dc.contributor.author |
Wang, Jia |
en |
dc.contributor.author |
Gong, Grace Qun |
en |
dc.contributor.author |
Zhou, Yan |
en |
dc.contributor.author |
Lee, Woo Jeong |
en |
dc.contributor.author |
Buchanan, Christina |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Rewcastle, Gordon |
en |
dc.contributor.author |
Kendall, Jackie Diane |
en |
dc.contributor.author |
Dickson, James |
en |
dc.contributor.author |
Flanagan, Jack |
en |
dc.contributor.author |
Shepherd, Peter Robin |
en |
dc.contributor.author |
Yang, De-Hua |
en |
dc.contributor.author |
Wang, Ming-Wei |
en |
dc.date.accessioned |
2018-10-26T03:40:28Z |
en |
dc.date.issued |
2018-11 |
en |
dc.identifier.issn |
1671-4083 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/43598 |
en |
dc.description.abstract |
The phosphatidylinositol 3-kinase (PI3K) pathway is involved in many cellular functions including cell growth, metabolism, and transformation. Hyperactivation of this pathway contributes to tumorigenesis, therefore, PI3K is a major target for anticancer drug discovery. Since the PI3Kα isoform is implicated mostly in cancer, we conducted a high-throughput screening (HTS) campaign using a 3-step PI3K homogenous time-resolved fluorescence assay against this isoform bearing the H1047R mutation. A total of 288,000 synthetic and natural product-derived compounds were screened and of which, we identified 124 initial hits that were further selected by considering the predicted binding mode, relationship to known pan-assay interference compounds and previous descriptions as a lipid kinase inhibitor. A total of 24 compounds were then tested for concentration-dependent responses. These hit compounds provide novel scaffolds that can potentially be optimized to create novel PI3K inhibitors. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Acta pharmacologica Sinica |
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.subject |
Humans |
en |
dc.subject |
Isoenzymes |
en |
dc.subject |
Protein Kinase Inhibitors |
en |
dc.subject |
Protein Binding |
en |
dc.subject |
Mutation |
en |
dc.subject |
Hydrogen Bonding |
en |
dc.subject |
High-Throughput Screening Assays |
en |
dc.subject |
Phosphatidylinositol 3-Kinases |
en |
dc.subject |
Molecular Docking Simulation |
en |
dc.title |
High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1038/s41401-018-0057-z |
en |
pubs.issue |
11 |
en |
pubs.begin-page |
1816 |
en |
pubs.volume |
39 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.end-page |
1822 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
747965 |
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 |
Molecular Medicine |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1745-7254 |
en |
pubs.record-created-at-source-date |
2018-07-12 |
en |
pubs.dimensions-id |
29991713 |
en |