I-CBP112

I-CBP112 is a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor, that inhibits the CBP/p300 bromodomains, enhances acetylation by p300. IC50 & Target: IC50: 5.5±1.1 μM (CBP/p300, Leukemia cell); 9.1±1.2 μM (CBP/p300, Prostate cancer cell)^[1] In Vitro: I-CBP112 significantly enhances acetylation by p300 at the histone H3K18 and H3K23 sites. I-CBP112 stimulated H3K18ac by ~3-fold, I-CBP112 induced enhances acetylation of these same sites by CBP as well as at H4K5. The EC₅₀’s of activation of I-CBP112 on p300- and CBP-mediated H3K18 acetylation are ~2 μM^[1]. Exposure of human and mouse leukemic cell lines to I-CBP112 results in substantially impaired colony formation and induces cellular differentiation without significant cytotoxicity. Exposure of the BioMAP primary cell panel to I-CBP112 results in a unique response on cytokine and marker protein expression^[2]. In Vivo: I-CBP112 significantly reduces the leukemia-initiating potential of mLL-AF9+ AmL cells in a dose-dependent manner 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 opportunities for combinatorial treatment of leukemia and potentially other cancers^[2].