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Vanadium Compounds as PTP Inhibitors

Irving, E; Stoker, AW; (2017) Vanadium Compounds as PTP Inhibitors. Molecules , 22 (12) , Article 2269. 10.3390/molecules22122269. Green open access

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Abstract

Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

Type: Article
Title: Vanadium Compounds as PTP Inhibitors
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/molecules22122269
Publisher version: http://dx.doi.org/10.3390/molecules22122269
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
Keywords: BMOV, PTP, cancer, diabetes, oxidovanadium, oxovanadium, protein tyrosine phosphatases, vanadate, vanadium
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10041042
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