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

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 K. Joseph, Shinichi Kitada, Stanley J. Korsmeyer, Aaron R. Kunzer, Anthony Letai, Chi Li, Michael J. Mitten, David G. Nettesheim, ShiChung Ng, Paul M. Nimmer, Jacqueline M. O'Connor, Anatol Oleksijew, Andrew M. Petros, John C. Reed, Wang Shen, Stephen K. Tahir, Craig B. Thompson, Kevin J. Tomaselli, Baole Wang, Michael D. Wendt, Haichao Zhang, Stephen W. Fesik () and Saul H. Rosenberg ()
Additional contact information
Tilman Oltersdorf: Idun Pharmaceuticals
Steven W. Elmore: Abbott Laboratories
Alexander R. Shoemaker: Abbott Laboratories
Robert C. Armstrong: Idun Pharmaceuticals
David J. Augeri: Abbott Laboratories
Barbara A. Belli: Idun Pharmaceuticals
Milan Bruncko: Abbott Laboratories
Thomas L. Deckwerth: Idun Pharmaceuticals
Jurgen Dinges: Abbott Laboratories
Philip J. Hajduk: Abbott Laboratories
Mary K. Joseph: Abbott Laboratories
Shinichi Kitada: The Burnham Institute
Stanley J. Korsmeyer: Harvard Medical School
Aaron R. Kunzer: Abbott Laboratories
Anthony Letai: Dana-Farber Cancer Institute
Chi Li: University of Pennsylvania
Michael J. Mitten: Abbott Laboratories
David G. Nettesheim: Abbott Laboratories
ShiChung Ng: Abbott Laboratories
Paul M. Nimmer: Abbott Laboratories
Jacqueline M. O'Connor: Abbott Laboratories
Anatol Oleksijew: Abbott Laboratories
Andrew M. Petros: Abbott Laboratories
John C. Reed: The Burnham Institute
Wang Shen: Abbott Laboratories
Stephen K. Tahir: Abbott Laboratories
Craig B. Thompson: University of Pennsylvania
Kevin J. Tomaselli: Idun Pharmaceuticals
Baole Wang: Abbott Laboratories
Michael D. Wendt: Abbott Laboratories
Haichao Zhang: Abbott Laboratories
Stephen W. Fesik: Abbott Laboratories
Saul H. Rosenberg: Abbott Laboratories

Nature, 2005, vol. 435, issue 7042, 677-681

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.

Date: 2005
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DOI: 10.1038/nature03579

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