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An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Author

Listed:
  • Tilman Oltersdorf

    (Idun Pharmaceuticals)

  • Steven W. Elmore

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Alexander R. Shoemaker

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Robert C. Armstrong

    (Idun Pharmaceuticals)

  • David J. Augeri

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Barbara A. Belli

    (Idun Pharmaceuticals)

  • Milan Bruncko

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Thomas L. Deckwerth

    (Idun Pharmaceuticals)

  • Jurgen Dinges

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Philip J. Hajduk

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Mary K. Joseph

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Shinichi Kitada

    (The Burnham Institute)

  • Stanley J. Korsmeyer

    (Harvard Medical School
    Dana-Farber Cancer Institute)

  • Aaron R. Kunzer

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Anthony Letai

    (Dana-Farber Cancer Institute)

  • Chi Li

    (University of Pennsylvania)

  • Michael J. Mitten

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • David G. Nettesheim

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • ShiChung Ng

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Paul M. Nimmer

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Jacqueline M. O'Connor

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Anatol Oleksijew

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Andrew M. Petros

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • John C. Reed

    (The Burnham Institute)

  • Wang Shen

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Stephen K. Tahir

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Craig B. Thompson

    (University of Pennsylvania)

  • Kevin J. Tomaselli

    (Idun Pharmaceuticals)

  • Baole Wang

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Michael D. Wendt

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Haichao Zhang

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Stephen W. Fesik

    (Abbott Laboratories
    Development, Abbott Laboratories)

  • Saul H. Rosenberg

    (Abbott Laboratories
    Development, Abbott Laboratories)

Abstract

Novel antitumour drug Bcl-2 proteins are important regulators of programmed cell death (apoptosis) and are overexpressed in many cancers, contributing to tumour growth and resistance to treatment. Some of the latest techniques in drug design, including NMR-based screening, parallel synthesis, and structure-based design, have been used to develop a new small-molecule Bcl-2 inhibitor called ABT-737. It is three orders of magnitude more potent than any previous Bcl-2 inhibitor, and it looks as if this compound could be useful therapeutically. On its own, ABT-737 kills some cancer cell lines, including cells from lymphoma and small-cell lung carcinomas; in addition, it enhances the effects of chemotherapeutics and radiation on other cancer cell lines.

Suggested Citation

  • Tilman Oltersdorf & Steven W. Elmore & Alexander R. Shoemaker & Robert C. Armstrong & David J. Augeri & Barbara A. Belli & Milan Bruncko & Thomas L. Deckwerth & Jurgen Dinges & Philip J. Hajduk & Mary, 2005. "An inhibitor of Bcl-2 family proteins induces regression of solid tumours," Nature, Nature, vol. 435(7042), pages 677-681, June.
    • Handle: RePEc:nat:nature:v:435:y:2005:i:7042:d:10.1038_nature03579
    DOI: 10.1038/nature03579
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    Citations

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    Cited by:

    1. Florian J. Bock & Egor Sedov & Elle Koren & Anna L. Koessinger & Catherine Cloix & Désirée Zerbst & Dimitris Athineos & Jayanthi Anand & Kirsteen J. Campbell & Karen Blyth & Yaron Fuchs & Stephen W. G, 2021. "Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Hudie Wei & Haolan Wang & Genxin Wang & Lingzhi Qu & Longying Jiang & Shuyan Dai & Xiaojuan Chen & Ye Zhang & Zhuchu Chen & Youjun Li & Ming Guo & Yongheng Chen, 2023. "Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Andrea Lopez & Denis E. Reyna & Nadege Gitego & Felix Kopp & Hua Zhou & Miguel A. Miranda-Roman & Lars Ulrik Nordstrøm & Swathi-Rao Narayanagari & Ping Chi & Eduardo Vilar & Aristotelis Tsirigos & Evr, 2022. "Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Fengwei Li & Junjie Liu & Chao Liu & Ziyan Liu & Xiangda Peng & Yinyue Huang & Xiaoyu Chen & Xiangnan Sun & Sen Wang & Wei Chen & Dan Xiong & Xiaotong Diao & Sheng Wang & Jingjing Zhuang & Chuanliu Wu, 2024. "Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XL by engaging a single-residue discrepancy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Motohiro Sekiya & Kenta Kainoh & Takehito Sugasawa & Ryunosuke Yoshino & Takatsugu Hirokawa & Hiroaki Tokiwa & Shogo Nakano & Satoru Nagatoishi & Kouhei Tsumoto & Yoshinori Takeuchi & Takafumi Miyamot, 2021. "The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

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