Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2 (original) (raw)

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Acknowledgements

We wish to thank staff at the National Centre for Protein Kinase Profiling (http://www.kinase-screen.mrc.ac.uk) for undertaking Dundee kinase specificity screening, F. Hentati (Institut National de Neurologie, Tunisia) and A. Reith (GlaxoSmithKline Pharmaceuticals Research and Development) for providing EBV immortalized human lymphoblastoid cells, P. Bamborough (GlaxoSmithKline Pharmaceuticals Research and Development) for providing LRRK2 homology model and the antibody purification teams (Division of Signal Transduction Therapy (DSTT), University of Dundee) coordinated by H. McLauchlan and J. Hastie for generation of antibodies. This work was supported by US National Institutes of Health grant P41 GM079575-03 (N.S.G.), the Medical Research Council Technology Industry Collaboration Award and a National Health and Medical Research Council postdoctoral fellowship (N.D.), the Medical Research Council (D.R.A.), the Michael J. Fox Foundation for Parkinson's Disease Research (D.R.A.), the pharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA and Pfizer) (D.R.A.), the US National Institutes of Health grants CA079871 and CA114059 (J.-D.L.) and funds from the Tobacco-Related Disease Research Program of the University of California, 19XT-0084, (J.-D.L.).

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Author notes

  1. Xianming Deng and Nicolas Dzamko: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
    Xianming Deng, Qingsong Liu & Nathanael S Gray
  2. Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    Xianming Deng, Qingsong Liu & Nathanael S Gray
  3. MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, Scotland
    Nicolas Dzamko, Paul Davies & Dario R Alessi
  4. Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland
    Alan Prescott
  5. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA
    Qingkai Yang & Jiing-Dwan Lee
  6. ActivX Biosciences, La Jolla, California, USA
    Matthew P Patricelli & Tyzoon K Nomanbhoy

Authors

  1. Xianming Deng
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  2. Nicolas Dzamko
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  3. Alan Prescott
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  4. Paul Davies
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  5. Qingsong Liu
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  6. Qingkai Yang
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  7. Jiing-Dwan Lee
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  8. Matthew P Patricelli
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  9. Tyzoon K Nomanbhoy
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  10. Dario R Alessi
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  11. Nathanael S Gray
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Contributions

N.S.G. conceived and directed the chemistry effort. X.D. performed the chemical synthesis and structure-activity relationship analysis. D.R.A. conceived and directed the biology effort. N.D. performed the biology experimental research with assistance from A.P. (confocal microscopy and live cell imaging). P.D. performed the SHSY5Y experiment. Q.L. performed the modeling study. Q.Y. and J.-D.L. performed the MAPK7 cellular assay. M.P.P. and T.K.N. performed the KiNativ selectivity profiling and data analysis. X.D., N.D., D.R.A. and N.S.G. co-wrote the paper. All authors read and edited the manuscript.

Corresponding authors

Correspondence toDario R Alessi or Nathanael S Gray.

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Competing interests

M.P.P. and T.K.N. are employees of ActivX Biosciences.

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Deng, X., Dzamko, N., Prescott, A. et al. Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2.Nat Chem Biol 7, 203–205 (2011). https://doi.org/10.1038/nchembio.538

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