Chemical Biology: What is Its Role in Drug Discovery?

Abstract

For better or worse, there are considerable changes underway in the world of drug discovery. Whilst it is unclear what the future will bring, one possibility is a strategic shift in the modus operandi of the large pharmaceutical companies. One consequence of a shift away from high level investment in “in-house” research and development by pharma could be increased industrial interest in early stage research carried out in biotech, government or charity-funded research centres and academia. In many of these institutions, this type of research is often referred to as “chemical biology”. But what is chemical biology? In this chapter we take a less-trodden path to addressing this question with the overall aim of shedding some light on areas of chemical biology which are relevant to drug discovery. Chemical biology is a difficult topic to define in a few sentences since the subject is very wide ranging. Recent attempts have included an excellent review article in ChemBioChem written by some of the experts in the field (Altmann et al., 2009). A book focusing on the new frontiers in chemical biology has also recently been published (Bunnage, 2010). Interestingly, the Editorial in this book identifies “..reducing the high levels of attrition currently seen in “proof-of concept” Phase II clinical trials” as a key future challenge in drug discovery. It goes on to argue that this can only be achieved through “a much deeper knowledge of biological systems in order to identify and validate those biomolecular targets for which there is the highest possible confidence of disease-relevance in humans”. The Editor concludes by proposing that chemical biology has great potential to help address the challenges that have been summarised above. So again we ask what is chemical biology? Several excellent articles cover this issue in the New Frontiers book (Bunnage, 2010), but here we use an alternative method of probing what chemical biology really involves at the grass roots level. Our goal was to reflect on whether chemical biology, as currently practiced, really is and will be of interest to the drug discovery community in the future. Our chosen approach was to provide a review of all the chemical biology papers which were published in 2009 in the RSC journal Organic and Biomolecular Chemistry. Due to the number of papers, over 300, coverage of many of these exciting pieces of research is brief. We apologise for this and for any we may have inadvertently overlooked. However, our goal was to bring this body of work together in an organised and accessible form and to try and continue efforts to define what chemical biology involves. The chapter is split into three