“The European Lead Factory represents a fantastic opportunity”
DR WILL UNSWORTH
Leverhulme Trust Early Career Research Fellow
For a relatively new research group such as ours, the European Lead Factory represents a fantastic opportunity to see the molecules prepared in our synthetic projects make a genuine impact in medicinal chemistry. Our group is interested in developing novel ring expansion approached to medium-sized ring and macrocyclic peptide mimetics. However, at present we have neither the expertise nor the resources to run bioassays of our synthetic products. By working with the European Lead Factory, >50 of our compounds are now part of the Joint European Compound Library and will soon be part of ELF screening set. The whole process was remarkably straightforward; after submitting our initial proposal and preparing 2 grams of a single synthetic intermediate, all the subsequent chemistry was done in an ELF partner laboratory. It really couldn’t have been any easier from our perspective. To know that our products may one day contribute to addressing some of society's major health problems like cancer or antimicrobial resistance, is extremely satisfying and exciting!
“Go for it and take advantage of the opportunity”
LAURA AITKEN, PHD
In 2018, an 18 trillion-dollar-bill will be paid to treat dementia and Alzheimer’s disease worldwide. It is a condition that will concern us all, either as a patient, as a relative or as one of the few and relatively lucky ones who will only have to pay that bill. About 20 years ago, the Director of Research of my department, Prof Frank Gunn-Moore, discovered a protein, which he suspected was involved in the deterioration of the brain that causes dementia. In order to further investigate the potential for this protein as a drug target, we needed compounds to perturbate its action. My task was to develop an assay suitable for screening. Thanks to the local funding from the Scottish Universities Life Science Alliance (SULSA), I could spend three–four weeks at the European Lead Factory Screening Centre in Newhouse. There, I could work in an industry-like setting to upgrade my assay to the ELF standard. Combining my knowledge of the protein with the ELF expertise and robotics enabled us to optimise the assay really quickly. For a post-doc like me, it was truly a unique experience. I’d recommend to anyone in academia to go for it and take advantage of the opportunity!
"We made incredible breakthroughs"
RICHARD MEAD, PHD
Sheffield Institute for Translational Neuroscience
“Thanks to outcomes of our European Lead Factory programme, Parkinson’s UK decided to allocate 1 million GBP in a unique collaboration resulting in a joint-venture biotech company - Keapstone Therapeutics. The EU Lead Factory compounds inhibit a protein–protein interaction in a very interesting disease-related pathway triggering the internal cellular defence mechanisms against oxidative stress, which plays an important role in neurogenerative diseases like Parkinson’s disease and amyotrophic lateral sclerosis (ALS). It would have been absolutely impossible without the high-quality work that the European Lead Factory provided. From assisting with protein production, the optimisation of the HTS assay, developing a totally new biophysical assay, the hit expansion and medicinal chemistry, new protein constructs, and finally also solving inhibitor-bound protein crystal structures. We made incredible breakthroughs! We see that the European Lead Factory is unique in many aspects. It gives us the opportunity to screen a very good and diverse set of compounds from different sources, including the big pharmaceutical companies’ proprietary collections. Combined with cutting-edge the resources, we have world-class infrastructure at our disposal. With this approach the European Lead Factory plays an important role in filling the gap between basic research and late stage drug discovery. The complex agreement might seem cumbersome, but in the end, it protects the target owner. This is a real plus. I truly recommend the European Lead Factory to all my colleagues.”
"The assay requirements from the EU Lead Factory have become our standard guideline"
MONIKA SCHÜTZ, PHD
Institut für Medizinische Mikrobiologie und Hygiene
“At our lab we are studying gut-derived pathogens. We have identified proteins involved in pathogen virulence that could be targeted in the combat against antibiotic resistance. To further advance our project, we needed chemical tools. This is why we applied to the European Lead Factory, which makes it possible to access a large and high-quality compound collection. The infrastructure, expertise and experience of the EU Lead Factory is impressive. In fact, the list of assay requirements for the EU Lead Factory programmes have become the guideline for screen development by the members of the German Centre for Infection Research (DZIF). If they are fulfilled, we know that the assay and target is suitable for a larger screening campaign. We could not quite attain the threshold for one requirement, but that was resolved by one of my PhD students visiting the European Screening Centre site using their instruments. Furthermore, the University of Oxford group have assisted us producing enough of our target protein to enable a high-throughput screening campaign. In parallel, we’re developing several secondary assays to prove true engagement of the hit compounds with the bacterial target in-house and in collaboration with other EU Lead Factory scientists. Eventually, we hope to use the resulting EU Lead Factory compounds in our mouse model and establish pharmaceutical proof-of-concept in vivo.”
