Next Generation Therapeutics
Drug discovery is often the ultimate objective of our research. This aim is facilited by being within the collaborative environment of Cambridge University. Moreover, many pharmaceutical companies collaborate with us to do innovative science
towards next generation therapeutics. This makes our collaborative research group an exciting mix of basic and applied synthetic organic chemistry.
One example of such a project is described below.
The discovery and development of new therapeutic agents has recently moved into a key new area, looking to combine two distinct classes of chemical or biological agents into a single entity. Bringing two different agents together provides
the opportunity for synergistic effects, most notably when one of the components acts as a targeting agent and the other interacting with the desired biological system. One of the leading areas for new synergistic therapeutic modalities is
Antibody Drug Conjugates (ADCs).
Figure General structure of an ADC. ADCs are comprised of three parts: a monoclonal antibody, a cytotoxic agent (the 'warhead') and a structural moiety that joins the two together (the 'linker').
The linker and warhead together are often referred to as the 'payload'.
The antibody of an ADC is selected or engineered to bind to a tumour cell-specific antigen or to an antigen that is overexpressed on the surface of tumour cells. Thus, the antibody guides the ADC selectively
to target tumour cells. Upon binding, the ADC is internalised and the cytotoxic agent is released from the antibody to perform its cell-killing function. ADCs hold considerable promise as anticancer agents, offering the potential of specific
delivery of cytotoxic agents to tumour cells (targeted therapy), thereby avoiding the dose-limiting toxicity of chemotherapy that occurs as a result of its effects on normal cells. Recent years have witnessed tremendous interest in ADCs; two are
already on the market as anticancer agents (Roche's Kadcyla and Seattle Genetics' Adcetris) and there are now over 30 ADCs in clinical trials.
The development of new linkers and warheads by synthetic chemists will be crucial to the further advancement of the field and the emergence of next generation ADCs.
This project is conducted in collaboration with
Ian Paterson and pharmaceutical companies.