dc.contributor.author |
Hay, Michael |
en |
dc.contributor.author |
Turcotte, S |
en |
dc.contributor.author |
Flanagan, Jack |
en |
dc.contributor.author |
Bonnet, M |
en |
dc.contributor.author |
Chan, DA |
en |
dc.contributor.author |
Sutphin, PD |
en |
dc.contributor.author |
Nguyen, P |
en |
dc.contributor.author |
Giaccia, AJ |
en |
dc.contributor.author |
Denny, William |
en |
dc.date.accessioned |
2011-11-17T17:12:11Z |
en |
dc.date.accessioned |
2012-01-30T02:22:48Z |
en |
dc.date.issued |
2010 |
en |
dc.identifier.citation |
Journal of Medicinal Chemistry 53(2):787-797 2010 |
en |
dc.identifier.issn |
0022-2623 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/10798 |
en |
dc.description.abstract |
Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different chemical features to potency illustrates a region, adjacent to the pyridyl ring, with potential for further development. Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC. |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Journal of Medicinal Chemistry |
en |
dc.relation.replaces |
http://hdl.handle.net/2292/9206 |
en |
dc.relation.replaces |
2292/9206 |
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/0022-2623/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient Renal Cell Carcinoma cells by inducing autophagic cell death |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/jm901457w |
en |
pubs.issue |
2 |
en |
pubs.begin-page |
787 |
en |
pubs.volume |
53 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
dc.identifier.pmid |
19994864 |
en |
pubs.end-page |
797 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
99936 |
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 |
Pharmacology |
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 |
2010-09-01 |
en |
pubs.dimensions-id |
19994864 |
en |