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Prof Mark Searcey
For many years, most of the drugs used in the treatment of cancer were derived from natural products. These ranged from compounds isolated from the periwinkle plant, such as vincristine, through to compounds from the bark of trees, such as paclitaxel. New natural products fell out of favour because they are generally cytotoxic – they kill all cells that are dividing in the body, not just cancer cells – so they tend to have extremely unpleasant and sometimes life-threatening side effects. Now, these compounds are seeing a renaissance and new natural products are being investigated as they form the basis of targeted drugs – drugs such as antibody drug conjugates or ADCs – that bind selectively to cancer cells and have fewer side effects.
In our laboratory, we have developed methodologies to make natural products known as the duocarmycins. These are extremely potent anticancer agents. Our chemistry means that we can make them efficiently and use a technique called solid phase synthesis to attach them to peptides, to other small molecules, to proteins and to antibodies in order to target them to tumours. We are currently investigating the synthesis of various analogues of these natural products, including inventing new “non-natural” versions, and we can then explore their potential in the treatment of cancer.
Publications
Borylation via iridium catalysed C–H activation: a new concise route to duocarmycin derivatives
Cominetti, M. M. D., Goddard, Z. R., Hood, B. R., Beekman, A. M., O'Connell, M. A. & Searcey, M. 2024, In: Organic & Biomolecular Chemistry. 22, 27, p. 5603-5607
Cartwright, O. C., Beekman, A. M., Cominetti, M. M. D., Russell, D. A. & Searcey, M., 2020, In: Bioconjugate Chemistry. 31, 7, p. 1745–1749
A small molecule drug conjugate (SMDC) of DUPA and a duocarmycin built on the solid phase
Beekman, A., Cominetti, M., Cartwright, O., Boger, D. L. & Searcey, M., 2019, In: MedChemComm. 10, 12, p. 2170-2174