Abstract 1442 Efficacy of BCL-2 Guardian-Inhibiting Drugs

The BCL-2 family proteins regulate apoptosis initiation through mitochondrial poration, which releases apoptosis-inducing proteins such as cytochrome c, which then activate the caspases that execute cell death. However, the overexpression of pro-survival proteins of the BCL-2 family leads to different malignancies. This has made the pro-survival proteins a well-known target for therapeutics. However, the Moldoveanu lab has recently revealed that some of the guardian inhibitors proposed to be potent and selective for MCL-1 are not as potent in inducing apoptosis in cells that contain only the effector BAK + MCL-1 and none of the other BCL-2 family proteins, which may explain why the inhibitors failed in clinical trials due to toxicity.