Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins

…, AR Shoemaker, X Song, SK Tahir, C Tse…

Index: Park, Cheol-Min; Bruncko, Milan; Adickes, Jessica; Bauch, Joy; Ding, Hong; Kunzer, Aaron; Marsh, Kennan C.; Nimmer, Paul; Shoemaker, Alexander R.; Song, Xiaohong; Tahir, Stephen K.; Tse, Christin; Wang, Xilu; Wendt, Michael D.; Yang, Xiufen; Zhang, Haichao; Fesik, Stephen W.; Rosenberg, Saul H.; Elmore, Steven W. Journal of Medicinal Chemistry, 2008 , vol. 51, # 21 p. 6902 - 6915

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Citation Number: 203

Abstract

Overexpression of prosurvival proteins such as Bcl-2 and Bcl-XL has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-XL, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally ...