I-BET762

I-BET762 is a potent inhibitor of the BET family of bromodomains with no activity at bromodomains BAZ2B, SP140, ATAD2, CREBBO, and PCAF [1,2]. IC50’s for H4Ac peptide displacement: BRD2 = 32.5nM, BRD3 = 42.4nM, BRD4 = 36.1nM.1 It was able to suppress proinflammatory proteins by macrophage, block acute inflammation in mice1, and suppressed the inflammatory function of T cells [3]. Inhibition of BET bromodomains results in downregulation of Myc transcription, an important oncogene [4].

References:

1) Nicodeme et al. (2010), Suppression of inflammation by a synthetic histone mimic; Nature 468 1119

2) Mirguet et al. (2013), Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains; J.Med.Chem., 56 7501

3) Bandukwala et al. (2012), Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors; Proc.Natl.Acad.Sci.USA, 109 14532

4) Delmore et al. (2011), BET Bromodomain as a Therapeutic Strategy to Target c-Myc; Cell 146 904