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ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets - Nature Medicine

  • ️Elmore, Steven W
  • ️Sun Jan 06 2013

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Acknowledgements

We thank M. Bruncko, E. Fry, L. Hasvold, L. Hexamer, A. Kunzer, A. Petros, X. Song, Z. Tao, L. Wang and X. Wang for contributions to the generation of ABT-199 and related analogs and J. Bouska, and D. Osterling for analytical support. The authors acknowledge G. Chiang and A. Vasudevan for critical reading of this manuscript, L. Belmont, I. Wertz, J. Adams, S. Cory, P. Colman, P. Czabotar and G. Lessene for useful discussions and K. Lowes, E. Litvinovich and L. Roberts for technical analysis. Research performed at the Walter and Eliza Hall Institute (WEHI) was supported by grants and fellowships from the Australian National Health and Medical Research Council (NHMRC, including an Independent Research Institutes Infrastructure Support Scheme (IRIISS) grant), the Australian Cancer Research Foundation, the Leukaemia Foundation of Australia, the Cancer Council of Victoria, the Victorian Cancer Agency, the Victorian State Government Operational Infrastructure Support and the Leukemia Lymphoma Society. The authors acknowledge L.M. Staudt (US National Institutes of Health) for DLBCL cell lines.

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  1. Cheol-Min Park

    Present address: Present address: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.,

Authors and Affiliations

  1. AbbVie Inc., North Chicago, Illinois, USA

    Andrew J Souers, Joel D Leverson, Erwin R Boghaert, Scott L Ackler, Nathaniel D Catron, Jun Chen, Brian D Dayton, Hong Ding, Sari H Enschede, Sha Jin, Peter J Kovar, Lloyd T Lam, Kennan C Marsh, Michael J Mitten, Paul M Nimmer, Anatol Oleksijew, Chang H Park, Cheol-Min Park, Darren C Phillips, Morey L Smith, Gerard M Sullivan, Stephen K Tahir, Chris Tse, Michael D Wendt, Yu Xiao, John C Xue, Haichao Zhang, Rod A Humerickhouse, Saul H Rosenberg & Steven W Elmore

  2. Genentech, Inc., South San Francisco, California, USA

    Wayne J Fairbrother, Sarah G Hymowitz, Jackie Lee, Heather L Maecker & Deepak Sampath

  3. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    David C S Huang, Seong Lin Khaw, Kylie D Mason & Andrew W Roberts

  4. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.,

    David C S Huang, Seong Lin Khaw, Kylie D Mason, Andrew W Roberts & John F Seymour

  5. Department of Clinical Hematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Parkville, Victoria, Australia

    Kylie D Mason & Andrew W Roberts

  6. Department of Hematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    John F Seymour

Authors

  1. Andrew J Souers

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  2. Joel D Leverson

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  3. Erwin R Boghaert

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  4. Scott L Ackler

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  5. Nathaniel D Catron

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  6. Jun Chen

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  7. Brian D Dayton

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  8. Hong Ding

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  9. Sari H Enschede

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  10. Wayne J Fairbrother

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  11. David C S Huang

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  13. Sha Jin

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  14. Seong Lin Khaw

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  16. Lloyd T Lam

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  18. Heather L Maecker

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  19. Kennan C Marsh

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  20. Kylie D Mason

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  21. Michael J Mitten

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  22. Paul M Nimmer

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  23. Anatol Oleksijew

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  24. Chang H Park

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  25. Cheol-Min Park

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  26. Darren C Phillips

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  27. Andrew W Roberts

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  28. Deepak Sampath

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  29. John F Seymour

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  30. Morey L Smith

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  31. Gerard M Sullivan

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  33. Chris Tse

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  34. Michael D Wendt

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  35. Yu Xiao

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  37. Haichao Zhang

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  39. Saul H Rosenberg

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  40. Steven W Elmore

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Contributions

A.J.S., S.W.E., S.H.R., S.G.H., W.J.F., D.C.S.H., J.D.L. and C.T. directed aspects of the preclinical research. A.J.S. and J.D.L. interpreted data and wrote the manuscript. A.W.R., S.H.E., J.F.S. and R.A.H. directed the clinical trial design, generated patient data and interpreted results, and A.W.R. contributed in writing the manuscript. S.L.K. generated in vitro CLL experiments. K.D.M. generated in vitro normal volunteer platelet data. M.J.M., E.R.B., S.L.A., D.S., H.L.M., J.L. and A.O. generated in vivo pharmacology data, and E.R.B. contributed in writing of the manuscript. M.D.W., C.-M.P., G.M.S., H.D. and A.J.S. conceived of or generated the compounds described in the manuscript. C.H.P. generated the X-ray structures. J.D.L., D.C.P., S.J., S.K.T., J.C., J.C.X., P.M.N., Y.X., H.Z., P.J.K., C.T., L.T.L. and M.L.S. performed the biological characterization of ABT-199 and other compounds described in the manuscript. N.D.C., B.D.D. and K.C.M. generated the pharmacokinetic and platelet data in conscious dogs.

Corresponding author

Correspondence to Andrew J Souers.

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Competing interests

A.J.S., J.D.L., E.R.B., S.L.A., N.D.C., J.C., H.D., S.H.E., S.J., P.J.K., L.T.L., K.C.M., M.J.M., P.M.N., A.O., C.H.P., D.C.P., M.L.S., G.M.S., S.K.T., C.T., M.D.W., Y.X., J.C.X., H.Z., R.A.H., S.H.R. and S.W.E. are employees and stockholders of Abbott Laboratories. W.J.F., S.G.H., H.L.M. and D.S. are employees of Genentech, Inc., a member of the Roche group, and are stockholders of Roche Holding, AG. D.C.S.H., S.L.K., K.D.M. and A.W.R. are employees of Walter and Eliza Hall Institute, which receives commercial income and research funding from Genentech, Inc. and Abbott Laboratories.

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Souers, A., Leverson, J., Boghaert, E. et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 19, 202–208 (2013). https://doi.org/10.1038/nm.3048

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  • Received: 17 July 2012

  • Accepted: 29 November 2012

  • Published: 06 January 2013

  • Issue Date: February 2013

  • DOI: https://doi.org/10.1038/nm.3048