IUPHAR/BPS Guide to Pharmacology Database Report - December 2025

IUPHAR/BPS Guide to PHARMACOLOGY Database Report December 2025 www.guidetopharmacology.org [email protected] 1 Introduction 4 Key Updates / Notifications 4 The Guide to Pharmacology Database (GtoPdb) 5 GtoPdb Website Analytics 5 Download Statistics 7 GtoPdb Content 8 GtoPdb Entity Growth 9 GtoPdb Updates 9 Targets 9 Ligands 11 Concise Guide to Pharmacology 13 Analysis of journals contributing to curated data 14 AntibioticDB and Global Antibiotic Research and Development Partnership 16 GtoPdb Web-Application Developments 17 Drug Approvals 17 Chemical structure search - highlighting substructures 18 Connectivity 19 Links to other resources 19 Pubchem Connectivity 20 PubChem Statistics for GtoPdb 21 NCBI LinkOuts 21 Europe PMC 22 EBI UniProtKB/Swiss-Prot cross-references 23 HGNC 25 GPCRdb 25 Bibliometrics 26 Nucleic Acids Research Database Issue 26 Concise Guide to Pharmacology 26 CGTP and NAR Citations 26 SARS-CoV-2 Review 27 Other citation metrics 27 General overview of database team activities 29 GtoPdb Team Interactions 29 Global Core Biodata Resource 29 ELIXIR 29 Publications 30 Outreach and Social Media 30 BlueSky 30 X (formerly Twitter) 30 LinkedIn 30 Guide to Pharmacology Blog 30 2 Hot Topics 31 Slides 31 Engaging with Us 31 3 Introduction This database report provides an overview of recent progress and the current status of the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) since our last NC-IUPHAR meeting held in April 2025. Previous reports are online on our downloads page. Here are direct links to our most recent reports: Apr 2025, Nov 2024, Apr 2024 and Nov 2023. We have reduced redundancy between the reports by purging sections without significant changes. Thus, if you remember any aspect that is not here, it may well be in a previous report (and by all means enquire). Zenodo repository of reports: ● April 2025 doi: 10.5281/zenodo.15342610 ● November 2024 doi: 10.5281/zenodo.14046004 ● April 2024 doi: 10.5281/zenodo.11046804 ● November 2023 doi: 10.5281/zenodo.1007801 Key Updates / Notifications ● 2 Database release (2025.2, 2025.3) ○ 374 new ligands ○ 41 new and updated approved drugs ○ 19 new targets added ○ Overall, 570 new ligand-target interactions added, 467 of which are quantitative ● ~38,200 Engaged Sessions per month ● ~26,000 Active users per month 4 The Guide to Pharmacology Database (GtoPdb) GtoPdb Website Analytics We use Google Analytics GA4 to monitor access to the Guide to Pharmacology website and here we report users' access for the 12 months between 1 Dec 2024 and 30 Nov 2025. The graph and table below show access stats, split by country. There are two quite obvious spikes in traffic to the GtoPdb site. The first, from Singapore, approximately between late-June 25 and mid-July 25, with tail-off into August and September. The second, from China, from mid-August 2025 and early-October 2025. Given the very low engagement rate from Singapore (~3% compared to +80% from other countries), the spike from Singapore could well be unfiltered bot traffic. Google Analytics AI advisor identified this as a likely cause, supported by the fact the combination of a huge increase in "Direct" traffic and a "(not set)" landing page is often a sign of automated bots that are not being filtered out by Google Analytics. 5 Singapore The table on the left splits Singapore users by month. The spike in users and sessions in June-August was not matched by an increase in engaged sessions, further supporting that this traffic was automated bots. Whereas the less pronounced increase in September and October was reflected in increased engaged sessions - which may indicate an increase in genuine users. China The spike from China, while certainly unusual for GtoPdb, may not necessarily be a consequence of unfiltered automated bot. The table to the right splits China users by month. The increase in users and sessions is matched by an increase in engaged sessions show - which may indicate an increase in genuine users. This is further supported by the fact that the primary landing page from China was our homepage, indicating traffic to be more likely from human users. 