Professor Keith Jones MA PhD CChem FRSC

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.

Professor Jones is a medicinal chemist involved in designing, synthesising and optimising small molecules as inhibitors of various proteins and signalling pathways.

The aim of this work is to develop these compounds into clinical candidates suitable for early clinical trials as potential new cancer therapeutics. Professor Jones is Leader of the Medicinal Chemistry Team 3 within the Cancer Research UK Cancer Therapeutics Unit. This team is involved in all stages of drug discovery from hit generation through to candidate selection and the key skills are in the synthesis of small molecules and in understanding their interactions with proteins both in vitro and in vivo.

Professor Jones carried out his undergraduate studies in Natural Sciences at Cambridge University and followed this with a PhD in organic chemistry from the same institution. He was appointed to a lectureship at King’s College London where he stayed for 18 years, with the exception of a year carrying out research at Columbia University in New York.  Having been promoted to Reader in Organic Chemistry in 1995, he moved to a chair at Kingston University where he led a multidisciplinary research group in biomedical sciences until moving to his current position at the ICR in 2005. He is currently Deputy Dean (Biomedical Sciences) with responsibility for students and other academic matters.

He is most widely known for his work in the area of heterocyclic synthesis and especially the way in which he and his group developed the use of carbon-centred free radicals in the synthesis of heterocyclic compounds.  He has been involved in a number of collaborative projects with biologists and clinicians that have led to compounds possessing potent activity against the parasite that causes bilharzia, Schistosoma mansoni, and to compounds that inhibit the sodium/potassium pump that controls hypertension. He has a significant current interest in discovering small molecules that interfere with protein/protein interactions and using various approaches to understand the role and behaviour of such compounds.

Professor Jones has held a number of positions within the Royal Society of Chemistry including secretary and chairman of the Heterocyclic and Synthesis Group as well as vice-chair of the Organic Division. He has also been chairman of the Fine Chemicals Group of the Society of Chemical Industry. He has been involved in the organising and running a number of national and international meetings in the general area of organic synthesis and medicinal chemistry. He has been a visiting professor at the University of Barcelona and the Australian National University in Canberra.

In his spare time, Professor Jones coaches youngsters in cricket and football, enjoys opera and wine, and climbs mountains, mainly in the Lake District and Scotland.