Integrative Molecular Informatics for Drug Safety

Integrative Molecular Informatics for Drug Safety

Author: Jordi Mestres

Anticipating safety concerns much earlier in the drug discovery process is at the top of any today’s wish list from pharmaceutical companies. Not surprisingly, the Innovative Medicines Initiative Joint Undertaking (IMI-JU) funded in 2009 the eTOX project aiming at developing novel computational strategies to better predict the preclicinal toxicity and clinical safety profiles of small molecules.

As part of eTOX, Daniel Muthas and Scott Boyer, AstraZeneca, Mölndal, Sweden, implemented a web application (BioSim) that allows researchers to rapidly detect compounds having similar pharmacological profiles. The service exploits the wealth of pharmacological data accumulated in the company over the years across a panel of more than 85 assays. It also provides an integrated means to link chemistry with both in vitro and in vivo pharmacology.

As data from in vitro pharmacology is generated on an increasing number of safety-relevant targets for large amounts of small molecules, tools exploiting pharmacological similarity – such as the one introduced by Muthas and Boyer – will allow for highlighting potential safety liabilities for molecules that may otherwise escape detection by current approaches based mainly on chemical similarity. Examples of chemically dissimilar compounds having similar in vitro affinity profiles linked to similar in vivo findings are provided.


Because of the relevance of this work in the field of computational toxicology, the article won the Molecular Informatics 2013 Best Paper Award.

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