BRD4-IN-12

BRD4-IN-12 is a potent and orally active BRD4 inhibitor with an IC50 value of 7.9 nM. It downregulates c-MYC, BCL-2, and CDK4 while upregulating p21. BRD4-IN-12 inhibits the proliferation of tumor cells and promotes apoptosis (apoptosis). It demonstrates excellent antitumor efficacy in HCT-116 colorectal cancer xenograft models and can be used in colorectal cancer (CRC) research.

BRD4:7.90 nM

BRD4-IN-12 (H5) exhibits cytotoxic effects on HCT-116 colorectal cancer cells with an IC50 value of 0.84 μM, indicating that its cytotoxicity is BRD4-dependent. When applied at concentrations of 1.25-5.0 μM for 24 hours, BRD4-IN-12 reduces c-MYC, CDK4, and BCL-2 protein expression and increases p21 expression in a dose-dependent manner in HCT-116 cells. Additionally, a 20 μM concentration of BRD4-IN-12 stabilizes BRD4 protein in HCT-116 cell lysates over 3 hours, confirming its intracellular binding with BRD4.

BRD4-IN-12 (H5) was administered orally at doses of 25 mg/kg and 50 mg/kg once daily for 18 days to male BALB/c nude mice bearing HCT-116 colorectal cancer xenografts, resulting in tumor growth inhibition (TGI) rates of 52% and 82%, respectively. It maintained stable body weight, caused no significant pathological damage to major organs (heart, liver, spleen, lungs, kidneys), downregulated c-MYC and BCL-2 expression in tumor tissues, and induced increased intercellular spaces and smaller, rounder nuclei within the tumor tissue.