• 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

    Cell-active small molecule inhibitors of the DNA-damage repair enzyme poly(ADP-ribose) glycohydrolase (PARG): discovery and optimization of orally bioavailable quinazolinedione sulphonamides.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Waszkowycz, Bohdan
    Smith, Kate M
    McGonagle, Alison E
    Jordan, Allan M
    Acton, Ben
    Fairweather, Emma E
    Griffiths, Louise A
    Hamilton, Niall M
    Hamilton, Nicola S
    Hitchin, James R
    Hutton, Colin P
    James, Dominic I
    Jones, CD
    Jones, Stuart
    Mould, Daniel P
    Small, Helen F
    Stowell, Alexandra I J
    Tucker, JA
    Waddell, Ian D
    Ogilvie, Donald J
    Show allShow less
    Affiliation
    Cancer Research UK Manchester Institute , The University of Manchester , Alderley Park , Maccelsfield SK10 4TG
    Issue Date
    2018
    
    Metadata
    Show full item record
    Abstract
    DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors.
    Citation
    Waszkowycz B, Smith KM, McGonagle AE, Jordan AM, Acton B, Fairweather EE, et al. Cell-active small molecule inhibitors of the DNA-damage repair enzyme poly(ADP-ribose) glycohydrolase (PARG): discovery and optimization of orally bioavailable quinazolinedione sulphonamides. J Med Chem. 2018 Nov 19.
    Journal
    J Med Chem
    URI
    http://hdl.handle.net/10541/621386
    DOI
    10.1021/acs.jmedchem.8b01407
    PubMed ID
    30403352
    Additional Links
    https://dx.doi.org/10.1021/acs.jmedchem.8b01407
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1021/acs.jmedchem.8b01407
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Targeting poly(ADP-ribose) glycohydrolase to draw apoptosis codes in cancer.
    • Authors: Tanuma SI, Shibui Y, Oyama T, Uchiumi F, Abe H
    • Issue date: 2019 Sep
    • Targeting SARS-CoV-2 Nsp3 macrodomain structure with insights from human poly(ADP-ribose) glycohydrolase (PARG) structures with inhibitors.
    • Authors: Brosey CA, Houl JH, Katsonis P, Balapiti-Modarage LPF, Bommagani S, Arvai A, Moiani D, Bacolla A, Link T, Warden LS, Lichtarge O, Jones DE, Ahmed Z, Tainer JA
    • Issue date: 2021 Aug
    • Design and synthesis of phenolic hydrazide hydrazones as potent poly(ADP-ribose) glycohydrolase (PARG) inhibitors.
    • Authors: Islam R, Koizumi F, Kodera Y, Inoue K, Okawara T, Masutani M
    • Issue date: 2014 Aug 15
    • Androgen Receptor and Poly(ADP-ribose) Glycohydrolase Inhibition Increases Efficiency of Androgen Ablation in Prostate Cancer Cells.
    • Authors: Zhang M, Lai Y, Vasquez JL, James DI, Smith KM, Waddell ID, Ogilvie DJ, Liu Y, Agoulnik IU
    • Issue date: 2020 Mar 2
    • Structures of the human poly (ADP-ribose) glycohydrolase catalytic domain confirm catalytic mechanism and explain inhibition by ADP-HPD derivatives.
    • Authors: Tucker JA, Bennett N, Brassington C, Durant ST, Hassall G, Holdgate G, McAlister M, Nissink JW, Truman C, Watson M
    • Issue date: 2012
    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.