It has become increasingly clear that rather than being a single disease, cancer is a heterogeneous collection of diseases. In order to diagnose and treat cancer effectively, strategies for patient selection must be combined with the development of molecularly targeted therapeutics so that patients can receive the drug or combination of drugs which is most appropriate for the treatment of their disease, at the appropriate time. This approach necessitates the involvement of multi-disciplinary teams of basic researchers and clinicians, working within an infrastructure which allows for effective knowledge transfer.
Professor Tim Harrison, Lead Investigator
The drug discovery group at the Centre for Cancer Research and Cell Biology (CCRCB) integrates both academic and industrial scientists as part of a strategic collaboration between Queen’s University, Belfast and Almac Discovery, to facilitate the translation of basic research discoveries into products which can ultimately derive value for patients. Working in close partnership with researchers from across the University and local hospitals, as well as with external researchers, the mission of the Drug Discovery group is to identify molecular targets which are relevant to disease and to develop strategies to modulate their function. Working closely with colleagues within the Centre (which includes the Northern Ireland Molecular Pathology Laboratory and Northern Ireland Biobank), a strong emphasis will be placed on the early development of biomarkers, both to aid patient selection, and to establish that the drug is interacting with its intended target in patients.
Key to the progression of any drug discovery programme is the identification of a chemical compound (either small molecule or peptide/protein based) which can interact with the target. This drug “hit” is then optimised to provide a compound (often termed a Preclinical Candidate) which has the potency, specificity and pharmaceutical properties to interact with the target in humans at a therapeutic concentration which does not cause unacceptable side effects. This candidate molecule is further evaluated in pre-clinical development studies before progressing into clinical trials.
The capabilities of the drug discovery group include:
- Medicinal chemistry expertise in hit identification, hit to lead and lead optimisation;
- Biology expertise in target validation and assay development using multiple formats;
- Fragment screening (using a range of orthogonal biophysical techniques);
- Computer aided drug design and chemoinformatics;
- Bioinformatic expertise in data mining;
- Measurement and interpretation of Absorption, Distribution, Metabolism and Excretion (ADME) and physicochemical properties of molecules;
- State of the art compound storage and data management facilities;
- Pre-clinical and clinical project management;
- International network of collaborators and outsourced service providers.
Research is currently focussed on the discovery of inhibitors of proteases with a specific focus on deubiquitinase enzymes and other ligases involved in the ubiquitin-proteasome system. There is also a strong interest in developing new strategies for the disruption of protein-protein interactions, focussed on the anti-apoptotic protein cFLIP and its role in therapeutic resistance. A third area of interest, which takes advantage of our expertise in peptide and protein engineering, is in the development of novel protein-based delivery vehicles for the specific targeting of therapeutic agents to tumours. Based on these drug discovery capabilities, it is anticipated that molecules will emerge that may be developable into the next generation of clinical medicines. The multidisciplinary environment within the Centre for Cancer Research and Cell Biology, itself situated within easy reach of other QUB research faculties and Clinical Centres, offers an exciting opportunity for chemists, biologists, bioinformaticians, physicists, radiographers and clinicians to combine their expertise to facilitate the drug discovery process.
Dr Rich Williams, Academic Medicinal Chemist
Our lab is an academic medicinal chemistry group focused on the development of small molecule protease inhibitors that are relevant in human diseases, such as cancer and Cystic Fibrosis. Through interaction with Professor Harrison and the Almac Discovery group we have been able to drive the identification and development of a significant number of molecular starting points for exploration. Examples of our current research programes are below:
- Development of small molecule protease inhibitors relevant to human diseases;
- Legumain inhibitor program;
- Cathepsin S inhibitor program (Cystic Fibrosis);
- Cathepsin S in cancer.
For further details of these programs please click here.