6 The above table summarises the access statistics for the Guide to Pharmacology over the last year, comparing against our previous reporting period (Apr 2024 - Mar 2025). The adjusted figures use revised access stats that remove data from Singapore from mid-June to mid-August to account for the likely unfiltered automated bot traffic. It also uses typically average figures (taken for Jan 25 - Jul 25) for China instead of the recorded figures from August-October 2025 to account for the unusual spike. ** In this report we give pages per engaged session compared to pages per session and views per active user compared to views per users in the last report, The website has had between 2.5-2.8 million page views during the last 12 months. The adjusted access figures show slight decline from previous reporting periods, with engaged sessions, active users and page views all lower than previously reported. However, including all data from China, shows a strong increase in traffic in terms of users and engaged sessions. The average session duration though in the non-adjusted figures 7 Monthly statistics Dec 2024 - Nov 2025 adjusted (last report figures) Dec 2024 - Nov 2025 non-adjusted (last report figures) Engaged Sessions 37,900 (43,835) 51,717 (43,835) Active Users 29,550 (33,296) 46,963 (33,296) Page views 208,885 (255,809) 238,423 (255,809) Pages / Eng. Session 5.51 (4.87)** 4.61 (4.87)** Avg. Session Duration 00:03:56* (00:03:59) 00:02:48 (00:03:59) Views per Active User 7.07 (7.68)** (8.19) 5.07 (7.68)** This above table shows the access stats by country (ordered by most engaged sessions). This highlights the high number of sessions from China, which when accounted for would put the engaged sessions closer to 454,800. Around 66% of all engaged sessions come from the USA, China, UK and India (up from 54% for the last reporting period). Engaged sessions are sessions lasting longer than 10 seconds, or containing 2 or more screen/page views. The table below shows access stats from countries with a Human Development Index (HDI) of less than 0.8. The Human Development Index (HDI) is a summary measure of average achievement in key dimensions of human development: a long and healthy life, being knowledgeable and having a decent standard of living. The HDI is the geometric mean of normalised indices for each of the three dimensions. Countries with a HDI of 0.8 or above are considered ones with ‘very high human development’. Figures for China use average figures (taken for Jan 25 - Jul 25) instead of the recorded figures from August-October 2025 to account for the unusually high traffic. Total users Engaged sessions Engaged Session per Active User India 37102 48142 1.30 China 26248 92273 3.52 Bangladesh 6697 8194 1.22 Brazil 4945 8316 1.68 Mexico 4894 8394 1.72 Pakistan 3982 4923 1.24 Indonesia 3411 4254 1.25 8 Vietnam 2649 3187 1.20 Egypt 2209 2875 1.30 Thailand 2143 2659 1.24 Philippines 2013 2495 1.24 Colombia 1444 2353 1.63 Iran (Islamic Republic of) 1137 1587 1.40 Nigeria 1064 1294 1.22 South Africa 986 1321 1.34 Iraq 945 1160 1.23 Peru 938 1575 1.68 Ukraine 657 1416 2.16 Jordan 403 620 1.54 Ecuador 392 537 1.37 Total for all HDI <0.8 109,732 204,602 1.86 Around 109,000 users for HDI<0.8 countries have accessed GtoPdb, which covers over 200,000 engaged sessions. This is about 32% of all sessions. If India and China are excluded it is around 64,000 sessions (~10% of all sessions). Previously we had reported around 122,000 users and 160,000 engaged sessions from HDI < 0.8 countries. Download Statistics Data for Dec 2024 - November 2025 shows total file downloads of 7,523 during this period, which is a slight decrease on our previous reporting period (7,927 (Apr 24 - Mar 25)). 9 Enzymes 7 (plus Proteinases by Chris Southan, Kinases by Elena) Nuclear hormone receptors 4 Analysis of journals contributing to curated data The following table and graph show the count of unique articles from journals curated in the GtoPdb. The table is restricted to those journals with over 500 unique curated articles. The graph expands this to all journals with over 200 unique curated articles. Title Count J Med Chem 5125 J Biol Chem 3434 Br J Pharmacol 2087 Mol Pharmacol 1946 Proc Natl Acad Sci USA 1934 J Pharmacol Exp Ther 1844 Bioorg Med Chem Lett 1667 Nature 1321 Eur J Pharmacol 1071 Biochem Biophys Res Commun 931 J Neurosci 799 J Immunol 605 Science 605 Endocrinology 575 Biochem J 563 Nat Biotechnol 558 Bioorg Med Chem 516 16 AntibioticDB and Global Antibiotic Research and Development Partnership Our collaboration with AntibioticDB (ADB; www.antibioticdb.com), which started in 2019, continues with the aim of extending the coverage of antibacterial compounds in GtoPdb and providing comprehensive chemistry and pharmacology for select antibacterials curated within ADB. The Global Antibiotic Research and Development Partnership (GARDP; https://gardp.org/) supports the collaboration with funding in place until May 2026. Currently we have 688 ligands tagged in GtoPdb as ‘antibacterial’ and 665 of these have links