Figure 3.

Representation of the early intrinsic arm of the apoptotic pathway, highlighting the key points identified for therapeutic intervention. Whereas BH3-mimetics (black box) can interfere with the pro-apoptotic BH3-domain interaction with the hydrophobic groove of the anti-apoptotic protein (green box), the novel inhibitor (CS-PEP1, blue box) can interfere with cathepsin S-mediated cleavage of the BAX protein (red box) while also potentially interfering with the respective BH3 domain-hydrophobic groove of BAX with Bcl-xL (green box). Consequently, BAX protein can be stabilized in a manner where it can be readily activated for the induction of MOMP and thus enhance apoptosis (orange boxes).