Database release 2018.2

Our second database release of the year, 2018.2, is now available. This update contains the following new features and content changes:

Content updates

GPCRs:
5-Hydroxytryptamine receptors
Adenosine receptors
Adrenoceptors
Histamine receptors
Opioid receptors
Lysophospholipid (S1P) receptors
Prostanoid receptors

NHRs:
Mineralocorticoid receptor
Peroxisome proliferator-activated receptors

Channels:
Transient Receptor Potential channels
Na_v1.5

Enzymes:
Nitric oxide synthases
Cyclooxygenase
Phosphodiesterases, 3′,5′-cyclic nucleotide (PDEs)
Cyclin-dependent kinase (CDK) family
Mitogen-activated protein kinases (MAP kinases)
NADPH oxidases

Transporters:
Monoamine transporter subfamily

Others:
Heat shock proteins

New website features

Pharmacology Search Tool

In release 2018.1 we announced a new Pharmacology Search Tool allowing users to upload lists of target ids and find ligands to modulate them. We have now extended this tool to (optionally) search for other relevant ligands in ChEMBL v23. The ChEMBL data has been filtered according to the same rules we use for the ligand activity visualisation charts (see the help documentation for details) and as well as displaying the ChEMBL curated activity values, we also display their calculated -log pChEMBL value. An example of the results returned from this type of search is shown in Fig 1.

Figure 1. Example of results returned from a UniProt Accession search in the Pharmacology Search Tool, showing the top 3 GtoPdb and ChEMBL ligands. Results are ordered by total number of ligands in these databases that match search criteria.

New PDB ligand icon

As part of our increased emphasis on ligand structures (as seen with our synPHARM resource), we have introduced a new ligand icon for PDB entries. We display this on the ligand list and target interaction tables to indicate which ligands have PDB entries (orange circle with a white alpha helix across the centre), as shown in Fig 2.

Figure 2A. The ligand list showing the new PDB ligand icon in orange.

Figure 2B. A target inhibitor table showing the new PDB ligand icon in orange.

Sponsored Tocris product links

We have collaborated with Tocris as a quality supplier of many of the ligands in GtoPdb by adding links from our ligand pages out to the matching Tocris products. An example, which can be found on the ligand page beneath the summary tab, is shown in Fig 3. In total there are links to 1198 Tocris products.

Figure 3. Ligand summary page showing a link to the Tocris product.

Other updates

BJP/BJCP linking

As an adjunct to our successful entity-linking initiative for the BJP and more recently BJCP, we have instigated a process whereby, on manuscript acceptance and their own marking-up of GtoPdb links, authors alert us directly to key entities from their studies that are not in our database. In most cases, we then add the missing ligands. This has the advantages for both the author and the journal of not only adding their reference into GtoPdb but also the paper gains PubChem PubMed reciprocal linking derived from our PubChem ligand submissions. Examples from this release include GS-458967 from BJP and esaxerenone from BJCP.

BACE1 in doubt as an Alzheimer’s drug target

The target entry for the Alzheimer’s drug target BACE1 underwent key updates. The first of these was to add a new reference for the full report published just last week on the Phase III failure of the lead Merck BACE1 inhibitor verubecestat. Unfortunately, this paper now casts doubt on the target validation status and thus the future for this entire class of compounds pursued intensively for over 18 years. Notwithstanding, several ligands on the BACE1 list may yet complete their clinical evaluation (these will be joined by the latest  development candidate from Pfizer as PF-06751979 in 2018.3)

SynPHARM article

We are pleased to report that an open pre-print version (i.e. pending changes compared to the eventually accepted journal version) of our manuscript describing our SynPharm resource is now on-line.

How-to-Guide 

We are also pleased to report the publication of  Accessing Expert‐Curated Pharmacological Data in the IUPHAR/BPS Guide to PHARMACOLOGY. It is not indexed in PubMed yet but note that the PDF is free to access until the end of May (so pull it down while you can! – but we could send you one if you miss the window).  It includes useful examples of how to use both GtoPdb and GtoImmuPdb as a supplement to our online help and FAQ.