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Herbicides are essential to efficient agriculture to boost crop yield and maintain food supplies in the face of growing demand. However, their use is threatened by a rapid rise in herbicide resistance, a problem that is exacerbated by the limited range of compounds currently in use. In particular, resistance to glyphosate, the compound that currently dominates the market with sales in excess of $4 billion per annum, has emerged far more rapidly than had been predicted. For over twenty years the Sheffield group has worked in collaboration with Syngenta (a world leading agrochemical business) on the development of a novel herbicide targeting IGPD, an enzyme of histidine biosynthesis, to provide an alternative to glyphosate. Over that time Syngenta invested approximately $20M in synthesis and testing of custom chemicals, including conducting worldwide field trials on the lead compound. The Sheffield group determined the structure of IGPD with representative inhibitors which has guided programmes of lead optimisation and greatly informed company decisions on the scope for commercial development. The impact relates to commerce, production and employment, and has significant reach given the vital importance of herbicide development to programmes of sustainable agriculture on a global scale.
Since 2008, pioneering contributions to the field of computational chemistry for drug discovery have been made by InhibOx Ltd., a spin-out company based on the research of Graham Richards and co-workers at the University of Oxford. InhibOx launched Scopius, the world's largest searchable virtual database of small-molecules (>112 million compounds) and pioneered the use of cloud computing for large-scale molecular modelling. The key impact for customers of InhibOx has been the reduced costs in identifying molecular leads for new drugs. InhibOx's work has helped to open up early stages of drug development to smaller companies; 75% of InhibOx's clients are SMEs. Since 2008, InhibOx has received £ 2.8M in income and investment.
The Abraham solvation parameter approach developed at UCL has become integral to the work carried out by drug discovery teams at [text removed for publication] and other major pharmaceutical companies, as well as research and development groups at international chemical companies including Syngenta and [text removed for publication]. It enables chemists to predict physicochemical and biochemical properties of chemicals, including drugs and agrochemicals, rapidly and efficiently, without the need to conduct time-consuming experiments. The method helps drug discovery teams to identify and optimise the most promising compounds, and often results in fewer compounds being made before a candidate is selected, saving time and resources. The approach has been integrated into software used for drug discovery [text removed for publication].
A critical step in drug discovery is accurate determination of bioactive 3-dimensional structures of biologically-relevant molecules. Almond and Blundell's proprietary method for analysing Nuclear Magnetic Resonance (NMR) data has led to a world-first capability and establishment of the company Conformetrix (renamed C4X Discovery in 2013). The platform technology ('MolGyrate') is used to determine the dynamic 3-dimensional-conformation of biologically relevant molecules directly from NMR data within weeks, compared with months to years for traditional methods. C4X Discovery has secured substantial private investment (the company has not disclosed the amount). In 2012 AstraZeneca began to apply the technology across their entire pre-clinical therapeutic pipeline to enhance lead discovery and hit identification.
Genetic tests introduced by insurance companies for dental healthcare in the USA are underpinned by leading research on the interleukin-1 cytokine system carried out at the University of Sheffield. Research in Sheffield has led directly to the development of these tests and has had [text removed for publication]. Implementation of the PSTf0d2 test by Delta Dental (largest dental insurer in the USA) stratifies patients at risk of periodontitis, has informed USA government policy on the use of genetic data in healthcare and has led directly to new dental policies for adults based on personalised IL-1 genetic data. The health value of this is $4.8 billion/year in the USA.
In 1999, Tom Blundell (Biochemistry), Chris Abell (Chemistry) and Harren Jhoti cofounded 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 AZ. In 2011 the company was sold to Supergen for $150 million (ca £100 million), creating Astex Pharmaceuticals, Inc., currently with ~120 employees, and a value of >$500 million (>£320 million).