“An exceptionally successful collaboration”
CHRISTOPHER SCHOFIELD, PHD
Head of Organic Chemistry
"We had identified what we believed was a good target, but we did not have the resources to run high-throughput screening. That’s when we became aware of the European Lead Factory. We were pleased to experience that the process of submitting a proposal was easy and straightforward. After a substantial amount of preliminary work, we optimized our assay for 384-well-plate use in collaboration with the EU Lead Factory. Together, we also defined the criteria by which the hit list was composed; I was impressed with the amount of thought that went into these processes. The screen identified chemotypes that we had and hadn’t anticipated, and complementary validation assays were carried out by the EU Lead Factory and in our own laboratories. At present, we are collaboratively optimizing characteristics of promising compounds; we hope to start resistance testing in an in vivo context within a year. Overall, we are extremely satisfied with the progress, from assay optimization to post-hit validation. The EU Lead Factory really offers a collaborative effort rather than a service, with an exemplary level of commitment and professionalism from the EU Lead Factory scientists.”
“An absolutely fantastic initiative”
CHRIS SWAIN, PHD
“High-throughput screening still is one of the main starting points for drug discovery. The EU Lead Factory provides academics and small pharmaceutical companies with access to a state-of-the-art platform for the identification of hit compounds. To have this facility at hand represents a fantastic breakthrough. In addition, the Joint European Compound Library (JECL) compares favourably with what I have seen from other screening collections. As an external advisor to one of the pharma partners, I get to evaluate their screening results to compose a Qualified Hit List of up to 50 compounds. I have noticed that the JECL hit compounds are very ‘drug-like’: they are small with favourable physicochemical properties and limited unwanted functionality. Indeed, I have recommended the EU Lead Factory to academics interested in high-throughput screening against their drug target. Academics might not have the tools to develop a 384-well assay in-house, but it’s worth the effort to seek help elsewhere or to contact the Programme Office for advice: the EU Lead Factory is a unique resource with the potential to provide enormous value to small pharmaceutical companies and universities.”
“A unique opportunity for academic researchers”
MARGIT MAHLAPUU, PHD
Associate Professor in Medicine
“My lab is working on a novel kinase for which no pharmacological tools are available. In our search for an antagonist, we had already performed a small-scale screen that did not identify a compound with sufficient potency to build on. We then turned to the EU Lead Factory, which offered an exceptionally large screen without a fee for service: a unique opportunity for an academic researcher as it is difficult to find dedicated grants for exploitation purposes. The experts from the EU Lead Factory were very proactive, in particular after the initial high-throughput screen. They defined the need within the programme and developed and performed deselection and orthogonal assays which convincingly confirmed target involvement. The hit compounds on the Qualified Hit List have good IC50 values. Together we have continued to work on downstream characterization of the antagonists in terms of selectivity profiling and pharmacodynamics properties in cell systems. I have been highly involved in the programme from the beginning, and the synergy in competencies between my lab and the EU Lead Factory has given the project a big push forward.”
"Experience within the European Lead Factory secured my next job"
Mike Rawling, PhD
Senior Scientist Proximagen Ltd, Cambridge, UK
“My time as part of the European Lead Factory was not only stimulating, challenging and enjoyable, but it was also instrumental in securing me a job as a medicinal chemist in industry. Despite completing a strong and successful PhD in synthetic organic methodology, my appeal to potential employers was minimal due to a lack of complex molecule synthesis and limited medicinal chemistry knowledge. During my postdoctoral position within the European Lead Factory I worked on numerous and diverse complex molecular scaffolds, which employed a wide variety of fundamental chemical reactions. The emphasis on developing molecular libraries with optimal physicochemical properties provided me with an invaluable introduction to modern medicinal chemistry, and the basic principles that all medicinal chemists strive to adhere to when designing molecular targets. I strongly believe that it was my experience within the European Lead Factory and prioritising optimal physicochemical properties that secured me the job over other strong candidates, and I continue to use these principles on a daily basis.”
"My advice to other academics: apply for the EU Lead Factory as soon as possible!"
Freek Janssen, PhD
Leiden Institute of Chemistry, Molecular Physiology,
“At the start of my PhD-project, I screened a commercial library to find hits for our target. The de-selection took a lot of time. In the end, none of the hits from this library could be confirmed at all. My supervisor, Dr Mario van der Stelt, applied for a screening slot at the European Lead Factory, which gave my research a flying start. The expertise in assay development and the access to very high quality drug-like compounds in the screening collection is unique; you can’t find it anywhere else. I learned a lot from the assay development approach. Working with the EU Lead Factory not only accelerated my research, but more importantly it gave other young researchers good starting points as well. In our research group currently three PhD students and several master students are working with the Quality Hit List retrieved from the EU Lead Factory. The EU Lead Factory doesn’t just boost a single drug discovery project; but it can boost the research of several people. My advice to other academics with a high quality assay: apply for the EU Lead Factory as soon as possible!”