Structure-guided rescaffolding of selective antagonists of BCL-XL

Michael F T Koehler, Philippe Bergeron, Edna F Choo, Kevin Lau, Chudi O Ndubaku, Danette Andrea Dudley, Paul Gibbons, Brad Sleebs, Carl S Rye, George Nikolakopoulos, Chinh Thien Bui, Sanjitha Kulasegaram, Wilhelmus J A Kersten, Brian J Smith, Peter Edward Czabotar, Peter M Colman, David CS Huang, Jonathan Bayldon Baell, Keith Geoffrey Watson, Lisa HasvoldZhi-Fu Tao, Le Wang, Andrew J Souers, Steven W Elmore, John A Flygare, Wayne J Fairbrother, Guillaume Lessene

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34 Citations (Scopus)


Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

Original languageEnglish
Pages (from-to)662-667
Number of pages6
JournalACS Medicinal Chemistry Letters
Issue number6
Publication statusPublished - 12 Jun 2014
Externally publishedYes


  • apoptosis
  • BCL-2
  • cancer

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