Database Release 2023.1

The latest release of the IUPHAR/BPS Guide to Pharmacology database was made on 26th April 2023. This database release is version 2023.1, and is the first release this year. The following blog post gives details of the key content updates and website changes. GtoPdb now contains:

• 3,023 human targets, 1,662 of which have curated quantitative ligand interactions.
• 11,944 ligands, 8,814 of which have curated quantitative target interactions.
• 1,872 approved drugs, 1,098 with curated quantitative interactions.
• Clinical use summaries for over 3,385 ligands of which 1,866 are approved drugs.
• A total of 19,890 curated binding constants
• Data curated from over 43,543 references

Curation Update

Updates have been made to many target family summary pages in preparation for generating the 2023-24 issue of the Concise Guide to PHARMACOLOGY (due for publication at the end of the year). More significant modifications have been made to the summary pages for the GABAA receptors (in Ion channels) and Orexin receptors (in GPCRs). A major overhaul of the Taste 2 GPCRs (Bitter taste receptors) has been completed, with newly annotated details for ligands that interact with these receptors. We thank all of our contributors who have given so freely of their time to make these updates possible.

As a regular review of the INN lists from the WHO, we added 31 new kinase inhibitors to the Guide (see table 1), that were included in the Jan 2023 list of proposed INNs (List 128). The chemical structures allowed us to connect around half of these (16/31) INNs to clinical leads (some with declared name>structure), and others to patents from which we could obtain otherwise unpublished target information and interaction data. Five of the structures matched ligands that were already in the Guide. In total we have found interaction data for 27/31 of these inhibitors. For a few, we were unable to track down very little additional information.

A new set of antivirals for SARS-CoV-2 have been curated, based on patent extractions by our collaborator Chris Southan:

example I-1 [WO2023283831] (12588), TBK845 (12589), example 18 [WO2022013684] (12590), GDI-036 (12591), example 45 [WO2022229458] (12592) and compound 6 [WO2022133588] (12593) are Mpro inhibitors, and PLpro inhibitor 7 (12596) inhibits the other crucial coronavirus protease PLpro. New to this list of antivirals are two PROTAC class protein degraders, both of which target the Mpro for proteosomal degradation; these are CoV Mpro CRBN PROTAC 9 [US11530195] (21594) and CoV Mpro VHL PROTAC 9 [US11518759] (12595).

Keeping up with drug approvals for 2023, there have been 14 new drugs approved by the  FDA since the beginning of the year. The table below provides the ligand IDs for the 11/14 that are curated in the Guide.

Antibacterial Curation

We are pleased to report that the Global Antibiotic Research and Development Partnership (GARDP; https://gardp.org/) has extended their funding of our collaboration with Antibiotic DB (ADB; www.antibioticdb.com) for a further 2 years. Through this interaction, GtoPdb provides chemistry and pharmacology for a curated set of antibacterial compounds with links to ADB.

Currently we have 425 ligands tagged in GtoPdb as ‘antibacterial’ and 413 of these have links to compounds at ADB. The antibacterials in the GtoPdb include approved drugs, WHO essential Medicines-listed medicines and a number of investigational and experimental compounds.

Web-Application & Database Update

We have updated the version of ChEMBL used on the website. This is now at ChEMBL version 32. On the Guide to Pharmacology website we use data from ChEMBL to supplement both our pharmacology search and ligand activity charts.

We have updated our PubChem CID outlinks – updating ~380 links some of which had been to deprecated CIDs.

We have also done a check and update of our Ensembl out-links, updating deprecated ID/links in a number of cases.