• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Discovery of potent inhibitors of the lysophospholipase autotaxin.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Shah, P
    Cheasty, A
    Foxton, C
    Raynham, T
    Farooq, M
    Gutierrez, I
    Lejeune, A
    Pritchard, M
    Turnbull, A
    Pang, L
    Owen, P
    Boyd, S
    Stowell, Alexandra I J
    Jordan, Allan M
    Hamilton, Niall M
    Hitchin, James R
    Stockley, M
    MacDonald, E
    Quesada, M
    Trivier, E
    Skeete, J
    Ovaa, H
    Moolenaar, W
    Ryder, H
    Show allShow less
    Affiliation
    Cancer Research Technology, Discovery Laboratories, Babraham Research Campus, Cambridge CB22 3AT, UK
    Issue Date
    2016-10-14
    
    Metadata
    Show full item record
    Abstract
    The autotoxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active of ATX together with the occupying the LPA 'exit' channel.
    Citation
    Discovery of potent inhibitors of the lysophospholipase autotaxin. 2016 Bioorg. Med. Chem. Lett.
    Journal
    Bioorganic & Medicinal Chemistry Letters
    URI
    http://hdl.handle.net/10541/620020
    DOI
    10.1016/j.bmcl.2016.10.036
    PubMed ID
    27780639
    Type
    Article
    ISSN
    1464-3405
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.bmcl.2016.10.036
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Discovery, Structure-Activity Relationship, and Binding Mode of an Imidazo[1,2-a]pyridine Series of Autotaxin Inhibitors.
    • Authors: Joncour A, Desroy N, Housseman C, Bock X, Bienvenu N, Cherel L, Labeguere V, Peixoto C, Annoot D, Lepissier L, Heiermann J, Hengeveld WJ, Pilzak G, Monjardet A, Wakselman E, Roncoroni V, Le Tallec S, Galien R, David C, Vandervoort N, Christophe T, Conrath K, Jans M, Wohlkonig A, Soror S, Steyaert J, Touitou R, Fleury D, Vercheval L, Mollat P, Triballeau N, van der Aar E, Brys R, Heckmann B
    • Issue date: 2017 Sep 14
    • Discovery and synthetic optimization of a novel scaffold for hydrophobic tunnel-targeted autotaxin inhibition.
    • Authors: Ragle LE, Palanisamy DJ, Joe MJ, Stein RS, Norman DD, Tigyi G, Baker DL, Parrill AL
    • Issue date: 2016 Oct 1
    • Hits of a high-throughput screen identify the hydrophobic pocket of autotaxin/lysophospholipase D as an inhibitory surface.
    • Authors: Fells JI, Lee SC, Fujiwara Y, Norman DD, Lim KG, Tsukahara R, Liu J, Patil R, Miller DD, Kirby RJ, Nelson S, Seibel W, Papoian R, Parrill AL, Baker DL, Bittman R, Tigyi G
    • Issue date: 2013 Sep
    • Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis.
    • Authors: Black KE, Berdyshev E, Bain G, Castelino FV, Shea BS, Probst CK, Fontaine BA, Bronova I, Goulet L, Lagares D, Ahluwalia N, Knipe RS, Natarajan V, Tager AM
    • Issue date: 2016 Jun
    • Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis.
    • Authors: Gotoh M, Fujiwara Y, Yue J, Liu J, Lee S, Fells J, Uchiyama A, Murakami-Murofushi K, Kennel S, Wall J, Patil R, Gupte R, Balazs L, Miller DD, Tigyi GJ
    • Issue date: 2012 Feb
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.