I-CBP112 is a selective inhibitor of the bromodomain-containing transcription factors. I-CBP112 (1 mM) has little activity against other bromodomains. I-CBP112 targets the CBP/p300 bromodomains. I-CBP112 significantly reduced the leukemia-initiating poten

I-CBP112 markedly increases acetylation by p300 at the histone H3K18 and H3K23 sites. I-CBP112 stimulated H3K18ac by ~3-fold, and induced enhances acetylation of these same sites by CBP as well as at H4K5. The EC50s of activation of I-CBP112 on CBP- and p300-mediated H3K18 acetylation are ~2 μM[1]. In mouse and human leukemia cell lines, I-CBP112 causes substantially impaired colony formation and induces cellular differentiation without significant cytotoxicity. In BioMAP primary cell panel, I-CBP112 results in a unique response on cytokine and marker protein expression[2].

I-CBP112 markedly and dose-dependently reduces the leukemia-initiating potential of mLL-AF9+ AmL cells in vitro and in vivo. The synergistic effects of I-CBP112 and current standard therapy (doxorubicin), as well as emerging treatment strategies (BET inhibition), provide new possibilities for combinatorial treatment of leukemia and potentially other cancers[2].