dc.contributor.author |
Frederick, R |
en |
dc.contributor.author |
Denny, William |
en |
dc.date.accessioned |
2011-11-17T17:24:35Z |
en |
dc.date.issued |
2008 |
en |
dc.identifier.citation |
Journal of Chemical Information and Modeling 48(3):629-638 2008 |
en |
dc.identifier.issn |
1549-9596 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/9258 |
en |
dc.description.abstract |
The p110α isoform of the class IA PI3Ks was recently genetically validated as a promising target for anticancer therapy. However, up to now, only one compound (PIK75 = 1) has been reported as a very potent and selective inhibitor of this isoform. The lack of a 3D structure for this enzyme has clearly hindered the discovery of new p110α selective compounds. In view of this, we combined target-based (homology modeling) and ligand-based (3D-QSAR) approaches in an attempt to define an integrated interaction model for p110α inhibition. Twenty-five analogues of 1 were docked within the putative p110α binding site, and the molecular alignment generated was subsequently used to derive QSAR models based on scoring function, free energy of binding, CoMFA. and CoMSIA. The predictive power of these models was then analyzed using a challenging test set of 5 compounds. CoMSIA, and particularly CoMFA, models were found to outperform the other methods, predicting accurately the potency of 100% of the compounds in the test set, thereby validating our p110α homology model for use in further drug development. |
en |
dc.language |
EN |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Journal of Chemical Information and Modeling |
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. Details obtained from
http://www.sherpa.ac.uk/romeo/issn/1549-9596/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
CANCER-SPECIFIC MUTATIONS |
en |
dc.subject |
BIOLOGICAL EVALUATION |
en |
dc.subject |
3-KINASE |
en |
dc.subject |
DERIVATIVES |
en |
dc.subject |
KINASE |
en |
dc.subject |
INSIGHTS |
en |
dc.subject |
PATHWAY |
en |
dc.subject |
GROWTH |
en |
dc.title |
Phosphoinositide-3-kinases (PI3Ks): Combined comparative modeling and 3D-QSAR to rationalize the inhibition of p110±. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/ci700348m |
en |
pubs.issue |
3 |
en |
pubs.begin-page |
629 |
en |
pubs.volume |
48 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
dc.identifier.pmid |
18275176 |
en |
pubs.end-page |
638 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
79522 |
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 |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
18275176 |
en |