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More cost-effective drug discovery using virtual screening

Summary of the impact

The discovery of a new drug can take 10 years, cost in excess of one-billion dollars and involve synthesising and testing thousands of possible drug molecules. Virtual (i.e., computer-based) screening is used in the early stages of drug discovery to focus attention on those molecules in a chemical database that are most likely to exhibit the required drug action and that are hence priority candidates for further, more detailed study. Virtual screening thus increases the cost- effectiveness of pharmaceutical research by bringing novel drugs to patients more quickly.

Work in Sheffield since 1993 on virtual screening has resulted in three computer programs that enable much more effective screening to take place than was previously possible and that are now used throughout the world-wide pharmaceutical industry: GALAHAD (Genetic Algorithm with Linear Assignment for the Hypermolecular Alignment of Datasets), GASP (Genetic Algorithm Superimposition Program) and GOLD (Genetic Optimization for Ligand Docking).

Submitting Institution

University of Sheffield

Unit of Assessment

Communication, Cultural and Media Studies, Library and Information Management 

Summary Impact Type

Technological

Research Subject Area(s)

Mathematical Sciences: Statistics
Information and Computing Sciences: Computation Theory and Mathematics, Information Systems

Managing full scale dynamic performance of civil infrastructure

Summary of the impact

Research in the Department of Civil and Structural Engineering at the University of Sheffield on dynamic performance and vibration serviceability has contributed to internationally applied guidance on building serviceability for floors, buildings, stadia and other structures and has led to the spin-out Full Scale Dynamics Ltd (FSDL). Based on our research FSDL provides applied research and consultancy services, and has delivered projects approaching £1m since 2008. FSDL has demonstrated significant reach through its work with blue chip clients nationally and internationally. Our research has impacted on leading national sport infrastructure (such as Premiership Football stadia and notably the Olympic 2012 Velodrome) and public companies to deliver economic benefits by providing evidence based compliance, demonstrating that stadia, hospitals, manufacturing plants and other public structures comply with safety and vibration serviceability standards. Interventions based on our research and implemented via FSDL have, on numerous occasions, avoided potentially serious economic and safety consequences due to the poor vibration performance of structures.

Submitting Institution

University of Sheffield

Unit of Assessment

Civil and Construction Engineering

Summary Impact Type

Technological

Research Subject Area(s)

Mathematical Sciences: Statistics
Engineering: Civil Engineering

Structure-Guided and Fragment-Based Drug Discovery

Summary of the impact

In 1999, Chris Abell (Chemistry), Tom Blundell (Biochemistry), and Harren Jhoti co-founded Astex Technology Ltd. to develop an X-ray structure-guided, `fragment-based' approach to drug discovery. This led to a significant change in how the pharmaceutical industry approached drug discovery. Astex Technology Ltd developed four molecules in-house using this approach, which have in 2013 reached Phase I/II clinical trials for various tumours. Four further molecules have been taken into Phase I through collaborations between Astex and Janssen, Novartis and Astra Zeneca. In 2011 the company was sold to SuperGen, Inc., for $150 million (ca £100 million), creating Astex Pharmaceuticals, Inc., currently with ~120 employees, and a value of >$500 million (> £320 million).

Submitting Institution

University of Cambridge

Unit of Assessment

Chemistry

Summary Impact Type

Technological

Research Subject Area(s)

Chemical Sciences: Macromolecular and Materials Chemistry, Physical Chemistry (incl. Structural)
Biological Sciences: Biochemistry and Cell Biology

Health and economic impact of a new drug intervention for osteoporosis

Summary of the impact

Research at the University of Sheffield has demonstrated that zoledronic acid is an effective and safe treatment for osteoporosis. It resulted in a new drug intervention (Aclasta/Reclast) which has been licensed in more than 100 countries and shows increased positive outcomes for patients.

As a result of the licensing of the drug, clinical guidelines have changed globally. For patients, the drug provides a preferred method of treatment, evidenced in surveys which show the majority of patients preferred an annual infusion of zoledronic acid to the alternative, which is the standard treatment of weekly oral alendronate.

Industry has invested in research and development of the drug. Novartis has funded studies into the efficacy and safety profile (up to 2012); in 2011, sales of Aclasta/Reclast were US$0.6 billion.

Submitting Institution

University of Sheffield

Unit of Assessment

Clinical Medicine

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences

3) Treatments and diagnostics for Alzheimer's disease

Summary of the impact

Alzheimer's disease (AD) affects one in seven of the population over 60 years of age, and represents an increasing burden on worldwide medical and care resources. Treatments currently available are symptomatic. Despite pharmaceutical industry efforts there has been little indication of a marketable product for long-term treatment.

To address this problem, a joint venture was established in 2001 between the University of Aberdeen and TauRx Pharmaceuticals. A team was created of chemists, biologists, animal behaviourists, working together with a clinical trial team. A drug effective against the progress of AD based on the compound methylene blue was synthesised and scaled up within the Chemistry Department (led by Professor John Storey), with a quality that was proved acceptable through successful phase two clinical trials (2006-8), and is now used in phase three clinical trials which are due to complete in 2015. Several other drug candidates have also been developed and evaluated in pre-clinical and phase one clinical studies that show promise. Collaborations with commercial pharmaceutical companies have as a result led to the manufacture of significant quantities of drug medicines for TauRx Pharmaceuticals based on IP generated within the Chemistry Department and these drugs have been used in clinical trials and for named patient supply (c. 60 patients). This has resulted in increased commercial revenue for these companies and the creation of new employment.

Submitting Institution

University of Aberdeen

Unit of Assessment

Chemistry

Summary Impact Type

Technological

Research Subject Area(s)

Chemical Sciences: Organic Chemistry

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