to compounds at ADB. 271 of the curated antibacterials are approved drugs. The antibacterials in the GtoPdb include approved drugs, WHO essential Medicines-listed medicines, drugs in clinical development, and a number of investigational and experimental compounds. The focus of recent work has been the curation of antibacterial agents included in the WHO’s report “2023 Antibacterial agents in clinical and preclinical development: an overview and analysis” (https://www.who.int/publications/i/item/9789240094000). For further information about our work with ADB please refer to previous Database Reports. This collaboration has also been described in more detail in our 2022 NAR update: 17 Harding SD, Armstrong JF, Faccenda E, Southan C, Alexander SPH, Davenport AP, Pawson AJ, Spedding M, Davies JA; NC-IUPHAR. The IUPHAR/BPS Guide to PHARMACOLOGY in 2022: curating pharmacology for COVID-19, malaria and antibacterials. Nucleic Acids Research, Volume 50, Issue D1, 7 January 2022, Pages D1282–D1294, https://doi.org/10.1093/nar/gkab1010. PMID: 34718737. As part of our work in curating antibacterial compounds in GtoPdb, we now have a dedicated landing page for antibacterials (https://www.guidetopharmacology.org/GRAC/AntibacterialsForward). This page consolidates information on antibacterials in GtoPdb, providing information on our collaboration with ADB and giving details about our inclusion criteria for curating antibacterials. The page includes a full table of all the antibacterial ligands curated in the database, with hyperlinks to the specific ligand summary pages for each compound. The table has separate tabs that provide information and links for the curated bacterial protein targets, additional resources and for references and further reading. We continue to work with ADB to support the maintenance and development of their website. This includes recent work that provides 2D structure display with a short-term future aim to provide structure-based searching and improved filtering capabilities. GtoPdb Web-Application Developments Drug Approvals Each year, the Guide to Pharmacology Curation Team puts together a list of the latest approved drugs from FDA, EMA and MHRA as well as first-time approvals from other agencies. We have now used this information to build a drug approvals page. This shows these approved drugs, in sortable tables, organised by year of approval. The majority of these drugs are curated in the database, and if so they are hyperlinked to their respective summary pages from the INN in the table. We still list drugs that we don’t curate (because they don’t meet our inclusion criteria), although these will not be hyperlinked. 18 Recently we have improved the drug approval tables to better display the primary targets and include a column showing the approval source (national authorities) and year. The table also includes a tab for 2025, showing the most recent approvals. A screenshot of the drug approval page is shown below: Chemical structure search - highlighting substructures We have updated our chemical structure search to include highlighting the query structure in result sets from a substructure search. This uses Chemistry Development Kit’s (CDK) depict feature and highlight functionality. When a user runs a chemical structure search and sets the type to substructure, the query structure will be highlighted in the results set. The below shows an example of a result set from a substructure search. Showing the query structure highlighted (in cyan). 19 In addition to adding highlighting on substructure searches, we are also implementing the display of the Tanimoto Coefficient value used when a similarity search is run. Connectivity Links to other resources GtoPdb has built many collaborative connections with other resources, many of which are reciprocal. The table below shows the number of ligands and targets with out-links to each of the named resources. The table is not exhaustive, but shows those specialist resources we link with and resources that have reciprocal links back into GtoPdb. We submit GtoPdb ligands (as substances) to PubChem at each database release. One of the strengths of GtoPdb is our regular release cycle, with new database releases approximately every quarter. As a consequence, GtoPdb can often be the first submitter of a substance to PubChem. For example, a query of PubChem for compounds where IUPHAR/BPS GtoPdb is the source and where there is only one depositor, shows 68 compounds as of 28th November 2025. We have a long-standing collaboration with HGNC on shared nomenclature interests and our adherence to mapping HGNC-approved