N1,N2-Bis[[4-(2-pyridinyl)phenyl]methyl]- 1,2-ethanediamine

BC-1215 (N1,N2-Bis[[4-(2-pyridinyl)phenyl]methyl]- 1,2-ethanediamine) is an inhibitor of F-box protein 3 (FBXO3; IC50 = 0.9 μg/mL for Il-1β release). It decreases FBXO3 interaction with F-box/LRR-repeat protein 2 (FBXL2) in a dose-dependent manner and prevents FBXO3-dependent ubiquitination of FBXL2. It also lowers expression of Tnf receptor-associated factors (TRAFs) 1-6 without affecting TRAF1-6 mRNA levels in resting and LPS-stimulated peripheral blood mononuclear cells (PBMCs). BC-1215 (100 μg, i.p., per animal) reduces plasma levels of the inflammatory cytokines Il-6, Tnf, and Il-1β and decreases peritoneal bacteria counts in a mouse model of cecal ligation and puncture-induced sepsis. It also reduces inflammation in mouse models of DSS-induced colitis, paw edema, and ear edema.