Chemical inhibition of the proteolytic activity of HsClpP is perhaps the most direct therapeutic strategy against cancer cells that depend heavily on the protease to proliferate. Several specific inhibitors that can target HsClpP have been developed and optimized against specific types of cancers. In general, these compounds disable HsClpP tetradecamer activity by covalently modifying the 14 catalytic Ser153 residues located within its lumen (Figure 2A).