Lead optimization in 12 months? True confessions of a chemistry team

In 1998 GlaxoWellcome embarked upon a new enzyme-inhibitor programme. This programme featured an aggressive timeframe of seven years, from the start of medicinal chemistry through to drug launch. This period, dominated as it was by the constraints of the clinical programme, translated into a lead-optimization phase of no more than 12 months. In this article, we describe our attempts to meet this target, examining not only what we did and what worked, but also what didn't work and, most importantly, what we learnt as a result. At a time of considerable upheaval and challenge to the traditional model of drug discovery, we hope our experiences might stimulate interest, empathy and further discussion.