BRD4-IN-12 is a potent and orally active BRD4 inhibitor with an IC50 of 7.9 nM. BRD4-IN-12 downregulates the expression of c-MYC, BCL-2, CDK4 and upregulates p21. BRD4-IN-12 inhibits tumor cell proliferation and promotes apoptosis. BRD4-IN-12 exhibits excellent antitumor effects in the HCT-116 colorectal cancer xenograft model. BRD4-IN-12 can be used for the study of colorectal cancer (CRC) [1].
In Vivo, BRD4-IN-12 (H5) (25 mg/kg or 50 mg/kg; p.o.; once a day; for 18 days) exhibits 52% and 82% tumor growth inhibition (TGI) at 25 mg/kg and 50 mg/kg, respectively, in male BALB/c nude mice bearing HCT-116 colorectal cancer xenografts; maintains stable body weight and causes no significant pathological damage to major organs (heart, liver, spleen, lung, kidney); and downregulates the expression of c-MYC and BCL-2 in tumor tissues; induces increased cell spacing, smaller and rounded nuclei in tumor tissues of male BALB/c nude mice with HCT-116 colorectal cancer xenografts[1].
In Vitro, BRD4-IN-12 (H5) (72 h) shows cytotoxicity against HCT-116 colorectal cancer cells with an IC50 value of 0.84 μM, the cytotoxicity of BRD4-IN-12 induced in HCT-116 cells is BRD4-dependent[1]. BRD4-IN-12 (1.25-5.0 μM; 24 h) downregulates the protein expression of c-MYC, CDK4 and BCL-2, and dose-dependently upregulates the protein expression of p21 in HCT-116 cells[1]. BRD4-IN-12 (20 μM; 3 h) stabilizes BRD4 protein in HCT-116 cell lysates, confirming its intracellular binding to BRD4[1].
References:
[1]. Fang Z, et al. Discovery of an orally bioavailable pyridone-based BRD4 inhibitor with potent antitumor efficacy in colorectal cancer. Eur J Med Chem. 2026 Mar 5;305: 18573.
In Vivo, BRD4-IN-12 (H5) (25 mg/kg or 50 mg/kg; p.o.; once a day; for 18 days) exhibits 52% and 82% tumor growth inhibition (TGI) at 25 mg/kg and 50 mg/kg, respectively, in male BALB/c nude mice bearing HCT-116 colorectal cancer xenografts; maintains stable body weight and causes no significant pathological damage to major organs (heart, liver, spleen, lung, kidney); and downregulates the expression of c-MYC and BCL-2 in tumor tissues; induces increased cell spacing, smaller and rounded nuclei in tumor tissues of male BALB/c nude mice with HCT-116 colorectal cancer xenografts[1].
In Vitro, BRD4-IN-12 (H5) (72 h) shows cytotoxicity against HCT-116 colorectal cancer cells with an IC50 value of 0.84 μM, the cytotoxicity of BRD4-IN-12 induced in HCT-116 cells is BRD4-dependent[1]. BRD4-IN-12 (1.25-5.0 μM; 24 h) downregulates the protein expression of c-MYC, CDK4 and BCL-2, and dose-dependently upregulates the protein expression of p21 in HCT-116 cells[1]. BRD4-IN-12 (20 μM; 3 h) stabilizes BRD4 protein in HCT-116 cell lysates, confirming its intracellular binding to BRD4[1].
References:
[1]. Fang Z, et al. Discovery of an orally bioavailable pyridone-based BRD4 inhibitor with potent antitumor efficacy in colorectal cancer. Eur J Med Chem. 2026 Mar 5;305: 18573.