Prototyping kinase inhibitor-cytotoxin anticancer mutual prodrugs activated by tumour hypoxia: A chemical proof of concept study.

Sansom, Geraud N; Kirk, Nicholas S; Guise, Christopher P; Anderson, Robert F; Smaill, Jeff B; Patterson, Adam V; Kelso, Michael J

dc.contributor.author	Sansom, Geraud N
dc.contributor.author	Kirk, Nicholas S
dc.contributor.author	Guise, Christopher P
dc.contributor.author	Anderson, Robert F
dc.contributor.author	Smaill, Jeff B
dc.contributor.author	Patterson, Adam V
dc.contributor.author	Kelso, Michael J
dc.date.accessioned	2020-12-09T00:58:28Z
dc.date.available	2020-12-09T00:58:28Z
dc.date.issued	2019-5
dc.identifier.issn	0960-894X
dc.identifier.uri	http://hdl.handle.net/2292/53954
dc.description.abstract	Amide- and ester-linked kinase inhibitor-cytotoxin conjugates were rationally designed and synthesised as prototype hypoxia-activated anticancer mutual prodrugs. Chemical reduction of an aryl nitro trigger moiety was shown to initiate a spontaneous cyclisation/fragmentation reaction that simultaneously released the kinase inhibitor semaxanib (SU5416) and the amine- or alcohol-linked cytotoxin from the prodrugs. Preliminary cell testing and reduction potential measurements support optimisation of the compounds towards tumour-selective mutual prodrugs.
dc.format.medium	Print-Electronic
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartofseries	Bioorganic & medicinal chemistry letters
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.
dc.rights.uri	https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.subject	Cell Line, Tumor
dc.subject	Humans
dc.subject	Alcohols
dc.subject	Amines
dc.subject	Pyrroles
dc.subject	Indoles
dc.subject	Floxuridine
dc.subject	Antineoplastic Agents
dc.subject	Cytotoxins
dc.subject	Prodrugs
dc.subject	Protein Kinase Inhibitors
dc.subject	Drug Screening Assays, Antitumor
dc.subject	Cell Proliferation
dc.subject	Molecular Structure
dc.subject	Structure-Activity Relationship
dc.subject	Tumor Hypoxia
dc.subject	Proof of Concept Study
dc.subject	Science & Technology
dc.subject	Life Sciences & Biomedicine
dc.subject	Physical Sciences
dc.subject	Chemistry, Medicinal
dc.subject	Chemistry, Organic
dc.subject	Pharmacology & Pharmacy
dc.subject	Chemistry
dc.subject	Hypoxia
dc.subject	Mutual prodrug
dc.subject	Anticancer
dc.subject	Bioreductive activation
dc.subject	Sunitinib
dc.subject	Semaxinib
dc.subject	Floxuridine
dc.subject	4-Aminoaniline mustard
dc.subject	NITRO REDUCTION
dc.subject	PHASE-II
dc.subject	DESIGN
dc.subject	SU5416
dc.subject	INDOLIN-2-ONES
dc.subject	DERIVATIVES
dc.subject	DELIVERY
dc.subject	0302 Inorganic Chemistry
dc.subject	0304 Medicinal and Biomolecular Chemistry
dc.subject	0305 Organic Chemistry
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.title	Prototyping kinase inhibitor-cytotoxin anticancer mutual prodrugs activated by tumour hypoxia: A chemical proof of concept study.
dc.type	Journal Article
dc.identifier.doi	10.1016/j.bmcl.2019.03.015
pubs.issue	10
pubs.begin-page	1215
pubs.volume	29
dc.date.updated	2020-11-16T19:01:34Z
dc.rights.holder	Copyright: The author	en
pubs.author-url	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000463383800012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e41486220adb198d0efde5a3b153e7d
pubs.end-page	1219
pubs.publication-status	Published
dc.rights.accessrights	http://purl.org/eprint/accessRights/RestrictedAccess	en
pubs.subtype	Research Support, Non-U.S. Gov't
pubs.subtype	Journal Article
pubs.elements-id	766863
dc.identifier.eissn	1464-3405