Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors.

Hicks, Kevin; Siim, BG; Jaiswal, Jagdish; Pruijn, Frederik; Fraser, AM; Patel, R; Hogg, A; Liyanage, HD; Dorie, MJ; Brown, JM; Denny, William; Hay, Michael; Wilson, William

dc.contributor.author	Hicks, Kevin	en
dc.contributor.author	Siim, BG	en
dc.contributor.author	Jaiswal, Jagdish	en
dc.contributor.author	Pruijn, Frederik	en
dc.contributor.author	Fraser, AM	en
dc.contributor.author	Patel, R	en
dc.contributor.author	Hogg, A	en
dc.contributor.author	Liyanage, HD	en
dc.contributor.author	Dorie, MJ	en
dc.contributor.author	Brown, JM	en
dc.contributor.author	Denny, William	en
dc.contributor.author	Hay, Michael	en
dc.contributor.author	Wilson, William	en
dc.coverage.spatial	United States	en
dc.date.accessioned	2011-11-17T17:24:01Z	en
dc.date.issued	2010-10	en
dc.identifier.citation	Clinical Cancer Research 16(20):4946-4957 Oct 2010	en
dc.identifier.issn	1078-0432	en
dc.identifier.uri	http://hdl.handle.net/2292/9255	en
dc.description.abstract	Tirapazamine (TPZ) has attractive features for targeting hypoxic cells in tumors but has limited clinical activity, in part because of poor extravascular penetration. Here, we identify improved TPZ analogues by using a spatially resolved pharmacokinetic/pharmacodynamic (SR-PKPD) model that considers tissue penetration explicitly during lead optimization.	en
dc.language	eng	en
dc.publisher	American Association for Cancer Research	en
dc.relation.ispartofseries	Clinical Cancer Research	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/1078-0432/	en
dc.rights.uri	https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm	en
dc.subject	Algorithms	en
dc.subject	Animals	en
dc.subject	Antineoplastic Agents	en
dc.subject	Cell Hypoxia	en
dc.subject	HT29 Cells	en
dc.subject	Humans	en
dc.subject	Male	en
dc.subject	Mice	en
dc.subject	Mice, Nude	en
dc.subject	Models, Biological	en
dc.subject	Neoplasms	en
dc.subject	Oxygen	en
dc.subject	Radiation-Sensitizing Agents	en
dc.subject	Rats	en
dc.subject	Rats, Sprague-Dawley	en
dc.subject	Triazines	en
dc.subject	Xenograft Model Antitumor Assays	en
dc.title	Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors.	en
dc.type	Journal Article	en
dc.identifier.doi	10.1158/1078-0432.CCR-10-1439	en
pubs.issue	20	en
pubs.begin-page	4946	en
pubs.volume	16	en
dc.rights.holder	Copyright: American Association for Cancer Research	en
dc.identifier.pmid	20732963	en
pubs.end-page	4957	en
dc.rights.accessrights	http://purl.org/eprint/accessRights/RestrictedAccess	en
pubs.subtype	Article	en
pubs.elements-id	157300	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.pii	1078-0432.CCR-10-1439	en
pubs.record-created-at-source-date	2011-11-17	en
pubs.dimensions-id	20732963	en