Abstract
Both metabolism and transport are key elements defining the bioavailability and biological activity of molecules, i.e. their adverse and therapeutic effects. Structured and high quality experimental data stored in a suitable container, such as a relational database, facilitates easy computational processing and thus allows for high quality information/knowledge to be efficiently inferred by computational analyses. Our aim was to create a freely accessible database that would provide easy access to data describing interactions between proteins involved in transport and xenobiotic metabolism and their small molecule substrates and modulators. We present Metrabase, an integrated cheminformatics and bioinformatics resource containing curated data related to human transport and metabolism of chemical compounds. Its primary content includes over 11,500 interaction records involving nearly 3,500 small molecule substrates and modulators of transport proteins and, currently to a much smaller extent, cytochrome P450 enzymes. Data was manually extracted from the published literature and supplemented with data integrated from other available resources. Metrabase version 1.0 is freely available under a CC BY-SA 4.0 license at http://www-metrabase.ch.cam.ac.uk.Graphical Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-015-0083-5) contains supplementary material, which is available to authorized users.
Highlights
Absorption, distribution, metabolism and excretion (ADME) properties of small molecules are vitally important for their function and potential toxicity, understanding their interaction with transport proteins as well as metabolizing enzymes is fundamental to the discovery and development of e.g. safe, efficacious medicines and skin products
Numerous valuable publicly available transporter-related data sources exist that are either specific to membrane transporters (e.g. TP-search [1], UCSF-Food and Drug Administration (FDA) TransPortal [2], TSdb [3], Human Transporter Database [4], HMTD [5], TCDB [6], solute carrier (SLC) Tables [7] and Membrane Proteins of Known 3D Structure [8]) or contain transporter data as part of a broader collection of biological and pharmacological data (e.g. ChEMBL [9], HMDB [10], DrugBank [11], Transformer [12], KEGG [13], Recon X [14], PharmGKB [15], UniProt [16], CTD [17] and TTD [18]), but most of these databases do not include the additional related data and metadata required for in-depth cheminformatics analyses
In a recent study that is most related to the current work, Sedykh et al [24] collected and published a significant amount of data pertaining to substrates and modulators of transport proteins with the aim of building predictive models for several transporters
Summary
Absorption, distribution, metabolism and excretion (ADME) properties of small molecules are vitally important for their function and potential toxicity, understanding their interaction with transport proteins as well as metabolizing enzymes is fundamental to the discovery and development of e.g. safe, efficacious medicines and skin products This data is largely dispersed across the literature, with fractions of the data available in current open and proprietary databases. Tools that convert chemical names into structures (e.g. NCI/CADD Chemical Identifier Resolver [22] or OPSIN [23]) can be used, but due to the complexity of chemical naming they may fail or derive incorrect/inconsistent structures, thorough manual checking of structures is highly beneficial Those few relevant freely and accessible resources that do provide chemical structures for download, such as ChEMBL, HMDB and Drugbank, all have different aims and contents (collections of bioactivity data, metabolite data and drug data, respectively). In a single resource, which is not limited to drugs and only positive results, we include cheminformatics-specific data and functionality and protein tissue expression levels and transporter locations in tissues that are often missing in other comparable databases
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