Database Release 2024.4

The latest release (version 2024.4) of the IUPHAR/BPS Guide to Pharmacology database has been made. Released on 4th December 2024 this is the fourth release of the year. The following blog post gives details of the key content updates and website changes. GtoPdb now contains:

• 3,089 human targets, 1,750 of which have curated quantitative ligand interactions.
• 12,950 ligands, 9,392 of which have curated quantitative target interactions.
• 2,038 approved drugs, 1,140 with curated quantitative interactions.
• Clinical use summaries for 3,876 ligands.
• 23,474 curated interaction, 21,330 which are quantitative.
• Data curated from over 46,431 references

In this release, 60 new curated interactions have been added.

So far in 2024 826 new curated interactions have been added to the database, along with updates to 341 existing interactions.

Curation Update

New targets curation

We have added 3 protein targets since release 2024.3. These are supported with evidence of pharmacological tool modulators, and were added in conjunction with our natural products curation project.

Approved drugs

Since the 2024.3 release the FDA have approved 9 more drugs, bringing the total for the year so far to 49.

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

Coronavirus antiviral development

Continuing to follow developments towards pan-coronavirus antivirals we have added new inhibitors SS148  and CoV nsp16 inhibitor 2a [PMID: 34257831].

These compounds inhibit both of the CoV methyltransferases (nsp16 and nsp14) that are essential for viral RNA capping and enabling the virus to evade immune detection in humans. SS148 has demonstrated broad-spectrum activity across human coronaviruses in vitro.

Curation of nucleic acid class drugs

We now have all 18 of the currently approved drugs in this class in the GtoPdb. Unfortunately, for many of these we are unable to provide chemical structures, and are restricted to the available nucleic acid sequence information. We have added new fields to present both the sequences and targets for each of these drugs. In line with all of our other approved drugs we curate approval information (dates, indications, trade names etc). We are continuing to add drugs from this class that are clinical candidates in phase 1-3 development.

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 613 ligands tagged in GtoPdb as ‘antibacterial’ and 589 of these have links to compounds at ADB. 260 are approved drugs. Since our last release we have added 18 new antibacterial ligands including:

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

Website Updates

A reminder of some new pages and updates made at our last release (2024.3):

• 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.