Database Release 2024.3

The latest release (version 2024.3) of the IUPHAR/BPS Guide to Pharmacology database has been made. Released on 3rd October 2024 this is the third release of the year. The following blog post gives details of the key content updates and website changes. GtoPdb now contains:

• 3,086 human targets, 1,747 of which have curated quantitative ligand interactions.
• 12,862 ligands, 9,356 of which have curated quantitative target interactions.
• 2,019 approved drugs, 1,138 with curated quantitative interactions.
• Clinical use summaries for 3,825 ligands, of which 2,008 are approved drugs.
• A total of 21,268 curated binding constants
• Data curated from over 46,200 references

In this release, 119 new curated interactions have been added.

So far in 2024 761 new curated interactions have been added to the database, along with updated to 338 existing interactions.

Curation Update

New targets curation

3 new protein targets have been added to the Guide since our last update.

New ligand curation

A range of new ligands have been curated from analysis of INN proposed list 131 (August 2024)

In total 28 synthetic small molecules with INNs in this list are now included in the GtoPdb; 6 matched chemical structures that were already in our data set (the top 6 in the table below), and 22 are brand new entries (LIDs >13480). Where possible the INNs have been linked to (probable) company research codes, corroborating publications, quantitative interaction data, and clinical trials. 18/28 are kinase inhibitors, 2 are EZH2 inhibitors, 1 is a PROTAC, and the others are intended to modulate a range of therapeutic targets including SLC6A19, cannabinoid, orexin and opioid receptors, COX-2 and autotaxin. Analysis is continuing to identify any of the monoclonal antibodies that are directed against proteins that are not already included in the GtoPdb, to expand our coverage of emerging drug targets.

Use the Ligand ID link to view the ligand at the Guide to Pharmacology

Approved drugs

With access to the EMA’s master EPAR download file restored (it had been unavailable since Dec 2023), we were able to retrospectively update the EU approval data for >30 drugs. In addition, the FDA has approved 16 new drugs since our last update, 14 of which meet the inclusion criteria for the GToPdb.  We have also included 2 new drugs that were approved in jurisdictions outside of the US and EU.

Antibacterial Curation

Our collaboration with Antibiotic DB (ADB; www.antibioticdb.com) continues to allow us to extend the coverage of ligands with annotated antibacterial activity in GtoPdb and provide comprehensive chemistry and pharmacology for select antibacterials curated within ADB, via reciprocal links. This project is supported by the Global Antibiotic Research and Development Partnership (GARDP; https://gardp.org/).

Currently we have 594 ligands tagged in GtoPdb as ‘antibacterial’ and 566 of these have links to compounds at ADB. 255 are approved drugs.

Since our last release we have added 31 new antibacterial ligands including:

• • 3 drugs that are approved, or have been approved in the past, for clinical use in human

Website Updates

• Nucleic acid ligands
  • We have re-classified a small number of ligands as ‘nucleic acids’ and made this a new ligand category (https://www.guidetopharmacology.org/GRAC/LigandListForward?type=Nucleic-acid).
• Natural products
  • A new landing page (https://www.guidetopharmacology.org/GRAC/NaturalProductsForward) for natural products in the Guide to Pharmacology is available.  This is part of the collaboration between IUPHAR (https://iuphar.org/) and the Italian Society of Pharmacology (SIF; https://www.sifweb.org/) to provide an expert-driven project to curate NPs as a resource within the Guide to Pharmacology.