The latest release (version 2025.1) of the IUPHAR/BPS Guide to Pharmacology database has been made. Released on 2nd April 2025 this is the first release of the year. The following blog post gives details of the key content updates and website changes. GtoPdb now contains:
- 3,097 human targets, 1,758 of which have curated quantitative ligand interactions.
- 13,131 ligands, 9,485 of which have curated quantitative target interactions.
- 2,098 approved drugs, 1,175 with curated quantitative interactions.
- Clinical use summaries for 3,996 ligands.
- 23,652 curated interaction, 21,491 which are quantitative.
- Data curated from over 47,009 references
In this release, 181 new ligands, 178 new curated interactions have been added.
Curation Update
New targets curation
We have added 8 protein targets since release 2024.3, summarised in the table below:
| TID | Family | Gene | Name | Comment |
| 3299 | Neuropilins and Plexins | PLXND1 | plexin D1 | Involved in axon guidance. Expression upregulated in prostate cancer, drives aggressiveness, invasiveness, and drug resistance. A preclinical synthetic PlexinD1:Fc decoy fusion protein (D1SP) is curated (oncology) |
| 3300 | Sortilin family proteins | SORT1 | sortilin 1 | Blocking sortilin 1 activity increases progranulin (PGRN) in a preclinical model of frontotemporal dementia and in patients- ? Translation to reduced disease progression. Two anti-SORT1 mAbs curated (neurodegeneration) |
| 3301 | CD33-related SIGLECs | SIGLEC6 | sialic acid binding Ig like lectin 6 | Considered as a therapeutic target for the treatment of eosinophil- and mast cell-mediated inflammation- development of anti-SIGLEC6 mAb discontinued at phase 1 (lack of efficacy) |
| 3302 | Thioredoxin (Trx) system proteins | TXNRD1 | thioredoxin reductase 1 | thioredoxin antioxidant system- overexpression is associated with drug resistance and poor prognosis in several types of cancer. Inhibitors hyperactivate ROS production -> ER stress and apoptosis. Synthetic and NP inhibitors curated (oncology) |
| 3303 | Tumour-associated antigens | STEAP1 | STEAP family member 1 | Antigen highly expressed on prostate cancer and metastases, functions in cell-cell junctions. Anti-STEAP1 mAb curated (oncology) |
| 3304 | T-box transcription factors | TBXT | T-box transcription factor T | Aka brachyury- oncogenic in chordoma (a bone cancer) – inhibitor compound curated (oncology) |
| 3305 | WD repeat-containing proteins | SIGLEC6 | NACHT and WD repeat domain containing 1 | Novel target for metabolic dysfunction-associated steatohepatitis (MASH) (metabolic disease) |
| 3306 | Lymphocyte antigens | LY75 | lymphocyte antigen 75 | Differentially expressed in malignancies from various histotypes- rapidly internalises so good target for delivery of cytotoxic agents to tumour cells- ADC OBT076 (maytansinoid microtubule disruptor payload) curated (oncology) |
Ligands
In total, 180 new ligands have been added to the GtoPdb since the last update in December 2024 (release 2024.4). These include synthetic small molecules, antibacterials, antibodies, peptides and natural products.
Our list of approved drugs for 2024 was expanded to a total of 61. This set includes first approvals from regulatory agencies other than the FDA and EMA, such as China’s NPMA and Japan’s PMDA. 7 of the new approvals are not included as fully-curated ligand entries as they fall out with our inclusion criteria. Presentation of this set of drugs on the website is discussed in more detail below, in the database development section.
The new WHO INN proposed list 132 (PL132) was published in mid-February 2025.
Of the 249 INNs, 54 are curated in the GtoPdb; 24 existed under alternate names and were matched on chemical structures to the INNS. A further 30 (the majority of which are kinase inhibitors) are brand new entities for the GtoPdb, and where possible the structures are matched to internal company IDs (even speculatively when no name-structure has been formally disclosed), patent claims, target-specific quantitative data and clinical trials. The INN secutrelvir was matched to the Shionogi SARS-CoV-2 Mpro inhibitor S892216.
GtoPdb ligands that have INNS from PL132 are listed in tables 1 and 2 below.
Table 1: INNs from PL132 for kinase inhibitors that are in the GtoPdb
| LID | INN |
| 8204 | rizavasertib |
| 12625 | veludacigib |
| 12703 | ubavitinib |
| 12711 | gozanertinib |
| 12903 | tersolisib |
| 13267 | famlasertib |
| 13297 | cirtociclib |
| 13371 | silevertinib |
| 13731 | alnodesertib |
| 13732 | andamertinib |
| 13733 | atebimetinib |
| 13734 | balomenib |
| 13735 | birelentinib |
| 13736 | catadegbrutinib |
| 13740 | pruvonertinib |
| 13741 | perzebertinib |
| 13742 | emupertinib |
| 13743 | engasertib |
| 13744 | enozertinib |
| 13746 | lasmotinib |
| 13747 | lirucitinib |
| 13750 | lomonitinib |
| 13751 | pasodacigib |
| 13752 | tosposertib |
| 13753 | romaciclib |
| 13754 | zeltociclib |
| 13806 | fosizensertib |
| 13808 | claturafenib |
| 13809 | dabogratinib |
| 13811 | dirozalkib |
Table 2: INNs from PL132 in the GtoPdb for miscellaneous protein targets
| LID | INN |
| 11116 | olisutrigine bromide |
| 11514 | solangepras |
| 11859 | tetrandrine |
| 11946 | palacaparib |
| 11953 | ceperognastat |
| 12116 | navlimetostat |
| 12622 | elironrasib |
| 12802 | vilagletistat |
| 12895 | nedizantrep |
| 12902 | vopimetostat |
| 12973 | elunetirom |
| 13002 | fudapirine |
| 13241 | xeruborbactam isoboxil |
| 13320 | ralometostat |
| 13368 | daraxonrasib |
| 13552 | zalsupindole |
| 13737 | ratutrelvir |
| 13738 | secutrelvir |
| 13739 | rugocrixan |
| 13745 | larubrilstat |
| 13798 | adimanebart |
| 13800 | balertatug |
| 13802 | becondogrel |
| 13803 | darlifarnib |
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 648 ligands tagged in GtoPdb as ‘antibacterial’ and 628 of these have links to compounds at ADB. 267 are approved drugs. Since our last release we have added 34 new antibacterial ligands including:
-
- 3 drugs that are approved, or have been approved in the past, for clinical use in human
We are developing a new landing page for antibacterials in the Guide to Pharmacology and this will be publicly available as part of a future database release.
Website Updates
Drug Approvals summary page
We have developed a new page that records details of drug approvals. https://www.guidetopharmacology.org/GRAC/DrugApprovalsForward
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. The new drug approval page, shows these approved drugs in table, organised by year of approval. The majority of these drugs will be curated in the database, and if so they are hyperlinked to their respective summary pages from the INN in the table. There are some cases were we have listed an approved drug but it doesn’t have a link because it will not have been curated.
guidetopharmacology blog 
Leave a comment