Standing on the shoulders of giants: a retrospective analysis of kinase drug discovery at AstraZeneca.
Sir James Black famously said: 'The most fruitful basis of the discovery of a new drug is to start with an old drug', and this idea has featured in a significant number of kinase drug discovery programmes at AstraZeneca over the past two decades. Of the marketed kinase inhibitors and various clinically trialled agents, candidate drugs and multiple lead optimisation programmes delivered over this timeframe at AstraZeneca the overwhelming majority trace their origins back to a small handful of pioneering drug discovery programmes. Importantly, these projects not only laid the foundations of the organisational expertise on how to 'drug' this important target family but also provided a legacy of internal chemical equity that has had a profound influence on the many kinase-focused discovery efforts that have followed. For agents in late-stage clinical trials today, seemingly the product of rapid discovery phases, the reality is that these are often the products of decades of research. Crucial to the success of these projects has been the medicinal chemists involved, whose intimate knowledge and expertise around key kinase chemical scaffolds has enabled successful medicinal chemistry strategies to be rapidly identified and executed.
AstraZeneca, Oncology iMED, Mereside, Alderley Park, Stockport SK10 4TG, UK. Electronic address: jason.kettle@astrazeneca.com.
Jason G
JG
Kettle
AstraZeneca, Oncology iMED, Hodgkin Building, Chesterford Research Campus, Little Chesterford, Saffron Walden, Cambridgeshire CB10 1XL, UK. Electronic address: david.m.wilson@astrazeneca.com.
David M
DM
Wilson
D000818:Animals; D000970:Antineoplastic Agents; D055808:Drug Discovery; D004345:Drug Industry; D006801:Humans; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011804:Quinolines
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011804:Quinolines