Figure 7: Schematic depiction of mechanism-guided targeting of the BCL-2 family for cancer therapy.
From: Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy
(a) Differential targeted inhibition of BCL-2, BCL-XL or MCL-1 by ABT-199, ABT-263, anthracyclines, or CDK9 inhibitors. (b) A schematic depicts the interconnected hierarchical model of cell death regulation by the BCL-2 family proteins and differential inhibitory activity of ABT-263 against BCL-2 versus BCL-XL. ABT-263 prevents BCL-2 and BCL-XL from sequestering both activator BH3s and BAX. In contrast, ABT-263 fails to prevent BCL-XL from sequestering BAK. (c) BCL-XL overabundance confers resistance to ABT-263 where BCL-XL prevents the ‘BH3-exposed’ BAK monomers from undergoing homo-oligomerization.
