dc.contributor.author |
Spicer, Julie |
en |
dc.contributor.author |
Huttunen, KM |
en |
dc.contributor.author |
Miller, Christian |
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.contributor.editor |
Janda, KD |
en |
dc.date.accessioned |
2012-06-12T22:34:50Z |
en |
dc.date.issued |
2011-12-22 |
en |
dc.identifier.citation |
Bioorganic and Medicinal Chemistry 20(3):1319-1336 22 Dec 2011 |
en |
dc.identifier.issn |
0968-0896 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/18963 |
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. |
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.issue |
3 |
en |
pubs.begin-page |
1319 |
en |
pubs.volume |
20 |
en |
dc.rights.holder |
Copyright: Elsevier |
en |
pubs.end-page |
1336 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
310658 |
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 |
dc.identifier.eissn |
1464-3391 |
en |
pubs.record-created-at-source-date |
2012-03-05 |
en |