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Research by the School of Pharmacy has underpinned the development of fluorescent ligand probes that have opened-up new pathways in drug discovery. These ligands have been commercialised through the formation of the spin-out company CellAura Technologies Ltd, and have been made globally available through a number of distributer agreements. Customers include pharmaceutical companies (e.g. Pfizer, AstraZeneca), drug discovery biotechs (e.g. Addex, Heptares) and drug discovery technology providers (e.g. CisBio). These ligands provide alternatives to the use of radio-ligands, giving more informative and safer solutions for industrial drug discovery. This has, for example, enabled: a new direction in G protein-coupled receptor research at Novartis Pharmaceuticals UK Ltd; validation of Promega Corporation's new drug-binding assay; and superior performance in the establishment of cell lines at inSCREENex GmbH.
Fluorescent ligand technologies developed by Professor Hill and Dr Briddon in the Pharmacology research group, in collaboration with Professor Kellam in the School of Pharmacy, permitted biophysical analysis of G-protein coupled receptors (GPCRs) at the individual cell and molecule level for the first time. The technologies have been commercialised through the spin-out business, CellAura Technologies (and their distributors Abcam, Sigma-Aldrich and others), generating revenues and making the products available to researchers and drug discovery communities worldwide. Custom product developments with global pharmaceutical companies and drug screening reagent providers have generated further partnership revenues and technology benefits. Nottingham-trained researchers are now employed worldwide, broadening the technology's impacts.
Research conducted at the University of Bristol since the late 1990s has pioneered the development of over 60 chemical probes that are selective for individual ionotropic and metabotropic glutamate receptors. The development of these probes has led to numerous commercial impacts, including: the establishment of two companies, which both sold during the assessment period for a combined value of £85 million, and sales revenue for global providers of biochemicals. This research has also stimulated considerable industry investment in drug development.
Original basic research on melatonin receptors undertaken at the Rowett Institute, University of Aberdeen, and funded by the Scottish Government, provided the opportunity for Servier pharmaceuticals to develop a new line of therapeutics for depression.
The company exploited Rowett know-how and invested in new research to develop a new line of compounds and to understand their structure-function relationships. This work enabled the development of melatonin analogues for clinical trials and ultimately led to the development of melatonin compounds for treatment of circadian related disorders.
One (S20098) was identified as having positive effects for disrupted circadian rhythms and beneficial outcomes for patients with depression. S20098 (also known as Agomelatine) was launched after EU authorization in 2009 as a novel anti-depressant drug called Valdoxan®. Today Valdoxan is an award winning anti-depressant drug recognised for its novel mechanism of action and few side effects. Valdoxan is the only anti-depressant drug to be brought to the market in the last 10 years. In summary, supported by investment from industry research undertaken at the University of Aberdeen contributed to the development of a novel antidepressant drug that provides a new clinical intervention with advantages over previously available antidepressants that will make a significant impact on the health and well-being of those afflicted by depression.
Research by Professor Kevin Fone in the Neuroscience group has established and characterised rodent models of CNS disorders that have been instrumental in validating several 5-hydroxytryptamine (5-HT) receptors as therapeutic drug targets to treat learning and memory dysfunction in humans. Specifically, animal studies to validate the 5-HT6 receptor for cognitive impairment in Alzheimer's disease (AD), depression and schizophrenia have resulted in R&D investment in drug discovery programmes by several global pharmaceutical companies. Consequent advances in healthcare benefits (current and potential) are also summarised.
Professor Geoffrey Burnstock and colleagues' establishment of the molecular structure of the P2Y class of receptor led to the cloning of several receptors within this class, which are increasingly seen as therapeutic targets for a variety of disorders. Indeed, drugs acting at these receptors are already improving patient health worldwide by reducing the risk of thrombotic events in people suffering from myocardial infarction or ischaemic stroke (via P2Y12 receptor antagonists) and by relieving the symptoms of dry eye disorder (via P2Y2 receptor agonists). Burnstock and colleagues also cloned the P2X3 receptor which mediates pain information, and P2X3 antagonists are being developed as novel analgesics. As well as clear clinical benefits, these drug developments are associated with substantial economic and commercial benefits.
Research led by Dr. Peter Richardson in the Department of Pharmacology led to the development of an A2A adenosine receptor antagonist (istradefylline) for the treatment of Parkinson's disease. In 2001, Dr Richardson founded the spin-out company Cambridge Biotechnology (CBT) to develop these drugs. A pH-sensitive adenosine A2A receptor agonist is now being developed for the treatment of neuropathic pain, with one product licensed for use in Japan in 2013 (Nouriast). Small-molecule leptin mimetics as potential anti-obesity drugs were also developed, initially by CBT and since 2009 by Astra Zeneca following acquisition of the research programme. CBT has undergone a number of high-value acquisitions, by Biovitrium, Proximagen, and most recently Upsher-Smith. It continues to operate as a wholly-owned subsidiary, employing 30-35 people from 2001 to the present.
Kinases, the enzymes that catalyse phosphorylation events, have been implicated in hundreds of different diseases, and hold rich promise for drug development. In 1998, The University of Dundee developed the first systematic assay to analyse the selectivity of protein kinase inhibitors, termed `kinase profiling'. This technology has been crucial for the development of new therapeutic drugs targeting protein kinases. In order to promote drug discovery in the area of kinases, the Division of Signal Transduction Therapy (DSTT) was formed and provides a unique collaboration between the University and six of the world's leading pharmaceutical companies.
The Guide to Receptors and Channels has contributed to the development and maintenance of the intellectual infrastructure of pharmacology. The key tools it provides have influenced appropriate identification of lead drug targets and how best to study them and, as a result, it has received endorsement and financial support from the Pharmaceutical Industry. It is used widely as a teaching aid for undergraduates and research postgraduates and provides the general public with accurate information on prescription drug action. It led to the formation of the Guide to Pharmacology website in collaboration with the International Union of Basic and Clinical Pharmacology.
Serum amyloid P, or pentraxin-2, is a pentameric calcium-binding protein that binds to amyloid fibrils. It has been implicated in the protection of those fibrils from proteolytic digestion and in the immune response to tissue damage. The structure of pentraxin-2 was first solved by Steve Wood and his co-workers in Tom Blundell's lab at Birkbeck in the 1990s. Wood has continued his work on the pentraxins at UCL, and the company Pentraxin Therapeutics Ltd was spun out of UCL to design and develop pentraxin-binding ligands (based on its structure) as potential treatments for Alzheimer's disease and amyloidosis. Promedior Inc. in the US is developing recombinant forms of pentraxin to control fibrosis. Several of these molecules are now in clinical trials.