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

Bernard, Rebekah; Getachew, Robel; Kamato, Danielle; Thach, Lyna; Osman, Narin; Chan, Vincent; Zheng, Wenhua; Little, Peter J.

doi:10.1111/jphp.12530

Cited by 9 publications

(9 citation statements)

References 52 publications

(78 reference statements)

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“…The therapeutic rational for these studies is that there is the potential for a specific kinase inhibitor or an inhibitor of multiple kinases (Bernard et al, 2016) to be a therapeutic agent for the reduction in atherosclerosis and the prevention of cardiovascular disease (Little et al, 2007). It can also be mentioned that there is an alternative approach of targeting GAG chain biosynthesis which is to use GAG-directed antibodies which block the ionic interaction between GAG chains and ApoB100; the veracity of this approach has recently been demonstrated in a mouse model of intimal hyperplasia where the accelerated atherosclerosis was shown to be due to lipoprotein binding to modified proteoglycans and the interaction and hence the atherosclerosis could be blocked by GAG directed antibodies (Kijani et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2

Rostam

Shajimoon

Kamato

et al. 2018

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2

Rostam

Shajimoon

Kamato

et al. 2018

J Pharmacol Exp Ther

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“…Tinibs act by binding and competing with ATP on the catalytic domain of tyrosine kinases and ultimately block the autophosphorylation of receptor-tyrosine kinases and downstream signaling. Tinibs block a small number of different TKs and their clinical action might arise from these multiple targets 139 . An array of new drugs are biologicals including monoclonal antibodies (“mabs”) such as trastuzumab, which is directed against the ERBB2 receptor extracellular domain and interferes with the PI3K-AKT -FOXO3a-FOXM1 axis signaling.…”

Section: Current Anti-cancer Drugs Impacting Foxo Functions and Signamentioning

confidence: 99%

FOXO Signaling Pathways as Therapeutic Targets in Cancer

et al. 2017

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Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers. During apoptosis, FOXOs are involved in mitochondria-dependent and -independent processes triggering the expression of death receptor ligands like Fas ligand, TNF apoptosis ligand and Bcl‑XL, bNIP3, Bim from Bcl-2 family members. Different types of growth factors like insulin play a vital role in the regulation of FOXOs. The most important pathway interacting with FOXO in different types of cancers is the PI3K/AKT pathway. Some other important pathways such as the Ras-MEK-ERK, IKK and AMPK pathways are also associated with FOXOs in tumorigenesis. Therapeutically targeting the FOXO signaling pathway(s) could lead to the discovery and development of efficacious agents against some cancers, but this requires an enhanced understanding and knowledge of FOXO transcription factors and their regulation and functioning. This review focused on the current understanding of cell biology of FOXO transcription factors which relates to their potential role as targets for the treatment and prevention of human cancers. We also discuss drugs which are currently being used for cancer treatment along with their target pathways and also point out some potential drawbacks of those drugs, which further signifies the need for development of new drug strategies in the field of cancer treatment.

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“…This direction, as we have recently described (Kamato et al 2015b;Bernard et al 2016) will benefit from the development of new pharmacological tools. This area poses an interesting question as to the role of G proteins in transactivation and would require a full evaluation of the role of G proteins in GPCR transactivation signalling to define these pathways further.…”

Section: Dual Gpcr Transactivation and The Effects On Vascular Smoothmentioning

confidence: 99%

Insights into cellular signalling by G protein coupled receptor transactivation of cell surface protein kinase receptors

Chaplin

Thach

Hollenberg

et al. 2017

J. Cell Commun. Signal.

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G protein coupled receptor (GPCR) signalling is mediated by transactivation independent and transactivation dependent pathways. GPCRs transactivate protein tyrosine kinase receptors (PTKRs) and protein serine/threonine kinase receptors (PS/TKR). Since the initial observations of transactivation dependent signalling, there has been an effort to understand the mechanisms behind this phenomena. GPCR signalling has evolved to include biased signalling. Biased signalling, whereby selected ligands can activate the same GPCR that can generate multiple signals, but drive only a unique response. To date, there has been no focus on the ability of biased agonists to activate the PTKR and PS/TKR transactivation pathways differentially. As such, this represents a novel direction for future research. This review will discuss the main mechanisms of GPCR mediated receptor transactivation and the pathways involved in intracellular responses.

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

Abstract: 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.

Cited by 9 publications

References 52 publications

Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2

Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2

FOXO Signaling Pathways as Therapeutic Targets in Cancer

Insights into cellular signalling by G protein coupled receptor transactivation of cell surface protein kinase receptors

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