Professor Julian Blagg MA DPhil CChem MRSC

The design and synthesis of small molecule therapeutics for the treatment of cancer

Tremendous progress has been made in our fundamental understanding of cellular processes that lead to the initiation and progression of tumours. For these exciting breakthroughs to translate into patient benefit requires the discovery of therapeutics that selectively modulate these aberrant cellular processes. Many of these therapeutics are, and will continue to be, small molecules designed and synthesised by medicinal chemistry teams such as ours.

Our research is focused on the design and synthesis of safe and effective small molecule therapeutics for the treatment of cancer by targeting specific proteins and pathways implicated in the disease. Our work is conducted in close collaboration with clinical, genetics, biology, structural biology and drug metabolism experts. Our team works at all stages of a drug discovery project: from early target identification and hit discovery, the delivery of chemical tools to build our understanding of the underlying biology and ultimately to the selection of preclinical development candidates.

Hit discovery is achieved through fragment screening, high-throughput screening of in-house and external compound collections, virtual screening and rational design. Lead optimisation of these hits exploits the synthetic, medicinal and computational chemistry skills within the team. Team members work in multidisciplinary projects and have an excellent opportunity to build expertise in a wide range of medicinal, synthetic, analytical and computational chemistry skills.

Current projects include the optimisation of inhibitors of mitotic kinases using structure-based design and the discovery of small molecule inhibitors of the WNT pathway in collaboration with Merck Serono.  We are also applying fragment-based hit discovery to selected epigenetic targets in collaboration with the Structural Genomics Consortium. In addition, in silico medicinal chemists in the team are developing novel scaffold hopping and multiparameter optimisation protocols for broad application in drug discovery research.

The work of Professor Julian Blagg and his team is focused on the discovery of small molecule therapeutics for the treatment of cancer. This work is conducted in close collaboration with clinical, genetics, biology, structural biology and drug metabolism experts at the ICR and externally.

Professor Blagg studied chemistry at the University of Oxford where he completed his DPhil in 1986—working with Professor Steve Davies on organometallics in organic synthesis. After a two-year Royal Society Fellowship in Geneva working with Professor Wolfgang Oppolzer on asymmetric organic synthesis, he joined Pfizer in 1988 as a medicinal chemistry team leader. He pursued his interest in drug discovery research at Pfizer, in the US and the UK, for 19 years. His work led to the discovery of multiple clinical development candidates across the therapy areas of urology, cardiovascular, inflammation, tissue repair, sexual health and metabolic disease. As well as medicinal chemistry design, he also developed expertise in compound features and physicochemical properties linked to toxicity, and small molecule pharmacokinetics.

Professor Blagg joined the Institute of Cancer Research in 2007 to pursue his research interests in all aspects of medicinal chemistry towards the discovery of safe and effective treatments for cancer patients. He is Head of Chemistry and Deputy Director of the Cancer Research UK Cancer Therapeutics Unit and Deputy Head of the Division of Cancer Therapeutics at the Institute of Cancer Research. He is a Vice President of the Organic Division of The Royal Society of Chemistry, and serves on scientific advisory boards for several non-for-profit and commercial drug discovery groups.