dc.contributor.author |
Trinh, TN |
en |
dc.contributor.author |
McLaughlin, Eileen |
en |
dc.contributor.author |
Gordon, CP |
en |
dc.contributor.author |
Bernstein, IR |
en |
dc.contributor.author |
Pye, VJ |
en |
dc.contributor.author |
Redgrove, KA |
en |
dc.contributor.author |
McCluskey, A |
en |
dc.date.accessioned |
2017-06-28T02:55:47Z |
en |
dc.date.issued |
2017 |
en |
dc.identifier.citation |
Organic and Biomolecular Chemistry 15(14):3046-3059 2017 |
en |
dc.identifier.issn |
1477-0520 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/33811 |
en |
dc.description.abstract |
Leveraging our quinolone-1-(2H)-one based Hedgehog signalling pathway (HSP) inhibitors we have developed two new classes of HSP inhibitors based on: l-tryptophan and benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine. Synthesis of focused compound libraries identified six l-tryptophan based inhibitors, and two stimulators, of Gli at 10 μM compound concentration. 2,4-Dichloro-13 and indole 16 suppressed mRNA expression of Ptch1 in Shh LIGHT2 cells, with 13 suppressing and 16 stimulating Gli2 mRNA expression. Focused library development of the benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine scaffold afforded two sub-micro molar potent inhibitors of Gli expression with 5-methoxy-1H-indole-2-carboxylic acid benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amide 29 and 5-chloro-1H-indole-2-carboxylic acid benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amide 30 returning IC50 values of 0.5 and 0.24 μM, respectively. Neither 29 nor 30 acted directly on Smo with our data supporting inhibition of the HSP downstream of Smo. |
en |
dc.format.medium |
Print |
en |
dc.language |
eng |
en |
dc.publisher |
Royal Society of Chemistry |
en |
dc.relation.ispartofseries |
Organic and Biomolecular 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 |
Small molecule Hedgehog pathway antagonists |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1039/c6ob01959e |
en |
pubs.issue |
14 |
en |
pubs.begin-page |
3046 |
en |
pubs.volume |
15 |
en |
dc.rights.holder |
Copyright: Royal Society of Chemistry |
en |
dc.identifier.pmid |
28318003 |
en |
pubs.end-page |
3059 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
618645 |
en |
dc.identifier.eissn |
1477-0539 |
en |
pubs.record-created-at-source-date |
2017-06-28 |
en |
pubs.dimensions-id |
28318003 |
en |