Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-xL

Cancer cells evade death by over-producing specific proteins that inhibit apoptosis. One such group of proteins is the Bcl-2 family, of which Bcl-xL is an important member. This protein binds and inhibits BAK, another protein that promotes apoptosis. While the development of chemical inhibitors that block Bcl-xL-BAK association have been the focus of intense research efforts, we demonstrate in this manuscript an alternative strategy to downregulate Bcl-xL. We have identified a small molecule (Bang52) that induces apoptosis in a lymphoblast-derived cell line by lowering levels of Bcl-xL. Since Bang52 bears no resemblance to any chemical binder of Bcl-xL we believe that degradation of the protein is stimulated by a new type of pathway. These findings highlight a novel approach to the development of small molecules that promote apoptosis.