Inflammation
Development of anti-inflammatory agents
With Professor David R. Greaves (Sir William Dunn School of Pathology, University of Oxford)
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Chronic inflammation is an underlying cause of many prevalent diseases such as diabetes and cardiovascular disease, but few available treatments aim to reduce the inflammatory response in these conditions. In collaboration with Professor David Greaves at the Sir William Dunn School of Pathology, we are developing and characterising novel ligands for G protein-coupled receptors involved in regulating inflammation.

Using virtual screening we have identified a new family of highly selective cannabinoid receptor 2 agonists which can be used to activate the anti-inflammatory properties of the cannabinoid system, while sparing the CNS.1 We are also developing chemical tools to target poorly characterised immunometabolic receptors, such as the fatty acid receptor GPR84.2 High quality chemical probes will enable the validation of these receptors as new targets for treatments of inflammatory metabolic disease.

References
(1) Gianella-Borradori, M.; Christou, I.; Bataille, C. J. R.; Cross, R. L.; Wynne, G. M.; Greaves, D. R.; Russell, A. J. Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. Bioorg. Med. Chem. 2015, 23, 241-263.
(2) Taylor, L.; Christou, I.; Kapellos, T. S.; Buchan, A.; Brodermann, M. H.; Gianella-Borradori, M.; Russell, A.; Iqbal, A. J.; Greaves, D. R. Primary macrophage chemotaxis induced by cannabinoid receptor 2 agonists occurs independently of the CB2 receptor. Scientific Rep. 2015, 5, 10682.
(3) Recio, C., Lucy, D., Purvis, G.S.D., Iveson, P., Zeboudj, L., Iqbal, A.J., Lin, D., O'Callaghan, C., Davison, L., Griesbach, E., Russell, A.J., Wynne, G.M., Dib, L., Monaco, C., and Greaves, D.R. Activation of the Immune-Metabolic Receptor GPR84 Enhances Inflammation and Phagocytosis in Macrophages. Front. Immunol. 2018, 9:1419.