Understanding Compound Quality
Dr Paul Leeson, Paul Leeson Consulting Ltd, gave this presentation at the “Guiding Optimal Compound Design and Development Symposium” held in Cambridge, MA, USA on 19 March 2015.
A significant body of data suggests that controlling the molecular properties of hits, leads and drug candidates in the drug discovery phase should help to reduce risks of poor drug metabolism and toxicity. Concern for the health of pharmaceutical pipelines stems from analyses of small molecules patented by the industry, which are on average more lipophilic and larger than approved oral drugs. This is relevant too because only ~4% of candidate drugs reach the market and it has been acknowledged that compound-related risks, in dose, exposure and toxicity, can be carried from discovery into more costly clinical development.
Compound quality is controllable, being fixed at the point of design and varies substantially across organizations. Improving compound quality can be facilitated, inter alia, by selection of lead-like chemical starting points, use of predictive chemistry tools and application ligand efficiency measures to guide optimization.
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