biostudies-literatureRossi MIntramural NIH HHSNCI NIH HHS2429-34https://www.ebi.ac.uk/biostudies/studies/S-EPMC2808702biostudies-literatureUnknown19(9)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.Bioorganic & medicinal chemistry lettersInduction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L).PMC2808702P30 CA021765CA6320Z01 DK031123-04CA21765Z01 DK031123-03ZIA DK031123-05Zambetti GPMazur SBang JKRossi MAppella DHIera JAPhillips DCfalseInduction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L).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.2009-01-01T00:00:00Z2009 May2020-10-31T09:41:35Z2019-03-27T00:28:03ZS-EPMC28087021934917410.1016/j.bmcl.2009.03.067