Inhibition of the Pore-forming Protein Perforin by a Series of Aryl-Substituted Isobenzofuran-1(3H)-ones

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dc.contributor.author Miller, Christian en
dc.contributor.author Spicer, JA en
dc.contributor.author Huttunen, KM en
dc.contributor.author Denny, William en
dc.contributor.author Ciccone, A en
dc.contributor.author Browne, KA en
dc.contributor.author Trapani, JA en
dc.date.accessioned 2012-03-25T21:10:50Z en
dc.date.issued 2011-12-07 en
dc.identifier.citation Bioorganic & Medicinal Chemistry 20 07 Dec 2011 en
dc.identifier.issn 0968-0896 en
dc.identifier.uri http://hdl.handle.net/2292/15226 en
dc.description.abstract An aryl-substituted isobenzofuran-1(3H)-one lead compound was identified from a high throughput screen designed to find inhibitors of the lymphocyte pore-forming protein perforin. A series of analogs were then designed and prepared, exploring structure–activity relationships through variation of 2-thioxoimidazolidin-4-one and furan subunits on an isobenzofuranone core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 natural killer effector cells was determined. Several compounds showed excellent activity at concentrations that were non-toxic to the killer cells. This series represents a significant improvement on previous classes of compounds, being substantially more potent and largely retaining activity in the presence of serum. en
dc.publisher Elsevier en
dc.relation.ispartofseries Bioorganic & Medicinal Chemistry en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: http://www.sherpa.ac.uk/romeo/issn/0968-0896/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Inhibition of the Pore-forming Protein Perforin by a Series of Aryl-Substituted Isobenzofuran-1(3H)-ones en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.bmc.2011.12.011 en
pubs.volume 20 en
dc.rights.holder Copyright: Elsevier en
dc.identifier.pmid 22244072 en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 268249 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2012-01-09 en
pubs.dimensions-id 22244072 en


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