HTS led to the identification of a small molecule, PETCM, an Abbot compound, that activates caspase-3 in cell extracts.
In elucidating the mechanism of action of PETCM, the oncoprotein prothymosin-a (Pro-T) and the tumor suppressor putative HLA-DR-associated proteins (PHAP) as important regulators of caspase-3 activation. These proteins appear to mediate distinct steps in the mitochondrial pathway: ProT blocks formation of the apoptosome, an event inhibited by PETCM.  In contrast, PHAP appears to facilitate apoptosome-mediated caspase-9 activation.
The apoptosome is a macromolecular complex that is formed in response to the cellular commitment to apoptodic death.  The apoptosome is crucial to activation of caspase-9.