The significant failure rate of compounds entering clinical trials, due in large part to safety and efficacy concerns, has led the pharmaceutical industry to invest heavily in new technologies and to integrate safety assessment into the discovery and development pipeline as early as possible.
Computational chemistry and gene-expression analysis have been widely adopted for safety assessment in recent years, and as the fields of proteomics and metabolomics mature, they too are being investigated with a view to combining the different technologies to give a more holistic understanding of the effects of compounds on biological systems.
The integration and analysis of this data presents a significant bioinformatics challenge. To address this need, GeneGo created MetaDrug™, a systems pharmacology and toxicology data-analysis platform.
MetaDrug incorporates chemical structural analysis, metabolite prediction, and ADMET quantitative structure activity relationship (QSAR) models with a database of molecular interactions, gene function, disease and toxicity ontologies and networks, as well as pathway- and network-analysis software. The user can upload, combine, analyze, and visualize multiple data types (genomic, proteomic, and metabolomic) individually or in concert to reveal on- and off-target pharmacological effects, mechanisms of toxicity, and biomarkers of safety and efficacy.
MetaDrug includes a comprehensive chemical and pharmacological database that comprises chemical structures of over 680,000 drugs, metabolites, and xenobiotics along with data on their biological effects from over 1,000,000 in vitro pharmacological-binding assays, 1,500,000 in vitro functional assays, and 600,000 in vivo functional assays.
Additional data covers a wide range of ADMET and physicochemical properties. This resource, coupled with chemical structure similarity and substructure searching; QSAR modeling, including the ability for the user to derive and incorporate custom QSAR models from their own data; and an extensive knowledge-base of drugs and their targets, facilitates comparison of discovery and development compounds to competitors on the market and in clinical trials.
MetaDrug further couples this pharmacological data to GeneGo’s network- and pathway-analysis tools. This provides the ability to query potential biological and toxicological concerns based on chemical structure, which enables triage and prioritization of compounds early in the discovery process.
As compounds progress and empirical data is generated, the data can be visualized on networks and pathways identified through structural analysis. Data-driven analysis can be performed independently or in concert with the structural data, the predicted activities investigated further, and conclusions refined.
Identifying Compound Liabilities