Nature Communications (Mar 2017)
Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention
- Thomas Bohnacker,
- Andrea E. Prota,
- Florent Beaufils,
- John E. Burke,
- Anna Melone,
- Alison J. Inglis,
- Denise Rageot,
- Alexander M. Sele,
- Vladimir Cmiljanovic,
- Natasa Cmiljanovic,
- Katja Bargsten,
- Amol Aher,
- Anna Akhmanova,
- J. Fernando Díaz,
- Doriano Fabbro,
- Marketa Zvelebil,
- Roger L. Williams,
- Michel O. Steinmetz,
- Matthias P. Wymann
Affiliations
- Thomas Bohnacker
- Department of Biomedicine, University of Basel
- Andrea E. Prota
- Department of Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institut
- Florent Beaufils
- Department of Biomedicine, University of Basel
- John E. Burke
- Department of Biochemistry and Microbiology, University of Victoria
- Anna Melone
- Department of Biomedicine, University of Basel
- Alison J. Inglis
- MRC Laboratory of Molecular Biology
- Denise Rageot
- Department of Biomedicine, University of Basel
- Alexander M. Sele
- Department of Biomedicine, University of Basel
- Vladimir Cmiljanovic
- Department of Biomedicine, University of Basel
- Natasa Cmiljanovic
- Department of Biomedicine, University of Basel
- Katja Bargsten
- Department of Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institut
- Amol Aher
- Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht
- Anna Akhmanova
- Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht
- J. Fernando Díaz
- CIB Centro de Investigaciones Biológicas
- Doriano Fabbro
- PIQUR Therapeutics AG
- Marketa Zvelebil
- The Institute of Cancer Research
- Roger L. Williams
- MRC Laboratory of Molecular Biology
- Michel O. Steinmetz
- Department of Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institut
- Matthias P. Wymann
- Department of Biomedicine, University of Basel
- DOI
- https://doi.org/10.1038/ncomms14683
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 13
Abstract
Buparlisib/BKM120 is in phase 3 clinical trials as a phosphoinositide 3-kinase (PI3K) inhibitor. Here, Bohnackeret al. combine chemical biology and structural biology approaches to segregate BKM120’s biological actions, and suggest that it causes mitotic arrest predominantly by binding microtubules and disrupting their dynamics.
