Small Molecules

Our expertise in small molecule research spans multiple therapeutic areas, working across disciplinary boundaries and with our NHS partners to bring novel candidates to the market, and breathe new life into existing candidates through repurposing.

UCL has the expertise to bridge the development gap between target identification and robust lead molecules that are suitable to form the foundation of successful drug discovery projects.

UCL SLMS has also invested £1.9M in dedicated institutional support groups and associated equipment (2008-2013), matched with significant external funding from MRC, WT and CRUK (~£3M).

A full list of UCL’s research facilities and equipment can be explored in the UCL Research Equipment Catalogue.

Case study: Professor David Selwood - the Drug Designer

Professor David Selwood is a designer and creator of new drugs, by building compounds specifically to target known structures. This approach has led to the development of VSN16R to treat involuntary muscle contraction in multiple sclerosis.

Professor David Selwood exploits structure-based drug design.

Professor Selwood’s approach to drug design exploits the power of modern computing and advances in structural biology. Starting with the structure of a target, his aim is to design compounds that will bind to an active site, to inhibit activity or to mimic the activity of a natural signalling molecule. In the latter case, the challenge is to design a chemical analogue that retains the required biological properties, is metabolised more slowly than natural biological mediators, and can be synthesised in the lab.

Development of VSN16R followed precisely this route. It is based on a naturally occurring lipid signalling molecule, anandamide, which showed interesting properties in animal models of multiple sclerosis, work carried out in collaboration with Professor David

Baker. VSN16R targets spasticity, an involuntary prolonged muscle contraction commonly experienced by multiple sclerosis patients.

Although some drugs are available to treat spasticity, they do not work for everyone and have severe side-effects, including sedation and cognitive dysfunction, so there is a great need for alternatives.

VSN16R has been designed to act on a receptor not targeted by existing treatments. With promising pilot data, Professor Selwood was able to obtain translational funding from the Wellcome Trust, and later substantial Technology Strategy Board and commercial investment, to support studies at least as far as phase I.

In November 2013, phase I trials of VSN16R began on 72 healthy volunteers. With input from UCLBusiness, he has also established a spinout company, Canbex Ltd, to manage the IP associated with VSN16R. Initially set up as a lean, low-cost vehicle specifically for VSN16R, Canbex is now providing a route for its development and further commercialisation.

Partnership example - Eisai

In 2012, UCL and the Japanese pharmaceutical company Eisai entered into an agreement to establish a major drug discovery and development collaboration.

The pioneering alliance involves researchers from both organisations working together to investigate radical new ways of treating neurological diseases such as Alzheimer’s, Parkinson’s and other related disorders.

While UCL provides unmatched scientific expertise and numerous leads for the development of new therapeutics, Eisai brings the experience and expertise of drug development, including assay development and medicinal chemistry as well as regulatory and clinical expertise, that will be required to bring new products to market.

A powerful partnership

Professor Michael Duchen (left) with Dr Gyorgy Szabadkai

Professor Michael Duchen (left) and Dr Gyorgy Szabadkai are among the first UCL researchers to team up with the Eisai pharmaceutical company, to develop agents targeting a key mitochondrial process.

Having spent more than two decades exploring mitochondrial biology, Professor Michael Duchen believes the time is now ripe to begin using this new knowledge therapeutically. With Dr Gyorgy Szabadkai, he is leading one of the first projects supported through the innovative UCL–Eisai partnership established to develop new therapeutics for neurodegenerative diseases.

Professor Duchen had had contact with Eisai when it occupied laboratories within UCL. Recently, he and Dr Szabadkai had begun to discuss with Dr David Miller in the Translational Research Office about the possibility of launching drug development work. The two strands came together, with Professor Duchen being selected to lead one of the first three projects to be progressed through the new partnership with Eisai.

During the course of his research, Professor Duchen has identified several possible targets for intervention. Through extensive discussions with Eisai, which brought its expertise in target validation in drug development, one of these was chosen as the basis of the new project.

The critical pathway is one that, when activated, triggers a cascade of events that eventually leads to the death of the cell. It has been implicated, to varying degrees, in a range of conditions, including Parkinson’s disease, Alzheimer’s disease and multiple sclerosis, as well as tissue damage caused by oxygen deprivation.

The first stage of the project, says Professor Duchen, is to refine their assay of mitochondrial function. Using existing departmental high-throughput screening equipment, they will then screen an Eisai compound library to identify hits affecting their process of interest. Follow up of these hits will help to identify their specific molecular targets, while their effects in different disease models will guide decisions about potential conditions to be targeted.

Dedicated Institutional Support Groups

  • ChemiBank is based in the Wolfson Institute of Biomedical Research. Comprising ~40,000 compounds, its primary purpose is to facilitate the discovery of tools and lead compounds for protein based targets.
  • The Laboratory for Molecular Cell Biology has established the Translational Research Resource Centre (TRRC) which provides high-content, high throughput, cellular screening with foci on the identification of small molecules as potential therapeutic lead compounds and bridging basic molecular mechanisms to clinical applications.
  • The Translational Research Office (TRO) has established a new Drug Discovery Group, which focusses primarily on medicinal chemistry. Based in the School of Pharmacy, the group provides theoretical and practical support for projects.

Coordinated working amongst these groups: the TRO Drug discovery group (medicinal chemistry), ChemiBank (compound collection and screening) and the LMCB Translational Research Resource Centre (high content phenotypic screening), provides a strong expertise platform to bridge the development gap between target identification and robust lead molecules that are suitable to form the foundation of successful drug discovery projects.

Academic Research Activities

  • The School of Pharmacy merged with UCL in 2012 and brought a broad range of pharmaceutical research activities into the College. Since the merger, significant investment has been made into several drug discovery related posts, in particular, professorial appointments in medicinal chemistry and chemical biology.
  • The Department of Chemistry is involved in several collaborative drug discovery projects with colleagues across the School of Life and Medical Sciences. The core organic chemistry research in the department is a rich source of new chemistries and compounds for exploitation via Chemibank.
  • The Centre for Computational Science engages in computational chemistry and modelling and also takes a lead in The Virtual Physiological Human Network of Excellence. Computational studies also have access to UCL’s Legion supercomputing facility.
  • The Centre of Chemical Biology focusses on the discovery and development of chemical probes to facilitate the elucidation of biological processes.
  • The Institute of Structural and Molecular Biology has strengths in protein crystallography and this is complemented around the College by a range of techniques for exploring protein-ligand interactions that encompasses NMR, MS, ITC, SPR and Thermofluor.
  • The Wohl Virion Centre has the only cell based screening facility in a class 3 safety environment in academia in the UK, thus allowing UCL to pursue drug discovery projects on human pathogens.