BH3mimetika
BH3 mimetika, or BH3 mimetics, are a class of small-molecule compounds that imitate the action of BH3-only pro-apoptotic proteins. They bind to the hydrophobic BH3-binding grooves of anti-apoptotic BCL-2 family proteins, such as BCL-2, BCL-XL, BCL-W, MCL-1 and related factors, displacing pro-apoptotic effectors like BIM, BID, PUMA or NOXA. This release promotes mitochondrial outer membrane permeabilization, cytochrome c release, caspase activation and apoptotic cell death. The approach exploits the dependence of many cancers on anti-apoptotic BCL-2 proteins for survival.
Notable agents and development status. Venetoclax (ABT-199) is a selective BCL-2 inhibitor that has achieved clinical
Clinical use and challenges. BH3 mimetics are often tested in combination with chemotherapy, hypomethylating agents, or