Screening and kinetic studies of new cathepsin D inhibitors

Abstract

Cathepsin D is a ubiquitous aspartyl lysosomal protease. Because it is associated with the mobility and invasiveness of various cancers, inhibitors of this enzyme have the potential for use as chemotherapeutic drugs. Previously prepared synthetic compounds are being evaluated for their ability to inhibit cathepsin D by determining their IC50 values. The studies were performed using human liver cathepsin D and a fluorogenic substrate (Mca‐Gly‐Lys‐Pro‐Ile‐Leu‐Phe‐Phe‐Arg‐Leu‐Lys(Dnp)‐D‐Arg‐NH2).Several of these compounds were found to be strong inhibitors of cathepsin D. The kinetic properties of four potential inhibitors were characterized. These data will be used in the development of new and more effective inhibitors. Supported by National Cancer Institute at NIH (3R15CA08933‐04 and 3R15CA86933‐04A2S1) and Western Illinois University.