Small-Molecule Inhibitors of Cathepsin L as Potential Anti-Metastatic Agents




Klope, Matthew Thomas

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The cathepsin family of cysteine proteases is overexpressed in a variety of cancer cell lines. Cathepsin L, one such protease, is secreted into the extracellular space and plays a critical role in degrading the extracellular matrix, and facilitating the metastasis of cancer cells from a primary tumor body to a secondary site. The Pinney and Trawick Research laboratories (Baylor University) have engaged in the design, synthesis, and biological evaluation of a variety of small-molecule inhibitors of cathepsin L for potential use as anti-metastatic agents. Two such compounds, KGP94 and KGP244, have shown significant potency as inhibitors of cathepsin L, and these results along with related biological studies have advanced these compounds as promising anti-metastatic agents. A number of novel small-molecule analogues were synthesized that incorporate the benzophenone and benzoylbenzophenone backbones inherent to these two lead compounds in an ongoing effort to expand the library of compounds that could potentially interact with the cathepsin L active site.



Organic Chemistry