IKKβ-IN-6

IKKβ-IN-6 is an anti-tumor agent. This compound effectively inhibits IKKβ (IC50: 18.24 μM), thereby reducing the phosphorylation of p65 and IκBα, preventing p65 nuclear translocation, and subsequently regulating NF-κB-controlled genes. Additionally, IKKβ-IN-6 targets topoisomerase I (Topo I), inducing DNA damage, ROS accumulation, mitochondrial membrane potential loss, and S phase arrest. It is applicable in colorectal cancer research.

IKKβ-IN-6 (compound 6i1) exhibits in vitro cytotoxicity against various cancer cell lines at concentrations of 0.84-8.25 μM over 24 hours. At 2.0 μM for 24 hours, IKKβ-IN-6 significantly inhibits topoisomerase I (Topo I) activity in HCT-116 cells, achieving an inhibition rate of 96.37%. It reduces Topo I protein levels in a dose-dependent manner at 0.5-2.0 μM, upregulates γH2AX expression, suppresses the NF-κB pathway, and regulates apoptosis-related proteins. In a dose-dependent fashion at concentrations of 0.5 μM, 1.0 μM, and 2.0 μM over 24 hours, it induces apoptosis in HCT-116 cells, with apoptotic cell percentages of 52.55%, 65.06%, and 79.20%, respectively. Additionally, IKKβ-IN-6 causes S-phase arrest, increases intracellular ROS levels, reduces mitochondrial membrane potential, and inhibits cell migration and invasion in HCT-116 cells, all in a concentration-dependent manner.

IKKβ-IN-6 (2.5-5 mg/kg; intraperitoneal injection; administered once every other day; for 12 days) effectively inhibits the growth of colorectal tumors in BALB/c mice.