dc.contributor.author |
Huttunen, KM |
en |
dc.contributor.author |
Gynther, M |
en |
dc.contributor.author |
Huttunen, J |
en |
dc.contributor.author |
Puris, E |
en |
dc.contributor.author |
Spicer, Julie |
en |
dc.contributor.author |
Denny, William |
en |
dc.date.accessioned |
2017-04-06T04:41:01Z |
en |
dc.date.issued |
2016-06-23 |
en |
dc.identifier.citation |
Journal of Medicinal Chemistry 59(12):5740-5751 23 Jun 2016 |
en |
dc.identifier.issn |
0022-2623 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/32489 |
en |
dc.description.abstract |
The l-type amino acid transporter 1 (LAT1) is a transmembrane protein carrying bulky and neutral amino acids into cells. LAT1 is overexpressed in several types of tumors, and its inhibition can result in reduced cancer cell growth. However, known LAT1 inhibitors lack selectivity over other transporters. In the present study, we designed and synthesized a novel selective LAT1 inhibitor (1), which inhibited the uptake of LAT1 substrate, l-leucin as well as cell growth. It also significantly potentiated the efficacy of bestatin and cisplatin even at low concentrations (25 μM). Inhibition was slowly reversible, as the inhibitor was able to be detached from the cell surface and blood-brain barrier. Moreover, the inhibitor was metabolically stable and selective toward LAT1. Since the inhibitor was readily accumulated into the prostate after intraperitoneal injection to the healthy mice, this compound may be a promising agent or adjuvant especially for the treatment of prostate cancer. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Journal of 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 |
A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/acs.jmedchem.6b00190 |
en |
pubs.issue |
12 |
en |
pubs.begin-page |
5740 |
en |
pubs.volume |
59 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
dc.identifier.pmid |
27253989 |
en |
pubs.end-page |
5751 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
531473 |
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 |
1520-4804 |
en |
pubs.record-created-at-source-date |
2017-04-06 |
en |
pubs.dimensions-id |
27253989 |
en |