The project team have identified a first-in-class small molecule inhibitor of the major cell death regulator protein FLIP which shows efficacy in pre-clinical models of NSCLC. Dr Longley will be presenting a poster detailing the development and preclinical assessment of the compounds at the AACR (American Association for Cancer Research) meeting in Philadelphia on the 19 April (Poster LB-037/18).
NSCLCs, which constitute around 87% of all lung cancers, are relatively insensitive to chemotherapy and so novel drug treatments are crucial. Under the agreement, Domainex has applied its expertise in medicinal chemistry and assay biochemistry to support Queen’s University Belfast’s team of cancer biology experts in its efforts to identify new drugs to treat this serious and life-threatening disease.
Scientists led by Dr Longley at Queen’s University, working in close collaboration with Domainex, discovered drug-like compounds that inhibit the interaction between two proteins, FLIP and FADD. Overexpression of FLIP is a key mechanism that prevents the natural or drug-induced death of several types of cancer cells, including those found in many lung tumours. Therefore, inhibiting the function of FLIP may be a highly effective way of enabling the tumour to be destroyed.
In 2012, this programme received a £4 million research grant from the Wellcome Trust’s Seeding Drug Discovery scheme. Domainex and Queen’s University Belfast jointly identified hit compounds and have now conducted lead optimisation to develop small molecules that show efficacy in pre-clinical models of lung cancer. The team now aims to progress the programme to a clinical candidate.
Eddy Littler, Chief Executive Officer of Domainex, commented: “We are very pleased to be working with the team at Queen’s University Belfast, who have unrivalled expertise in the study of cancer drug resistance. The successful prosecution of this project, alongside two other Wellcome Trust funded collaborations; one with St George’s University of London and the University of Manchester, and another with the Institute of Cancer Research, demonstrates the value of Domainex’s core drug discovery expertise. These three projects, together with other work that we are undertaking, illustrate our strong commitment to the support of academic translational research. The dual combination of the LeadBuilder platform and our medicinal chemistry expertise creates an outstanding drug discovery engine.”
Dr Daniel Longley added: “We are delighted that the research programme is progressing well and showing such great promise for the treatment of lung cancers and other cancers, such as colorectal cancer. We look forward to our Scientists continuing to work closely with Domainex and thank the Wellcome Trust for its belief in our research and its support in this crucial area of disease research, which will ultimately lead to better treatment options for patients and significantly improved clinical outcomes”.
Cancer Research at Queen’s University Belfast
The Centre for Cancer Research and Cell Biology (CCRCB) was developed with the explicit aim of translating basic scientific programmes into the clinical arena and is a dynamic research Centre within the School of Medicine, Dentistry and Biomedical Sciences in Queen’s University Belfast. Adjacent to the Northern Ireland Clinical Cancer Centre on the Belfast City Hospital campus, CCRCB is the first Comprehensive Cancer Centre in Ireland and is one of 15 Cancer Research UK (CRUK) designated Centres of Excellence in the UK. The Centre was also awarded Experimental Cancer Medicine Centre (ECMC) status, one of 18 such UK Centres.
For further information on our research programmes, please visit the CCRCB website: www.qub.ac.uk/ccrcb/.
Domainex is a drug discovery company that provides services; including computational and medicinal chemistry, gene cloning and expression, to pharmaceutical and biotechnology companies and to academic research groups. It also offers a unique proprietary technology known as Combinatorial Domain Hunting which is a patented method for expressing difficult protein targets. LeadBuilder is the proprietary lead generation platform that has been developed by Domainex to provide unusually rapid and cost-effective access to high-quality hits. As such, it is particularly well-suited to the needs of groups engaged in translational research, and emerging biotechnology and pharmaceutical companies. Domainex is also developing its own pipeline of pre-clinical drug candidates.
Domainex is based on the Cambridge Science Park, England.
For more information see: www.domainex.co.uk
About the Wellcome Trust
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.Domainex and Queens University Belfast Collaborate to Develop new Lung Cancer Drug