Dr Ian Collins PhD FRSC CChem

The discovery and development of new small molecules as anticancer therapeutics.

The core of our research is the design and synthesis of new molecules to inhibit the activity of proteins responsible for the development and progression of cancer. The team is involved in several anticancer drug discovery projects at different points in the drug discovery pathway.  We have particular interests in the discovery and development of small-molecule inhibitors of kinase enzymes, and also in compounds that can inhibit proteins involved in cellular stress responses. Our current targets of interest include PKB/Akt, CHK1, CHK2, IRE1 and HSP70.

We design and synthesise new compound libraries for high-throughput screening, often inspired by biologically active natural products or using information from structural biology studies. We develop new synthetic chemistry to prepare the compounds and have a strong track record in the assembly of functionalised heterocyclic molecules. Many of our current drug discovery targets share a common natural substrate, the nucleotide ATP, and we are involved in the design of new scaffolds for inhibitors based on the binding modes of nucleotide cofactors.

We explore the structure-activity of hits arising from fragment-based or high-throughput screening to select lead series for further development. We collaborate with structural biologists and molecular modellers to use structure-based methods to improve the properties of the compounds. We contribute synthetic and medicinal chemistry expertise to the multi-disciplinary drug discovery projects in the CR-UK Cancer Therapeutics Unit. Through collaborations with in vitro and in vivo biology teams, we optimise the molecules to produce potent compounds with antitumour activity, leading ultimately to the selection of preclinical development candidates.

I am fascinated by how to make new molecules with useful biological activities. My work at the ICR aims to discover and develop new drugs to treat cancer, and I have been involved in drug discovery research for 20 years since starting my career as a medicinal chemist in a major pharmaceutical company. I have a strong interest in using protein structures to understand how drugs bind to their target proteins, and how to improve their properties. My team has transformed several hit compounds to potent and selective potential drug molecules using this approach. One of our projects has recently led to a compound beginning clinical trials, and others are at various stages on the journey to the clinic. We collaborate extensively with our colleagues in the ICR and other organisations to use the compounds we make as tools to understand cancer biology and to develop them as drug candidates. I have a long-standing interest in the synthesis of heterocycles and many of my team’s projects look at new, efficient ways to put together these important molecules.

Before joining The Institute of Cancer Research, I trained as a synthetic chemist under the supervision of Professor Andrew B Holmes at Cambridge University, receiving a PhD for research into a new way of making alkaloid natural products. I joined the Neuroscience Research Centre of Merck Sharp & Dohme Ltd as a drug discovery chemist, researching new drugs to treat psychiatric and neurological disorders. Major contributions included the discovery of the first selective antagonists for the dopamine D4 receptor, the development of sub-type selective GABA-A agonists as anxiolytics, and the discovery of potent gamma-secretase inhibitors for the treatment of Alzheimers disease. In 2003, I moved to my current post in the Cancer Research UK Cancer Therapeutics Unit at the ICR, becoming a Reader in Medicinal Chemistry in 2008.