Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

Xianming Deng, Nicolas Dzamko, Alan Prescott, Paul Davies, Qingsong Liu, Qingkai Yang, Jiing-Dwan Lee, Matthew P. Patricelli, Tyzoon K. Nomanbhoy, Dario R. Alessi, Nathanael S. Gray

    Research output: Contribution to journalArticle

    263 Citations (Scopus)

    Abstract

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. We employed a new, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor, LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces dephosphorylation of Ser910 and Ser935 and accumulation of LRRK2 within aggregate structures. LRRK2-IN-1 will serve as a versatile tool to pharmacologically interrogate LRRK2 biology and study its role in Parkinson's disease.

    Original languageEnglish
    Pages (from-to)203-205
    Number of pages3
    JournalNature Chemical Biology
    Volume7
    Issue number4
    DOIs
    Publication statusPublished - Apr 2011

    Keywords

    • CYTOPLASMIC LOCALIZATION
    • 14-3-3 BINDING
    • MUTATIONS
    • MAP

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