Cathepsin-IN-5

Cathepsin-IN-5 is a cathepsin inhibitor with IC50 values of 6.2 μM for cathepsin L and 81 nM for cathepsin S. It inhibits the proliferation of cancer cells, induces apoptosis, reduces liver tumor growth in mouse models, and regulates gene expression related to cell death, proliferation, and cellular processes. Cathepsin-IN-5 is applicable for research in hepatocellular carcinoma.

cathepsin S:81 nM

Cathepsin-IN-5 (Compound 1) exhibits time-dependent antiproliferative activity in Hep G2 and Hep 3B liver cancer cell lines, with IC₅₀ values ranging from 1.8 to 6.4 μM at concentrations of 0.15-300 μM over 24-72 hours. Additionally, Cathepsin-IN-5 (7.5-10 μM; 72-96 h) inhibits migration and proliferation in Hep G2 cells during wound healing assays. It also suppresses the activity of endo-cathepsin L (IC₅₀ = 6.2 μM) and cathepsin S (IC₅₀ = 81 nM) in Hep G2 cell lysates in a concentration- and time-dependent manner at 0.1-50 μM for 2-24 hours. Furthermore, Cathepsin-IN-5 (0.1-50 μM; 2.5-24 h) does not induce significant intracellular ROS production in Hep G2 or Hep 3B cells. It leads to concentration- and time-dependent gene expression changes in Hep G2 cells at 5-20 μM for 1-24 hours, enriching pathways related to macroautophagy, apoptosis, and cell migration. The compound (5-20 μM; 6-24 h) also upregulates the expression of sqstm1, gabarapl1, akr1c1, and akap12 in Hep G2 cells and activates apoptosis with increased levels of cleaved PARP1 and cleaved caspase-3.

Cathepsin-IN-5 (Compound 1) administered subcutaneously at 100-150 mg/kg once daily for 15 consecutive days can inhibit the growth of subcutaneous HCC xenografts in nude mice.