The latest release (version 2024.2) of the IUPHAR/BPS Guide to Pharmacology database has been made. Released on 26th June 2024 this is the second release of the year. The following blog post gives details of the key content updates and website changes. GtoPdb now contains:
- 3,083 human targets, 1,744 of which have curated quantitative ligand interactions.
- 12,730 ligands, 9,292 of which have curated quantitative target interactions.
- 1,995 approved drugs, 1,133 with curated quantitative interactions.
- Clinical use summaries for 3,770 ligands, of which 1,985 are approved drugs.
- A total of 20,949 curated binding constants
- Data curated from over 45,800 references
Curation Update
General protein family updates
The Adrenoceptors family has been widely updated. This includes a completely revised detailed introduction, and additions to ligands, interactions and other tables on all nine of the receptor subtypes pages. The updated material was provided by the Adrenoceptors subcommittee, Roger J. Summers, Martin C. Michel and Jillian G. Baker.
New targets curation
19 new protein targets have been added to the Guide since our last update. They represent molecular targets for cancer, inflammation, immunity, viral infection and Parkinson’s disease. Experimental tool compounds or clinical candidates that modulate protein functions have been curated where available.
TID | Family | Gene | Name | Comment |
3274 | Methyllysine reader proteins | SPIN1 | spindlin 1 | Overexpressed in malignancies, making it a target for anti-cancer drug development- two inhibitors tool compounds curated (MS8535, MS31) |
3275 | Coronavirus (CoV) proteins | n/a | CoV Non-structural protein 10 | subunit of the betacoronavirus 2′-O-methyltransferase (mRNA capping enzyme) |
3276 | Coronavirus (CoV) proteins | n/a | CoV Non-structural protein 16 | subunit of the betacoronavirus 2′-O-methyltransferase (mRNA capping enzyme) |
3277 | Coronavirus (CoV) proteins | n/a | CoV 2′-O-methyltransferase (complex) | Target for coronavirus antivirals- sinefungin curated as an inhibitor |
3278 | Gasdermins (GSDM) | GSDMD | gasdermin D | Inflammasome component & pyroptosis effector. Target for the development of drugs with anti-inflammatory effects. disulfiram and LDC7559 curated as inhibitor tools. |
3279 | High Mobility Group (HMG) proteins | HMGB1 | high mobility group box 1 | Endogenous ligand for Toll-like receptors 2 and 4, and RAGE- inhibitor tools 3-AESA and methotrexare curated |
3280 | NF-kappa B TF proteins | RELA | RELA proto-oncogene, NF-kB subunit | Key to regulating the interferon response to SARS-CoV-2 infection- 2 inhibitor toll compounds curated |
3281 | NF-kappa B TF proteins | NFKB1 | nuclear factor kappa B subunit 1 | dimerises with RELA to form most abundant NF-kB TF, promotes expression of genes that drive the immune response and acute phase responses to infection and tissue trauma |
3282 | NF-kappa B TF proteins | NFKB2 | nuclear factor kappa B subunit 2 | Transcriptional activator or repressor of genes involved in inflammation and the immune response |
3283 | NF-kappa B TF proteins | REL | REL proto-oncogene, NF-kB subunit | Involved in apoptosis, inflammation and the immune response- can be oncogenic |
3284 | NF-kappa B TF proteins | RELB | RELB proto-oncogene, NF-kB subunit | RelB-NFκB/p50 and RelB-NFκB/p52 heterodimers are transcriptional activators |
3285 | Synuclein proteins | SNCA | synuclein alpha | Two anti-SNCA mAbs that block toxic synuclein alpha oligomer/fibril formation have been curated |
3286 | Synuclein proteins | SNCB | synuclein beta | non-amyloid component in Alzheimer’s disease plaques |
3287 | Synuclein proteins | SNCG | synuclein gamma | Third member of this small protein family |
3288 | N6-methyladenosine readers | YTHDC1 | YTH N6-methyladenosine RNA binding protein C1 | target for the development of cancer therapeutics- selective inhibitor curated |
3289 | M28: Aminopeptidase Y | QPCTL | glutaminyl-peptide cyclotransferase like | Small molecule gQC inhibitors offer an approach to promote tumour-specific immunity- 4 inhibitors curated |
3290 | Hydrolases & Lipases | LYPLA1 | lysophospholipase 1 | Synthetic and natural product tool inhibitors curated |
3291 | Hydrolases & Lipases | LYPLA2 | lysophospholipase 2 | Synthetic and natural product tool inhibitors curated |
3292 | RAB subfamily | RAB32 | RAB32, member RAS oncogene family | RAB32 S71R identified as a risk factor in familial Parkinson’s disease, in same pathway as LRRK2 activation |
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 562 ligands tagged in GtoPdb as ‘antibacterial’ and 537 of these have links to compounds at ADB. Since our last release we have added 25 new antibacterial ligands including:
- 6 drugs that are approved, or have been approved in the past, for clinical use in human
- 13 compounds that progressed to clinical evaluation
Website Updates
- Updated data download files
- Updated version of our endogenous/natural ligand pairings and detailed endogenous/natural ligand pairings files. Please access from our downloads page.
- ChEMBL
- The pharmacology search tool and our ligand activity charts now use the latest version of ChEMBL (version 34) – updated from ChEMBL 32.