The last 5–10 years have seen a dramatic change in the development of new anti-cancer drugs. There has been a move away from cytotoxic agents which acted by damaging the DNA of all cells. These agents—still widely used in a clinical setting—rely on the fact that cancer cells replicate much more rapidly than normal cells and so are more susceptible to such toxic agents. Unfortunately, these drugs lead to wide ranging and debilitating side-effects.
We now understand in much more detail the biochemical pathways that drive particular cancers we aim to specifically inhibit these aberant pathways. The aim is to produce anti-cancer drugs which kill cancer cells in a highly selective manner and are much more like other drugs in their side effect profile and can be taken orally.
Medicinal Chemistry 3 is one of thirteen Teams that together form the Cancer Research UK Cancer Therapeutics Unit, a part of the Division of Cancer Therapeutics.
Within medicinal chemistry, we use all the techniques of modern synthetic organic chemistry to identify and then develop small molecules that target particular proteins in various cellular pathways. This often starts with the invention and synthesis of chemical probes to study the pharmacological effects of inhibition of the target protein.
We subsequently carry out the complex and multifactorial task of optimising our compounds to turn them into potential anti-cancer drugs. This involves ensuring the compounds have sufficient selectivity versus the other proteins in cells, ensuring they are not rapidly metabolised in vivo and that they possess the right mix of physical and chemical properties to be effective in vivo.
The multidisciplinary nature of drug discovery makes it a challenging and rewarding arena to work in, as in addition to specialist chemistry knowledge and skills we have to possess an understanding of the biology involved. The strong and effective interaction between chemistry and biology within the Unit puts us at the forefront of academic drug discovery.
In addition to the directed drug discovery projects, we are involved in more fundamental aspects of research usually involving PhD students. Our particular interests are the synthesis of biologically-active compounds related to natural products, the synthesis of novel kinase inhibitors and the development of small molecules that mimic protein/protein interactions.