Database Release 2023.2

Posted on August 7, 2023 by guidetopharmacology — Leave a comment

The latest release of the IUPHAR/BPS Guide to Pharmacology database was made on 7th August 2023. This database release is version 2023.2, and is the second release this year. The following blog post gives details of the key content updates and website changes. GtoPdb now contains:

3,039 human targets, 1,695 of which have curated quantitative ligand interactions.
12,163 ligands, 8,959 of which have curated quantitative target interactions.
1,918 approved drugs, 1,107 with curated quantitative interactions.
Clinical use summaries for over 3,494 ligands of which 1,910 are approved drugs.
A total of 20,139 curated binding constants
Data curated from just under 44,000 references

Curation Update

Since our last release in April we have added 14 new protein targets with clinical relevance, that have been identified from primary literature. They all have associated ligands which are also new additions. The majority of these new targets are being investigated for applications in different cancers as you can see in the table below.

Target ID	Name	Therapeutic area
3230	DNA polymerase theta	oncology
3231	DNA polymerase beta	oncology
3232	BCL3 transcription coactivator	oncology
3233	F-box protein 3 (E3 ligase component)	inflammation
3234	Cbl proto-oncogene B	oncology
3235	S-phase kinase associated protein 2 (E3 ligase component)	oncology
3236	ketohexokinase	metabolic disease
3237	axin 2	oncology
3238	phospholipid scramblase 1	viral infection
3239	glutathione peroxidase 4	oncology
3240	TEA domain transcription factor 1	oncology
3241	TEA domain transcription factor 2	oncology
3242	TEA domain transcription factor 3	oncology
3243	TEA domain transcription factor 4	oncology
3244	DDB1 and CUL4 associated factor 1 (DCAF1)	novel E3 ligase for targeted protein degradation applications (e.g. PROTAC development)

A range of new ligands have been added. In addition to new information contributed by our target family subcommittees, additional sources for new ligands include primary med chem literature, patents, company pipeline analysis, INN lists, structure disclosures from scientific meetings and scanning of clinical trials for novel disease-associated agents.

Our PROTACs, molecular glues and other degraders ligand family (https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1030) has been expanded to over 90 experimental and investigational compounds, which in total target over 45 mainly human proteins, but we have two PROTACS that target the coronavirus 3CL-protease (Mpro).

Since our last update we have annotated 22 newly approved drugs – 15/22 are fully curated in the Guide. The other 7 don’t meet our selection criteria (e.g. target is non-human or is non-protein, imaging reagent, non-specific MMOA).

22 newly approved drugs, 15 added to the GtoPdb
Ligand ID	INN	Trade name	Type	FDA Approval date	Indication	Other Approval date
n/a	tofersen	Qalsody	nucleotide	25/04/2023	To treat amyotrophic lateral sclerosis in adults who have a SOD1 gene mutation	n/a
12653	keverprazan		sm	n/a	To treat reflux oesophagitis and duodenal ulcer	15/02/2023 (China)
n/a	pegunigalsidase alfa-iwxj	Elfabrio	pep	09/05/2023	To treat confirmed Fabry disease	04/05/2023 (EMA)
10422	fezolinetant	Veozah	sm	13/05/2023	To treat moderate to severe hot flashes caused by menopause	n/a
n/a	perfluorhexyloctane	Miebo	inert sm	18/05/2023	To treat signs and symptoms of dry eye disease	n/a
11442	epcoritamab-bysp	Epkinly	mAb	19/05/2023	To treat R/R DLBCL and HGBL	n/a
n/a: 12693	sulbactam; durlobactam	Xacduro	sm	23/05/2023	To treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex	n/a
11503; 8804	nirmatrelvir; ritonavir	Paxlovid	sm	25/05/2023	To treat mild-to-moderate COVID-19 in adults at high risk for progression to severe COVID-19	2021 (UK), 2022 (EMA)
n/a	flotufolastat F 18	Posluma	sm	25/05/2023	To use with positron emission tomography imaging in certain patients with prostate cancer	n/a
8312	sotagliflozin	Inpefa	sm	26/05/2023	To treat heart failure	26/04/2019 (EMA; T1DM)
12757	glofitamab-gxbm	Columvi	mAb	15/06/2023	To treat DLBCL or LBCL)	n/a
9559	ritlecitinib	Litfulo	sm	24/06/2023	To treat severely patchy hair loss (alopecia areata)	n/a
9801	rozanolixizumab-noli	Rystiggo	mAb	27/06/2023	To treat antibody positive generalized myasthenia gravis	n/a
12013	somatrogon-ghla	Ngenla	pep	27/06/2023	To treat growth failure due to inadequate secretion of endogenous growth hormone	14/02/2022 (EMA)
n/a	nirsevimab-alip	Beyfortus	mAb	17/07/2023	To prevent respiratory syncytial virus (RSV) lower respiratory tract disease in infants	31/10/2022 (EMA)
9846	mirikizumab	Omvoh	mAb	n/a	Induction and maintenance therapy for ulcerative colitis	27/03/2023 (Japan)
11182	concizumab	Alhemo	mAb	n/a	To treat hemophilia B	2023 (Canada)
5658	quizartinib	Vanflyta	sm	20/07/2023	To use as part of a treatment regimen for newly diagnosed acute myeloid leukemia that meets certain criteria (ie FLT3-ITD +ve)	2019 (Japan)
n/a	cantharidin	Ycanth	sm	21/07/2023	To treat molluscum contagiosum	n/a
n/a	lotilaner	Xdemvy	sm	25/07/2023	To treat Demodex blepharitis	n/a
12858	zuranolone	Zurzuvae	sm	04/08/2023	To treat postpartum depression	n/a
12857	avacincaptad pegol	Izervay	nucleotide	05/08/2023	To treat geographic atrophy (secondary to AMD)	n/a

Antibacterial Curation

We are pleased to report that the Global Antibiotic Research and Development Partnership (GARDP; https://gardp.org/) has extended their funding of our collaboration with Antibiotic DB (ADB; www.antibioticdb.com) for a further 2 years. Through this interaction, GtoPdb provides chemistry and pharmacology for a curated set of antibacterial compounds with links to ADB.

Currently we have 471 ligands tagged in GtoPdb as ‘antibacterial’ and 455 of these have links to compounds at ADB. The antibacterials in the GtoPdb include approved drugs, WHO essential Medicines-listed medicines and a number of investigational and experimental compounds.