Perturbing pro-survival proteins using quinoxaline derivatives: a structure-activity relationship study.
Basic Information
ID: ALA2010640
Journal: Bioorg Med Chem
Title: Perturbing pro-survival proteins using quinoxaline derivatives: a structure-activity relationship study.
Authors: Rajule R, Bryant VC, Lopez H, Luo X, Natarajan A.
Abstract: In HeLa cells the combinatorial knockdown of Bcl-xL and Mcl-1 is sufficient to induce spontaneous apoptosis. Quinoxaline derivatives were screened for the induction of Mcl-1 dependent apoptosis using a cell line without functional Bcl-xL. Quinoxaline urea analog 1 h was able to specifically induce apoptosis in an Mcl-1 dependent manner. We demonstrate that even small changes to 1h results in dramatic loss of activity. In addition, 1 h and ABT-737 synergistically inhibit cell growth and induce apoptosis. Our results also suggest that 1h could have therapeutic potential against ABT-737 refractory cancer.
CiteXplore: 22386982
DOI: 10.1016/j.bmc.2012.02.022
Patent ID: ┄