dc.contributor.author |
Choi, Peter |
en |
dc.contributor.author |
Cooper, E |
en |
dc.contributor.author |
Schweder, Patrick |
en |
dc.contributor.author |
Mee, E |
en |
dc.contributor.author |
Faull, Richard |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Dragunow, Michael |
en |
dc.contributor.author |
Park, In |
en |
dc.contributor.author |
Jose, Jiney |
en |
dc.date.accessioned |
2019-10-01T10:57:17Z |
en |
dc.date.issued |
2019-09-15 |
en |
dc.identifier.issn |
0960-894X |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/48221 |
en |
dc.description.abstract |
We describe the synthesis of drug-dye conjugate 1 between anaplastic lymphoma kinase inhibitor Crizotinib and heptamethine cyanine dye IR-786. The drug-dye conjugate 1 was evaluated in three different patient-derived glioblastoma cell lines and showed potent cytotoxic activity with nanomolar potency (EC50: 50.9 nM). We also demonstrate evidence for antiproliferative activity of 1 with single digit nanomolar potency (IC50: 4.7 nM). Furthermore, the cytotoxic effects conveyed a dramatic, 110-fold improvement over Crizotinib. This improvement was even more pronounced (492-fold) when 1 was combined with Temozolomide, the standard drug for treatment for glioblastoma. This work lays the foundation for future exploration of similar tyrosine kinase inhibitor drug-dye conjugates for the treatment of glioblastoma. |
en |
dc.publisher |
Elsevier |
en |
dc.relation.ispartofseries |
Bioorganic and Medicinal Chemistry Letters |
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 |
The synthesis of a novel Crizotinib heptamethine cyanine dye conjugate that potentiates the cytostatic and cytotoxic effects of Crizotinib in patient-derived glioblastoma cell lines |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bmcl.2019.07.051 |
en |
pubs.issue |
18 |
en |
pubs.begin-page |
2617 |
en |
pubs.volume |
29 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.end-page |
2621 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Letter |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
778856 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Anatomy and Medical Imaging |
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 |
2019-08-12 |
en |
pubs.online-publication-date |
2019-07-29 |
en |
pubs.dimensions-id |
31378572 |
en |