Evaluation of the potential synergism of imatinib-related poly kinase inhibitors using growth factor stimulated proteoglycan synthesis as a model response

Bernard, Rebekah, Getachew R., Kamato D., Thach L., Osman N., Chan V., Zheng W. and Little P.J. (2016) Evaluation of the potential synergism of imatinib-related poly kinase inhibitors using growth factor stimulated proteoglycan synthesis as a model response. Journal of Pharmacy and Pharmacology, 68 3: 368-378. doi:10.1111/jphp.12530


Author Bernard, Rebekah
Getachew R.
Kamato D.
Thach L.
Osman N.
Chan V.
Zheng W.
Little P.J.
Title Evaluation of the potential synergism of imatinib-related poly kinase inhibitors using growth factor stimulated proteoglycan synthesis as a model response
Journal name Journal of Pharmacy and Pharmacology   Check publisher's open access policy
ISSN 2042-7158
0022-3573
Publication date 2016-03
Year available 2016
Sub-type Article (original research)
DOI 10.1111/jphp.12530
Open Access Status Not Open Access
Volume 68
Issue 3
Start page 368
End page 378
Total pages 11
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2017
Language eng
Formatted abstract
Introduction
Tyrosine kinase inhibitors were the first class of smart drugs being specifically designed to inhibit a disease causing target. There is a very important but unresolved question as whether or not the overall therapeutic role of an individual tinib results from an action at its primary target, a single most likely, tyrosine kinase, or from the combined or aggregate action at the multiple targets which each tinib addresses.

Methods
We selected a series of ten tinibs (gefitinib, sunitinib, lapatinib, erlotinib, imatinib, sorafenib, axitinib, vanitinib, bosutinib, dasatinib) with various known targets and investigated their activities in the inhibition of proteoglycan synthesis and GAG hyperelongation stimulated by a tyrosine kinase receptor agonist, platelet derived growth factor (PDGF) and for contrast, a serine/threonine kinase receptor agonist, TGF β and some downstream signalling pathways.

Results
The inhibitory activity varied from little to total inhibition. The actions of the tinibs were directed more towards inhibition of the tyrosine kinase, PDGF receptor signalling pathway compared to the TGF β.

Conclusion
There was no suggestion of any synergistic effect arising from inhibition of multiple kinases as the most potent compound, dasatinib, is known to inhibit the broadest spectrum of kinases.
Keyword Cell signalling
GAG hyperelongation
Platelet derived growth factor
Proteoglycan
Tinibs
Transforming growth factor-β
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Pharmacy Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 15 Mar 2016, 01:30:55 EST by System User on behalf of Learning and Research Services (UQ Library)