2.2.1.2. HsClpP Dysregulation by ADEP Causes Apoptotic Cell Death. In a recent identification and characterization of ADEP analogues showing high specificity for HsClpP, ADEP-28 and ADEP-41 (Figure 3B) were found to activate both the peptidase and protease activities of HsClpP with great potency. In addition, the presence of ADEP at low concentrations was shown to induce dissociation of HsClpX. Biologically, both ADEP-28 and ADEP-41 induced cytotoxicityin HEK293 T-REx cells that express endogenous HsClpP with submicromolar IC50 values (Table 1). Notably, the expression of HsClpP was found to be essential for ADEPinducedcytotoxicity, as illustrated by HEK293 T-REx CLPP−/− cells showing a high tolerance for the drug(Table 1). The severity of the cytotoxicity also increased in proportion to the intracellular level of HsClpP, which implicates greater ADEP sensitivity as the level of HsClpP expression is increased.