cathepsin K inhibitors / Oncotelic, Baylor University - LARVOL DELTA

Functionalized small-molecule thiosemicarbazones as inhibitors of cathepsin K-mediated collagenase activity (AACR 2018) - "Recent studies have also confirmed that thiosemicarbazones have the ability to inhibit human and parasitic cathepsin L like-cysteine proteases and the mammalian cathepsin L. This work reports the investigation of a library of thiosemicarbazones synthesized to test their efficiency to inhibit human cathepsin K. Nine thiosemicarbazone (TSC) compounds had IC50 values of less than 50 nM against CatK using a fluorogenic assay with Z-L-Phe-L-Arg-AMC. The activity of CatK was greatly stabilized by the inclusion of chondroitin sulfate in the reaction mixture, but inhibition of the enzyme was not affected. These data indicate that potent, small-molecule TSC CatK inhibitors may be useful to prevent the metastatic spread of cancer to bone."

Breast Cancer • Melanoma • Sarcoma