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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].
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).
Research by Professor Jones, Department of Chemistry, University of Cambridge, resulted in the development of a new method for preparing composite solids, involving the grinding of two or more crystalline solids in the presence of small volumes of liquid. This so called "liquid assisted grinding" (LAG) which produces novel solids with bespoke physical and chemical properties, is now routinely used by the major pharmaceutical companies to screen for new drug forms as part of their drug product development process.
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.
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).
Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes.
The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater efficacy (less catalyst needed and higher yield of labelled product, giving cost savings), greater speed (efficiency savings), and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
Even since 2008, their adoption within the pharmaceutical industry has been extremely rapid; e.g., the multinational pharmaceutical company AstraZeneca now applies the Kerr methodology to 90% of their relevant candidate compounds. Additional impact has been achieved by Strem Chemicals who have been manufacturing and marketing the catalysts worldwide since October 2012. Even in that very short period, multiple sales have been made on three continents providing economic benefit to the company.
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).
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.
ProTide technology, discovered by the McGuigan team at Cardiff University, is a pro-drug strategy with proven capacity to generate new drug candidates for nucleoside-based antiviral and anti- cancer indications. In the assessment period the McGuigan team has attracted more than £2 million direct research funding through sustained collaborations on ProTide technology with global pharmaceutical companies and smaller biotech firms in the USA and Europe. In the same period, either through working directly with Cardiff or by independent adoption of McGuigan's research, eight ProTide entities have progressed to clinical trials as cancer, HIV and hepatitis C treatments. The technology is demonstrating significant commercial impact for companies with ProTide-based drug candidates.
Research by the School of Pharmacy played a key role in the 2008 regulatory approval of Janssen Pharmaceutica's HIV drug Intelence®. As a poorly soluble drug, Intelence® required specialist formulation and was the first formulation of its type to be approved by the FDA and EMA. Intelence® offers significantly improved clinical outcomes due to its efficacy in patients with HIV resistance. Global Intelence® sales in 2012 were $349M, with additional not-for-profit supplies to resource-limited countries. As a result of this landmark regulatory approval formulation development strategies at Janssen were adapted enabling a further poorly soluble drug to reach the market. Telaprevir, a second-generation Hepatitis C treatment (marketed as Incivek®, Incivo® & Telavic®), gained global regulatory approval in 2011. 2012 sales exceeded $1bn in the US alone.