FBXO3-FBXL2 axis to treat inflammatory conditions, specifically **Crohn's disease**. FBXO3 is an E3 ligase subunit that mediates the ubiquitination and degradation of **FBXL2**, a sentinel protein that limits inflammation. By inhibiting FBXO3, BC1261 increases the levels of FBXL2, which in turn promotes the degradation of **TRAF** (tumor necrosis factor receptor associated factors) proteins and the **NLRP3** inflammasome. This mechanism leads to a potent reduction in the release of pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6. BC1261 has demonstrated efficacy in preclinical models of acute and chronic colitis, showing improvements in tissue damage and endoscopic scores comparable to anti-p40 therapies.