Research Interests

The team working with Professor Blagg works on the design and synthesis of small molecule therapeutics for the treatment of cancer. Our group has expertise in synthetic and medicinal chemistry, in silico medicinal chemistry, chemoinformatics and analytical chemistry. We work on specific drug discovery projects and on applying new technologies to enable our drug discovery research. Areas of current research interest are highlighted below:

Small molecule inhibitors of mitotic kinases for the treatment of multiple tumour types

Projects are underway to design and synthesise selective, orally bioavailable small molecule inhibitors of mitotic kinases that have an oncogenic role in defined cancer patient populations. This work is in close collaboration with Dr Spiros Linardopoulos (Breakthrough Breast Cancer) and Dr Rob van Montfort in the Section of Structural Biology.

Small molecule inhibitors of the WNT signalling pathway for the treatment of colon and breast cancer

A cell-based phenotypic screening approach has been successfully applied to identify chemical matter that blocks the WNT signalling pathway in a specific manner. Medicinal chemistry driven progression of this chemical matter is underway in collaboration with Merck Serono and Professor Trevor Dale at The University of Cardiff.

In Silico Target Design and Selection

In collaboration with Dr Nathan Brown and Dr Bissan Al-Lazikani we have established, and continue to develop, a suite of in silico tools to enable fast and effective design of small molecule compounds which modulate oncogenic pathways. These in silico tools include virtual screening of large compound libraries and novel scaffold hopping protocols, clustering algorithms and isostere replacement tools.  In addition, we have a major interest in the integration of chemical and biological datasets to educate the selection of appropriate biological targets, biomarkers and drug discovery approaches.

Fragment-based Hit Discovery

In collaboration with Dr Rob van Montfort and Dr Nathan Brown we have established and continue to develop libraries of low molecular weight fragments to enable hit discovery. Subsequent hit follow-up is enabled using high-throughput X-ray crystal structure analyses coupled with biophysical techniques. Projects underway in the Blagg laboratory where fragment-based hit discovery is a particular focus include the discovery of inhibitors of the demethylase family of epigenetic targets in collaboration with the Structural Genomics Consortium in Oxford.