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Koehler MF, Bergeron P, Choo EF, et al. Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL. ACS Med Chem Lett. 2014;5(6):662-7doi: 10.1021/ml500030p.
Koehler, M. F., Bergeron, P., Choo, E. F., Lau, K., Ndubaku, C., Dudley, D., Gibbons, P., Sleebs, B. E., Rye, C. S., Nikolakopoulos, G., Bui, C., Kulasegaram, S., Kersten, W. J., Smith, B. J., Czabotar, P. E., Colman, P. M., Huang, D. C., Baell, J. B., Watson, K. G., Hasvold, L., Tao, Z. F., Wang, L., Souers, A. J., Elmore, S. W., Flygare, J. A., Fairbrother, W. J., & Lessene, G. (2014). Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL. ACS medicinal chemistry letters, 5(6), 662-7. https://doi.org/10.1021/ml500030p
Koehler, Michael F T, et al. "Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL." ACS medicinal chemistry letters vol. 5,6 (2014): 662-7. doi: https://doi.org/10.1021/ml500030p
Koehler MF, Bergeron P, Choo EF, Lau K, Ndubaku C, Dudley D, Gibbons P, Sleebs BE, Rye CS, Nikolakopoulos G, Bui C, Kulasegaram S, Kersten WJ, Smith BJ, Czabotar PE, Colman PM, Huang DC, Baell JB, Watson KG, Hasvold L, Tao ZF, Wang L, Souers AJ, Elmore SW, Flygare JA, Fairbrother WJ, Lessene G. Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL. ACS Med Chem Lett. 2014 Mar 21;5(6):662-7. doi: 10.1021/ml500030p. eCollection 2014 Jun 12. PMID: 24944740; PMCID: PMC4060937.
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ACS Med Chem Lett. 2014 Mar 21;5(6):662-7. doi: 10.1021/ml500030p. eCollection 2014 Jun 12.

Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.

ACS medicinal chemistry letters

Michael F T Koehler, Philippe Bergeron, Edna F Choo, Kevin Lau, Chudi Ndubaku, Danette Dudley, Paul Gibbons, Brad E Sleebs, Carl S Rye, George Nikolakopoulos, Chinh Bui, Sanji Kulasegaram, Wilhelmus J A Kersten, Brian J Smith, Peter E Czabotar, Peter M Colman, David C S Huang, Jonathan B Baell, Keith G Watson, Lisa Hasvold, Zhi-Fu Tao, Le Wang, Andrew J Souers, Steven W Elmore, John A Flygare, Wayne J Fairbrother, Guillaume Lessene

Affiliations

  1. Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
  2. Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
  3. AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.

PMID: 24944740 PMCID: PMC4060937 DOI: 10.1021/ml500030p

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.

Keywords: BCL-2; BCL-XL; apoptosis; cancer

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