human gene symbols and names to NC-IUPHAR nomenclature. In addition, we have built links between more specialist resources such as GPCRdb. GtoPdb submits data to NCBI via their link-out utility, which indexes our PMIDs (https://pubmed.ncbi.nlm.nih.gov/?term=loprovguidpharm[SB], 33 449 PMIDs) with additional links for genes, nucleotides, and proteins. We also submit to Europe PMC (https://europepmc.org/) through their external links service (https://europepmc.org/LabsLink). Using this service, links are added from Europe PMC articles to related GtoPdb target and ligand data where the article is a reference to a curated pharmacological interaction in GtoPdb. A full list of the 8677 Europe PMC articles with GtoPdb data links (at the time of writing) can be retrieved from 20 https://europepmc.org/search?query=%28LABS_PUBS%3A%221969%22%29. Wherever we have cross-links to other resources, we maintain contacts with the teams concerned and do our best to ensure these are regularly refreshed. Site Ligand Links Site Target Links PubChem 10938 GPCRdb 372 ChEMBL 7060 ChEMBL 2257 Reactome 322 Resolute (SLC) 421 AntibioticDB 665 BioParadigms (SLC) 387 IMGT/mAb-DB 411 HGNC 3133 DrugCentral 1742 NCBI (Entrez) Gene 3132 Wikipedia 3038 Ensembl Gene 3088 CAS Registry 6695 RefSeq Protein 1968 GPCRdb 4326 UniProt 3196 BindingDB 2116 Pubchem Connectivity As mentioned, all GtoPdb ligands are submitted to PubChem after each database release, this gives them a PubChem Substance ID (SID). PubChem Substances are community-provided compounds, and many entries may exist for the same molecule. Each may contain different information about the molecule, depending on the information provided by the submitter. PubChem extracts the unique chemical structures from Substance records (standardisation) and stores them as PubChem Compounds. This means that substance records from different data sources about the same molecule are aggregated in a common Compound record in PubChem. Following our September 2025 database release, 2025.3, all 13,503 ligands in GtoPdb have been submitted to PubChem and therefore have PubChem SIDs. Our PubChem connectivity is enhanced by the addition of curatorial (depositor) comments that we provide when submitting compounds. These depositor comments can be viewed on a substance page at PubChem (see example for azithromycin below). We include ligand general comments, clinical use comments and flagged whether the compound is an approved drug and whether it is tagged as relevant to immunopharmacology, antimalarial pharmacology or antibacterial. 21 Depositor comments section of PubChem SID 178103124. Our blog post from December 2022 illustrates how users can exploit these tags when using PubChem. This was reproduced with kind permission from Dr. Chris Southan’s blog post: Exploiting the Guide to Pharmacology substance (SID) tags in PubChem A more recent blog post by Dr. Chris Southan speak to Exploiting minable connectivity from GtoPdb PubChem Statistics for GtoPdb The stats for the 2025.3 release (with 2025.1 in brackets) are as follows (N.B. the links below can be slow but if they do time out try purging your browser cache). 1. Substances (SID) that we submit to PubChem (refreshing previous submissions) are up to 13,520 (13,143). 2. Those that have defined chemical structures are merged into 11,211 (10,794) Compound Identifiers, CIDs (i.e. small molecules and peptides below ~ 70 residues) 3. From our 10,938 CIDs 9,308 have vendor matches 4. The select "IUPHAR/BPS Guide to PHARMACOLOGY"[SourceName] AND gtopdb_approved [Comment] now retrieves 2,139 SIDs (2,098) which link to 1,850 approved drug CIDs 5. Of our SIDs, 1,543 (1,516) are tagged in GtoImmuPdb and 394 (382) of these are approved drugs 6. Of our CIDs 1,065 are tagged in GtoImmuPdb 7. Of our SIDs, 143 are tagged in GtoMPdb and 25 of these are approved drugs 8. Of our CIDs 140 are tagged in GtoMPdb 9. Of our SIDs, 688 are tagged as antibacterial and 271 of these are approved drugs 22 10. Of our CIDs 671 are tagged as antibacterial 11. We have 2,372 (2,460) structures that ChEMBL does not have, 8,226 (7,810) not in DrugBank. 12. 