Structure-guided rescaffolding of selective antagonists of BCL-XL Academic Article uri icon

abstract

  • 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.

authors

  • Koehler, MFT
  • Bergeron, P
  • Choo, EF
  • Lau, K
  • Ndubaku, C
  • Dudley, D
  • Gibbons, P
  • Sleebs, BE
  • Rye, CS
  • Nikolakopoulos, G
  • Bui, C
  • Kulasegaram, S
  • Kersten, WJA
  • Smith, BJ
  • Czabotar, PE
  • Colman, PM
  • Huang, DCS
  • Baell, JB
  • Watson, KG
  • Hasvold, L
  • Tao, Z-F
  • Wang, L
  • Souers, AJ
  • Elmore, SW
  • Flygare, JA
  • Fairbrother, WJ
  • Lessene, G

publication date

  • 2014