Open Access Pharmacology Database Supports Scientific Discovery

The International Union of Basic and Clinical Pharmacology (IUPHAR) Guide to PHARMACOLOGY is a searchable open access database for chemists and pharmacologists that focuses on pharmacological targets (the biochemical entity to which a drug first binds in the body to elicit its effect) and their ligands (substances that bind to receptors, which are a type of pharmacological target). Family-level overviews and more in-depth individual descriptions, curated by experts, provide pharmacological, biological, structural, and genetic properties of selected targets, with entries supplemented by links to PubMed and various relevant databases (e.g., DrugBank, Entrez Gene, PubChem, etc.). While the main audience for the database is practicing chemists and pharmacologists and students in those fields, it is open to anyone interested in this research. This in-depth, high-quality resource is a great addition to pharmacy and chemistry library database lists and guides.

Product Overview/Description

The Guide to PHARMACOLOGY (commonly abbreviated to GtoPdb) serves as a single entry point to information on pharmacological targets and their ligands, focused primarily on human data. GtoPdb offers concise summaries of target families, which contain expert overviews and key references, including “Gold-standard” selective ligands, clinically used drugs, endogenous ligands, probes (radioligands and PET ligands where available), and G protein-coupled receptors (see Figures 1–3).

The database was created in 2011 through a collaboration between the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). It is maintained by a team at the University of Edinburgh led by Professor Jamie A. Davies and updated quarterly by an international network of approximately 560 scientists organized across 100 subcommittees. The information, though only provided in English, is not location specific.

Among other things, GtoPdb aims to:

• Foster innovative drug discovery
• Provide an integrated educational resource that supports high-quality training in the principles and techniques of basic and clinical pharmacology
• Provide access to data on all known biological targets

User Experience

While not intuitive for a beginner user, GtoPdb does provide a navigation tour of the website. It is a well-documented site and is updated regularly. There is no account to sign up for or ability to save searches. To conduct a basic search of the site, you can browse a list of fields or search by a ligand or target’s name, keyword, identifier, or ligand structure (see Figure 4).

Advanced search is broken up into three sections: receptor and other targets, ligand, and pharmacology.

You can limit the Receptor and Other Target search by species (human, mouse, and rat) as well as target type (including interactions, immunopharmacology, immuno process, immuno cell types, imunno disease, associated protein, physiological function, and seventeen other limit options). It is also possible to upload up to 7,500 identifiers, including external database identifiers or gene names (e.g. Entrez Gene ID or HGNC-approved symbol), by file or by copy-and-pasting in the search box.

Ligands are searchable by name or by limiting to one of three topics: ligands, interactions, or immunopharmacology. You can also upload or copy and paste up to 7,500 chemical identifiers. To search for data by literature reference, you can enter title keyword, author name, or PubMed ID. Finally, you can search for compounds by chemical structure, substructure, Structural Molecular Access Representation for Chemical Topology (SMARTS), similarity, and identity .

In both the target search and the ligand search, the % (percent sign) is the wildcard character.

Lastly, you can use the pharmacology search tool to search by target. You can upload or copy and paste into the search box a set of target IDs (e.g. UniProtKB accessions, Ensembl Gene IDs), again limited to 7,500 identifiers, to retrieve a list of ligands known to modulate them.

GtoPdb provides for download the most commonly requested types of data files (CSV, TSV, and an API containing data from the Guide to PHARMACOLOGY in ese). You can email GtoPdb for other data and file formats or download the entire database.

Contracting and Pricing Provisions

The guide’s funding is easily findable and transparent: it is open access with core funding and oversight provided by IUPHAR and BPS as well as various grants. Previously, it was funded by the Wellness Trust. The database is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Because of its imperative to promote drug discovery and the funding sources, it is most likely to stay open access.

Authentication Models

NA

Competitive or Related Products

GtoPdb ligand information, including structure, peptide sequences, clinical data, and nomenclature, links to chemistry resources in PubChem. Additionally, GtoPdb is extensively referenced and linked to primary literature in PubMed.

LigTMap, an open-access, online server, would be a great complement to GtoPdb. It has a fully automated workflow that can identify protein targets of chemical compounds among therapeutic proteins extracted from the PDBbind database. LigTMap is freely accessible at https://cbbio.online/LigTMap, and its source code is released on GitHub (https://github.com/ShirleyWISiu/LigTMap) using the BSD 3-Clause License to encourage re-use and further developments (Shaikh et al., 2021). I’m impressed by how well these open access tools build on each other to advance scientific discovery.

While alternatives exist, the IUPHAR/BPS Guide to PHARMACOLOGY is a singular resource that provides expert curation with a focus on pharmacological data and drug targets.

Critical Evaluation

GtoPdb has multiple strengths: it is highly vetted by volunteer expert reviewers; it is updated regularly and well cited; and it connects with PubMed and PubChem. The primary drawback is in user experience. The site is somewhat difficult to navigate, although it does include documentation on how to search and multiple help guides. Another drawback is that it is only available in English.

A review of Web Content Accessibility Guidelines (WCAG) 4.1.2 standards highlights issues with navigation, color contrast, alt-image, and more. GtoPdb has quite a bit of catching up and correcting to do in order to become fully accessible.

Recommendation

Because of its expert reviews, its frequently updated information, its detailed target and ligand information, and its mandate to drive further discovery, I recommend this database for practicing and student chemists and pharmacologists. It should be added to the list of resources in chemistry and pharmacology library guides, with the caveat that it is not fully accessible according to WCAG 4.1.2 criteria.

References

Shaikh, F., Tai, H., Desai, N., & Siu, S. (2021). LigTMap: ligand and structure-based target identification and activity prediction for small molecular compounds. Journal of cheminformatics, 13(1), 44. https://doi.org/10.1186/s13321-021-00523-1