68 (114) structures where GtoPdb is unique as the source. In most cases this is because we were first to extract the paper or patent and push the ligand structures into PubChem where they get linked to the PubMed entries (see Link out section below). There may be some cases where our stereo configuration is unique (InChIKey) but related to other entries (InChKey inner layer). Inspection of “ Related Compounds” and “Same Connectivity” will indicate this. 13. We continue to curate clinical monoclonal antibodies with the PubChem Substance select "IUPHAR/BPS Guide to PHARMACOLOGY"[SourceName] gtopdb_antibody” returning 460 SIDs. Adding “gtopdb_approved” gives 190. The ability to combine selects and filters of our own PubChem entries, find related linked sets (e.g. pivoting from Substances to Compounds) and compare these to other sources in PubChem becomes very informative and powerful. Users are also reminded that, via the InChIKeys or SMILES strings, any of our ligand downloads (including combinations or parts of) can be cast against PubChem using their Identifier Exchange Service to allow detailed exploration of the extensive PubChem links. Users needing guidance for PubChem interrogations are welcome to contact us. NCBI LinkOuts GtoPdb maintains sets of links in the NCBI LinkOut service, to the Protein, Nucleotide, Gene and PubMed databases. Our links are updated frequently. Below is the count of all NCBI database records that contain ‘LinkOuts’ to GtoPdb. The PubMed count covers all references in the databases including reviews and additional reading for target families. Note that the LinkOut pointers link users back to the database. For various technical reasons associated with NCBI mapping stringencies the three sets of entity links have an element of over-counting with redundancy. However the PubMed links are clean because they are assigned via our own curation. Protein 5,940 Nucleotide 5,887 Gene 8,678 PubMed 33,449 (https://pubmed.ncbi.nlm.nih.gov/?term=loprovguidpharm[SB]) Europe PMC GtoPdb maintains records in the Europe PMC External Links Service. Unlike the larger set of NCBI Outlinks, these publication links are restricted to papers from which GtoPdb interaction data have been curated. These link targets and/or ligands mentioned in the article back to GtoPdb detailed pages. 23 The above figure shows an example of the links from PMID:40140563. Under the ‘Data’ tab on the left-hand side the data cited in the article can be found. This shows 3 links back to GtoPdb ligands and targets. Below shows how these data links navigate users to GtoPdb Target and Ligand pages. 24 As of 28th November 2025 there were 8,677 articles in Europe PMC with links to GtoPdb targets and/or ligands. The EPMC interface query is (LABS_PUBS:"1969") Full URL: https://europepmc.org/search?query=%28LABS_PUBS%3A%221969%22%29 (screenshot below) EBI UniProtKB/Swiss-Prot cross-references Below are the metrics for UniProt 2025_04 chemistry sources. The context for these has been given in previous reports. They provide valuable protein < > chemistry mappings including our own targets where we have curated quantitative ligand interactions of generally < 1uM. Note that SwissLipids curated chemical interactions are for metabolites rather than activity modulators. Even though these sources have different ways of curating, it is informative to compare and contrast. Below is a Venn diagram (taken from our NAR update) showing the comparison of UniProtKB identifiers between GtoPdb, ChEMBL and BindingDB. GtoPdb target overlap with both ChEMBL and BindingDB is extensive, GtoPdb has 67 not in ChEMBL and 179 not in BindingDB. 25 Team member Chris Southan maintains his own (http://cdsouthan.blogspot.com/) where relevant posts include cross-pointers to GtoPdb. Hot Topics An established feature, our Hot Topics in Pharmacology track and highlight new significant papers in pharmacology and drug discovery. These are communicated to us from Subcommittee members or picked up from Social Media. For a selection we commission concise commentaries from our expert contacts. Since the end of March 2025, we have added 150 new hot topic articles. Slides We continue to provide a set of generic slides which can be used by anyone presenting or teaching on GtoPdb and a generic poster which can be printed out in various sizes and taken to meetings or handed out as flyers. Engaging with Us As is implicit from the Social Media section above, it is crucial to extend our external presence and impact. Thus, the more readers of this document who “connect” with us, (via whichever of the channels above they use for their own professional profile) the more our outreach extends. This also has mutual advantages. In particular re-tweets and LinkedIN likes are useful for extending the alerting network for new releases, publications, meeting slide sets and blog posts. Note also that each time you either save one of our publications to your own Mendeley account or mention it in a tweet, blog or PubMed commons comment (but make sure you specify a DOI or PubMed link for the auto-indexing) the Altmetrics score. 32