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ID: ALA1137756

Journal: Bioorg Med Chem Lett

Title: Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L).

Authors: Rossi M, Bang JK, Mazur S, Iera JA, Phillips DC, Zambetti GP, Appella DH.

Abstract: 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-x(L) is an important member. This protein binds and inhibits BAK, another protein that promotes apoptosis. While the development of chemical inhibitors that block Bcl-x(L)-BAK association have been the focus of intense research efforts, we demonstrate in this manuscript an alternative strategy to downregulate Bcl-x(L). We have identified a small molecule (Bang52) that induces apoptosis in a lymphoblast-derived cell line by lowering levels of Bcl-x(L). Since Bang52 bears no resemblance to any chemical binder of Bcl-x(L) 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.

CiteXplore: 19349174

DOI: 10.1016/j.bmcl.2009.03.067