Inhibitors of BCL2A1/Bfl-1 protein: Potential stock in cancer therapy

The Bcl-2 family members rigorously regulate cell endogenous apoptosis, and targeting anti-apoptotic members is a hot topic in design of anti-cancer drugs. At present, FDA and EMA have approved Bcl-2 inhibitor Venetoclax (ABT-199) for treating chronic lymphocytic leukemia (CLL). However, inhibitors of anti-apoptotic protein BCL2A1/Bfl-1 have not been vigorously developed, and no molecule with ideal activity and selectivity has been found yet. Here we review the biological function and protein structure of Bfl-1, discuss the therapeutic potential and list the currently reported inhibitory peptides and small molecules. This will provide a reference for Bfl-1 targeting drug discovery in the future.