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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).
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.
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.
Combinatorial Domain Hunting (CDH) technology is a technique for producing fragments of proteins that are soluble and tractable for biophysical analysis. It was developed between 1999 and 2008 at Birkbeck College, in the laboratory of Dr Renos Savva. This technology was patented in 2001 and the biotech company Domainex Ltd was then formed to commercialise it. In 2007, Domainex merged with a UCL spinout company, NCE Discovery Ltd. The company has attracted over £3m in investment and employs about 31 people. In addition to its contract research programme, it has developed an in-house drug discovery programme utilising CDH. Early in 2012 a patent was filed on a series of inhibitors of the protein kinases IKK03b5 and TBK1, which are validated drug targets for cancer and inflammation, and the first of these are expected to begin clinical trials in 2014.
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.
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 computer technology has been invented to accelerate drug discovery. It predicts locations in disease-associated biomolecules where drug molecules could bind, induce shape changes, and thereby bring the activity of the biomolecule under control. A U.S. drug discovery company, Serometrix, has exclusively licensed this technology and incorporated it within their core discovery process. The impact upon them has been:
The Institute of Cancer Research (ICR) founded the spin out company Domainex in 2002 in collaboration with UCL and Birkbeck. The company was set up on the basis of novel research into the expression of soluble protein domains to provide services to a range of bioscience-based companies. Within the period 2008-2013, Domainex has established profitability and positioned itself as a successful company employing over 30 scientists at its laboratories in Cambridge. It has established programmes and contracts with over 20 international clients in medicinal chemistry, drug discovery, monoclonal antibody development and agrochemical science, making a major commercial impact in all these fields.
The activities of the Organic Materials Innovation Centre (OMIC) at the University of Manchester generate impact from its research activities through knowledge transfer to industry. This is exemplified by:
Provision of research-based training in the field of printed electronics and sensors to over 250 people from 2008 onwards.
Nearly all solid dosage forms contain drugs in crystalline form; and all crystals have the potential to `morph', suddenly, into different forms which can affect the safety and efficacy of the medicinal product. A number of high-profile cases in which marketed medicines had to be withdrawn [Lee, et al., Annu. Rev. Chem. Biomol. Eng. 2011, 2, 259-280] led multinational drug company Pfizer to conclude that a greater understanding of polymorphism was required to enable drug product design for the 21st Century. The University of Greenwich pioneered methods to predict crystal behaviour on the shelf and during manufacture that were affordable, timely and effective. It enabled Pfizer to select the optimal polymorphic drug form and manage risk associated with uncontrolled solid-state transformations, thereby safeguarding patients and avoiding huge costs.