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 cantarget HsClpP have been developed and optimized againstspecific types of cancers. In general, these compounds disableHsClpP tetradecamer activity by covalently modifying the 14catalytic Ser153 residues located within its lumen (Figure 2A).