Organophosphorus Compounds: Intervention in Mechanisms of Signal Transduction Relevant to Proliferative, Immunological and Circulatory Disorders
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-α (TNF-α). Reported also are inhibitors of the ectoenzymes aminopeptidase N, aminopeptidase A and dipeptidyl peptidase IV, the proteolytic enzyme thrombin, ligands to “apoptosis-receptors” and γδ 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.
Document Type: Research Article
Affiliations: Institute for Health Research and Policy, London Metropolitan University, 166-220 Holloway Road London, UK N7 8DB.
Publication date: September 1, 2008
More about this publication?
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.