The influence of the 'organizational factor' on compound quality in drug discovery

Key Points Using patents published by leading pharmaceutical companies in the 2000–2010 period, the molecular properties of the compounds acting at the drug targets pursued have been analysed. Over the past decade, there has been little overall change in bulk properties that influence absorption, distribution, metabolism, excretion and toxicity (ADMET) outcomes, such as lipophilicity and size. There are marked differences in molecular properties between organizations, which are maintained when the targets pursued are taken into account. Target-unbiased molecular property differences between companies, attributable to divergent corporate drug design strategies, are comparable to the differences between the major drug target classes. Data from patents with single-compound examples suggest that molecular property attrition begins before the selection of candidate drugs. It is concluded that a substantial sector of the pharmaceutical industry has not modified its drug design practices and is still producing compounds with suboptimal physicochemical profiles. In the past 15 years, it has become clear that physicochemical properties of drug candidates, such as lipophilicity and molecular mass, have an important influence on the likelihood of compound-related attrition during development. By analysing the properties of compounds described in patents from leading pharmaceutical companies between 2000 and 2010, this article indicates that a substantial part of the industry has not modified its drug design practices accordingly and is still producing compounds with suboptimal physicochemical profiles. Physicochemical properties such as lipophilicity and molecular mass are known to have an important influence on the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of small-molecule drug candidates. To assess the use of this knowledge in reducing the likelihood of compound-related attrition, the molecular properties of compounds acting at specific drug targets described in patents from leading pharmaceutical companies during the 2000–2010 period were analysed. Over the past decade, there has been little overall change in properties that influence ADMET outcomes, but there are marked differences in molecular properties between organizations, which are maintained when the targets pursued are taken into account. The target-unbiased molecular property differences, which are attributable to divergent corporate drug design strategies, are compara