An inhibitor of Bcl-2 family proteins induces regression of solid tumours (original) (raw)

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Acknowledgements

We thank T. J. Kipps, L. Rassenti, J. Gribben and L. Vallat for CLL Research Consortium samples, E. Monosov for assistance with confocal imaging, C. Rudin and C. Hann for H345 xenograft studies, and S. Ackler for compound formulation.

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Author notes

1. Tilman Oltersdorf, Steven W. Elmore and Alexander R. Shoemaker: *These authors contributed equally to this work

Authors and Affiliations

1. Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California, 92121, USA
   Tilman Oltersdorf, Robert C. Armstrong, Barbara A. Belli, Thomas L. Deckwerth & Kevin J. Tomaselli
2. Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park, Illinois, 60064, USA
   Steven W. Elmore, Alexander R. Shoemaker, David J. Augeri, Milan Bruncko, Jurgen Dinges, Philip J. Hajduk, Mary K. Joseph, Aaron R. Kunzer, Michael J. Mitten, David G. Nettesheim, ShiChung Ng, Paul M. Nimmer, Jacqueline M. O'Connor, Anatol Oleksijew, Andrew M. Petros, Wang Shen, Stephen K. Tahir, Baole Wang, Michael D. Wendt, Haichao Zhang, Stephen W. Fesik & Saul H. Rosenberg
3. Development, Abbott Laboratories, Abbott Park, Illinois, 60064
   Steven W. Elmore, Alexander R. Shoemaker, David J. Augeri, Milan Bruncko, Jurgen Dinges, Philip J. Hajduk, Mary K. Joseph, Aaron R. Kunzer, Michael J. Mitten, David G. Nettesheim, ShiChung Ng, Paul M. Nimmer, Jacqueline M. O'Connor, Anatol Oleksijew, Andrew M. Petros, Wang Shen, Stephen K. Tahir, Baole Wang, Michael D. Wendt, Haichao Zhang, Stephen W. Fesik & Saul H. Rosenberg
4. The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California, 92037, USA
   Shinichi Kitada & John C. Reed
5. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, 02115, USA
   Stanley J. Korsmeyer
6. Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, 02115, USA
   Stanley J. Korsmeyer & Anthony Letai
7. Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
   Chi Li & Craig B. Thompson

Authors

1. Tilman Oltersdorf
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2. Steven W. Elmore
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3. Alexander R. Shoemaker
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4. Robert C. Armstrong
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5. David J. Augeri
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6. Barbara A. Belli
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7. Milan Bruncko
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8. Thomas L. Deckwerth
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9. Jurgen Dinges
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10. Philip J. Hajduk
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11. Mary K. Joseph
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12. Shinichi Kitada
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13. Stanley J. Korsmeyer
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14. Aaron R. Kunzer
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15. Anthony Letai
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16. Chi Li
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17. Michael J. Mitten
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18. David G. Nettesheim
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19. ShiChung Ng
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20. Paul M. Nimmer
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21. Jacqueline M. O'Connor
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22. Anatol Oleksijew
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23. Andrew M. Petros
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24. John C. Reed
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25. Wang Shen
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26. Stephen K. Tahir
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27. Craig B. Thompson
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28. Kevin J. Tomaselli
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29. Baole Wang
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30. Michael D. Wendt
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31. Haichao Zhang
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32. Stephen W. Fesik
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33. Saul H. Rosenberg
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Corresponding authors

Correspondence toStephen W. Fesik or Saul H. Rosenberg.

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Competing interests

S.W.E., A.R.S., D.J.A., M.B., J.D., P.J.H., M.K.J., A.R.K, M.J.M., D.G.N., S-C.H., P.M.N., J.M.O'C., A.O., A.M.P., W.S., S.K.T., B.W., M.D.W., H.Z., S.W.F. and S.H.R. are current or recent employees of Abbott Laboratories. T.O., K.J.T., R.C.A., B.A.B. and T.L. D. are current or recent employees of Idun Pharmaceuticals.

Supplementary information

Supplementary Figure S1

This figure summarizes the synthetic scheme for the chemical synthesis of ABT-737. (PDF 28 kb)

Supplementary Figure S2

This figure contains NMR-derived structures that illustrate the differences between the binding pockets of Bcl-2 and Bcl-XL. (PPT 2187 kb)

Supplementary Figure S3

This figure illustrates the effects of ABT-737 on cytochrome c release from mitochondria isolated from Bak-/-Bax-/- cells that had been stably transfected with either Bak, Bax, or a control plasmid. (PPT 943 kb)

Supplementary Figure S4

This figure illustrates the enhanced survival effected by ABT-737 in the DoHH-2 systemic model of B-cell Lymphoma. (PPT 35 kb)

Supplementary Tables S1-S5

This file contains NMR and structural statistics for the protein complexes illustrated in Figure 1 and Supplementary Figure 2. (DOC 64 kb)

Supplementary Figure Legends

Legends for Supplementary Figures S1-S4. (DOC 56 kb)

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Oltersdorf, T., Elmore, S., Shoemaker, A. et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours.Nature 435, 677–681 (2005). https://doi.org/10.1038/nature03579

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• Received: 10 December 2004
• Accepted: 31 March 2005
• Published: 15 May 2005
• Issue Date: 02 June 2005
• DOI: https://doi.org/10.1038/nature03579