I-BET726 is an inhibitor of BET family proteins that binds BRD2, BRD3, and BRD4 with high affinity (IC50s = 41, 31, and 22 nM, respectively) and competes with tetra-acetylated histone 4 peptides for binding to the bromodomains of these proteins. It exhibits >1,000-fold selectivity for these proteins over other bromodomain-containing homologs. I-BET726 inhibits cell growth and induces cytotoxicity in neuroblastoma cell lines by modulating the expression of genes involved in apoptosis and Myc signaling. I-BET726 can be administered orally to animals, and it reduces tumor growth in mouse xenograft models of human neuroblastoma.
