The Drug Discovery Group brings together scientific expertise in a broad range of areas, from medicinal chemistry to systems biology and pharmacology:
I. Medicinal chemistry
We take a variety of approaches to access new areas of chemical space – from the rational design of small molecular probes and inhibitors for therapeutically interesting targets (e.g., glycosyltransferases, immunoglobulin G, G-quadruplex binders, efflux pump inhibitors and molecular hybrids) to novel approaches in natural product chemistry. Synthetically, we have particular strengths in peptide, nucleotide and heterocyclic chemistry, and in the chemical modification of nanoparticles for targeted drug delivery. We also have a strong interest in marine natural products, to explore the potential of natural products derived from marine symbiosis for drug discovery.
Natural product chemistry is also represented by the development of novel analytical approaches to the standardisation of complex mixtures as in plant extracts, and also the use of informatics in drug discovery.
II. Bioinorganic chemistry
The group has a world-leading reputation for its contributions to the development of clinically-useful iron chelators. Deferiprone, the first orally active iron chelator introduced into man was designed by Professor Bob Hider’s research group. The drug is already used worldwide for the treatment of iron overload, and we are now exploring its potential for the treatment of various forms of neurodegeneration as well as parasitic infections.
III. Bioanalytical chemistry & systems biology
The Chemical Biology group is the home of one of the few international laboratories capable of the synthesis and quantitation of hepcidin, a master regulator of iron metabolism. The hepcidin assay developed in Dr Sukhi Bansal’s laboratory is currently being used in clinical studies carried out with Novartis and Vifor Pharma. We also have expertise in the use of mass spectrometry and both liquid and semi-solid-state NMR for metabolomics with both MS and NMR being employed for biomarker discovery and assessing the impact of both existing drugs and New Chemical Entities on cellular metabolism.
IV. Neurodegenerative diseases
A range of behavioural, biochemical, immunocytochemical and in situ hybridisation techniques are used in the study of neurodegenerative disease. Current interests centre on the role of proteasomal function in cell death in Parkinson’s disease, the use of non-dopaminergic approaches to the treatment of the symptoms of Parkinson’s disease and the development of neuroprotective approaches to the treatment of the illness that will slow or stop disease progression.
V. Pulmonary pharmacology
The Sackler Institute of Pulmonary Pharmacology was established in 1993 to provide multidisciplinary research to investigate the mechanisms and pharmacological basis of respiratory diseases. The Institute also has good collaborative links with clinicians in the School of Medicine and with Department of Respiratory Clinical Pharmacy, University of Rome, Tor Vergata (Prof Mario Cazzola) that allows translational research to be undertaken in patients with respiratory diseases like asthma and chronic obstructive pulmonary disease. A number of models have been developed to further our understanding of the pathogenesis and treatment of lung disease. Research areas include the cell and molecular basis of inflammatory cell recruitment, airway remodelling and airway hyperresponsiveness. The use of cell based assays, in vitro organ bath studies and in vivo models of characteristic features of pulmonary disease allow us to probe the mechanism of a variety of intracellular signalling pathways, receptors, adhesion molecules, inflammatory mediators and cells in these processes. We also have extensive expertise in heparin research and have collaborative projects with National Institute of Biological Standard and Control, Potters Bar (Dr Elaine Gray and Professor Barbara Mulloy).
VI. Vascular biology and inflammation
This research focuses on the biological systems underlying vascular physiology and pathophysiology in inflammatory and related disorders, including sepsis, arthritis and thermoregulatory dysfunction. Ongoing interests include the development of translatable preclinical research models to understand whole body responses to sepsis, trauma and other cardiovascular diseases with a particular focus multi-parameter analysis including hemodynamic and blood flow measurements in the macro and micro circulation.