I-CBP112 is a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor targeting the CBP/p300 bromodomains.

CBP-p300 (Leukemia cells):5.5±1.1 μM (IC50), CBP-p300 (Prostate cancer cells):9.1±1.2 μM (IC50)

将人类和小鼠白血病细胞系暴露于I-CBP112后，显著抑制了菌落形成并且促进了细胞分化，而无明显的细胞毒性。I-CBP112对BioMAP原代细胞板的暴露引起了独特的细胞因子和标志蛋白表达反应。I-CBP112显著增强了p300在组蛋白H3K18和H3K23位点的乙酰化作用。I-CBP112使H3K18ac增加约3倍，I-CBP112诱导的CBP在这些相同位点以及H4K5位点的乙酰化也有所增强。I-CBP112激活p300和CBP介导的H3K18乙酰化的EC50值约为2μM。

I-CBP112 在体外和体内显著以剂量依赖方式降低了MLL-AF9+ AML细胞的白血病发起潜力。

TGase 2 from guinea pig liver is preincubated for 10 min with various concentrations of GK13 or GK921 in 0.1 mL of reaction buffer, with or without 10 mM CaCl2, followed by the addition of 0.4 mL of substrate solution containing 2

I-CBP112 is dissolved in DMSO and diluted with appropriate medium before use. Cells (6000 KG1a and 13000 LNCaP cells/well) are plated in 96-well flat-bottom plates approximately 24 h prior to drug treatment. After 24 h, 10–20% fetal bovine serum-containing medium is replaced with 2.5% serum medium, and cells are treated with I-CBP112 in 0.18% DMSO; 0.18% DMSO is shown to have negligible cell growth effects under the conditions used in our experiments. After being exposed to I-CBP112 for 66 h, cells are subjected to a final concentration of 0.476% [3H]thymidine per well and allowed to proliferate for an additional 6 h (exposure to I-CBP112 for a total of 72 h). Cells are harvested, and the counts of 3H in each well are taken relative to those treated with vehicle alone to quantify the effect of the ligand on proliferation[1].