Organophosphorus compounds: intervention in mechanisms of signal transduction relevant to proliferative, immunological and circulatory disorders

Wardle, Nicholas J., Bligh, S.W. Annie and Hudson, H.R. (2008) Organophosphorus compounds: intervention in mechanisms of signal transduction relevant to proliferative, immunological and circulatory disorders. Current Medicinal Chemistry, 15. pp. 2230-2257. ISSN 0929-8673

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Abstract

Literature publications reporting the development of organophosphorus compounds, targeting aspects of signal transduction to the titled therapeutic ends, are reviewed. With respect to extracellular targets, the development of ligands to purinergic (P2), and endothelial differentiation-gene receptors (of S1P- and LPA-receptor subtypes) is charted, along with inhibitors of the production and release of tumour necrosis factor-alpha (TNF-alpha). Reported also are inhibitors of the ectoenzymes aminopeptidase N, aminopeptidase A and dipeptidyl peptidase IV, the proteolytic enzyme thrombin, ligands to "apoptosis-receptors" and gammadelta T-cell activators. In addition, disruption of intracellular signalling chains mediated through reversible coupling of proteins via phosphorylation of Tyr residues and docking of pTyr residues in SH2-binding domains is covered. In particular, the development of ligands to SH2-binding domains in tyrosine kinases Src and lck, adaptor protein Grb2, and also ZAP70 protein are reported along with inhibitors to relevant phosphatases. SAR studies of ligands to Ins(1,4,5)-P3- and ryanodine-type receptors of intracellular Ca2+-storage organelles are described including analogues to secondary messengers cyclic-ADP-ribose (cADPR) and myo-inositol-1,4,5-triphosphate. Inhibitors of phosphatidyl inositol 3-kinase (PI3K) and sphingomyelinase are also reported, as are inhibitors of farnesyl transferase, the enzyme involved in protein-prenylation.

Item Type: Article
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Rachel Wheelhouse
Date Deposited: 25 Feb 2013 13:22
Last Modified: 25 Feb 2013 13:22
URI: http://westminsterresearch.wmin.ac.uk/id/eprint/12165

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