I-BET151

The Bromodomain and Extra Terminal domain (BET), a family of four proteins that selectively recognize and bind to acetylated lysine residues in histone, plays a key role in many cellular processes, including inflammatory gene expression, mitosis, and viral/host interaction by controlling the assembly of histone acetylation-dependent chromatin complexes. BET proteins stimulate transcription by recruiting specific types of proteins, for example the super elongation complex (SEC), to chromatin, leading to stimulation of transcriptional elongation of certain target genes including oncogenes and pro-inflammatory cytokines. Targeting BET proteins and displacing them could provide a method of inducing cell cycle arrest and even cell death of defectively programmed cells. I-BET151, a small molecule inhibitor that interacts with BRD4 and BRD3 BET proteins and displaces them from chromatin, has profound efficacy against human and murine MLL-fusion leukemic cell lines, through the induction of early cell cycle arrest and apoptosis. The mode of action is, at least in part, due to suppressing the transcription of key genes (BCL2, C-MYC and CDK6) that are critical for MLL-fusion leukemia maintenance (Ref. 1).

Soluble in DMSO