PubChem (https://pubchem.ncbi.nlm.nih.gov) is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem.

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PubChem 2019 update: improved access to chemical data

Knowledge of therapeutic targets and early drug candidates is useful for improved drug discovery. In particular, information about target regulators and the patented therapeutic agents facilitates research regarding druggability, systems pharmacology, new trends, molecular landscapes, and the development of drug discovery tools. To complement other databases, we constructed the Therapeutic Target Database (TTD) with expanded information about (i) target-regulating microRNAs and transcription factors, (ii) target-interacting proteins, and (iii) patented agents and their targets (structures and experimental activity values if available), which can be conveniently retrieved and is further enriched with regulatory mechanisms or biochemical classes. We also updated the TTD with the recently released International Classification of Diseases ICD-11 codes and additional sets of successful, clinical trial, and literature-reported targets that emerged since the last update. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp. In case of possible web connectivity issues, two mirror sites of TTD are also constructed (http://db.idrblab.org/ttd/ and http://db.idrblab.net/ttd/).

Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics

G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects. Herein, we report GPCRome-wide homology models of unprecedented quality, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability. Based on the strategy of 'Less model - more Xtal', each model exploits both a main template and alternative local templates. This achieved higher similarity to new structures than any of the existing resources, and refined crystal structures with missing or distorted regions. Models are provided for inactive, intermediate and active states-except for classes C and F that so far only have inactive templates. The ligand database has separate browsers for: (i) target selection by receptor, family or class, (ii) ligand filtering based on cross-experiment activities (min, max and mean) or chemical properties, (iii) ligand source data and (iv) commercial availability. SMILES structures and activity spreadsheets can be downloaded for further processing. Furthermore, three recent landmark publications on GPCR drugs, G protein selectivity and genetic variants have been accompanied with resources that now let readers view and analyse the findings themselves in GPCRdb. Altogether, this update will enable scientific investigation for the wider GPCR community. GPCRdb is available at http://www.gpcrdb.org.

GPCRdb in 2018: adding GPCR structure models and ligands.

Illuminating G-Protein-Coupling Selectivity of GPCRs.

Isobaric labeling empowers proteome-wide expression measurements simultaneously across multiple samples. Here an expanded set of 16 isobaric reagents based on an isobutyl-proline immonium ion reporter structure (TMTpro) is presented. These reagents have similar characteristics to existing tandem mass tag reagents but with increased fragmentation efficiency and signal. In a proteome-scale example dataset, we compared eight common cell lines with and without Torin1 treatment with three replicates, quantifying more than 8,800 proteins (mean of 7.5 peptides per protein) per replicate with an analysis time of only 1.1 h per proteome. Finally, we modified the thermal stability assay to examine proteome-wide melting shifts after treatment with DMSO, 1 or 20 µM staurosporine with five replicates. This assay identified and dose-stratified staurosporine binding to 228 cellular kinases in just one, 18-h experiment. TMTpro reagents allow complex experimental designs—all with essentially no missing values across the 16 samples and no loss in quantitative integrity. A set of isobaric labeling reagents called TMTpro enables deep quantitative comparisons of proteome measurements across 16 samples.

TMTpro reagents: a set of isobaric labeling mass tags enables simultaneous proteome-wide measurements across 16 samples.

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators. This update describes content expansion, new features and interoperability improvements introduced in the 10 releases since August 2015. Our relationship matrix now describes ∼9000 ligands, ∼15 000 binding constants, ∼6000 papers and ∼1700 human proteins. As an important addition, we also introduce our newly funded project for the Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb, www.guidetoimmunopharmacology.org). This has been 'forked' from the well-established GtoPdb data model and expanded into new types of data related to the immune system and inflammatory processes. This includes new ligands, targets, pathways, cell types and diseases for which we are recruiting new IUPHAR expert committees. Designed as an immunopharmacological gateway, it also has an emphasis on potential therapeutic interventions.

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The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY

To assess risk of preterm birth, small-for-gestational-age (SGA) at birth, and stillbirth after first booster dose of COVID-19 vaccine (third dose) during pregnancy. We used provincial databases in Ontario to identify all live and stillbirths ≥20 weeks’ gestation (BORN birth registry), linked to COVID-19 vaccination data (vaccine registry). Individuals with an expected date of birth between December 15, 2021 (start of booster dose campaign) and August 31, 2022, who received primary series before pregnancy and became eligible for a booster while pregnant (≥6 months since second dose) were included. We estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for preterm birth (<37 weeks), SGA at birth (<10th percentile), and stillbirth, adjusted for calendar time, health behaviours, sociodemographic and pregnancy-related factors using propensity score methods. Among 31 751 births, 17 890 (56.3%) were born to individuals who had received a booster dose during pregnancy. The cumulative incidence of preterm birth was 7.4% among those who received a booster during pregnancy and 8.6% among those who did not. The risk of preterm birth was not associated with receiving a booster dose during pregnancy (aHR: 0.99, 95% CI 0.90–1.08). Similarly, there was no increased risk of SGA at birth among those receiving vs. not receiving a booster during pregnancy (8.5% vs. 9.8%; aHR: 0.87, 95% CI 0.80–0.95) or stillbirth (0.3% vs. 0.7%; aHR: 0.63, 95% CI 0.44−0.90). Receipt of a booster dose of COVID-19 vaccine during pregnancy was not associated with any increased risk of preterm birth, SGA at birth, or stillbirth. 

http://www.jogc.com/article/S1701216323001950/pdf

Risk of preterm birth, small-for-gestational-age at birth, and stillbirth after receiving a booster dose of COVID-19 vaccine during pregnancy

Objective To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy. Design Population based, retrospective cohort study. Setting Ontario, Canada, from 20 December 2021 to 31 August 2022. Participants Individuals were included if they were pregnant with an expected date of delivery from 20 December 2021 (start date of third dose eligibility for everyone ≥18 years) to 31 August 2022, who had completed the two doses of primary covid-19 messenger RNA vaccine series before pregnancy, and became eligible for a third dose (≥six months since dose two) before the end of pregnancy. Main outcome measures Pregnancy outcomes included hypertensive disorders of pregnancy, placental abruption, caesarean delivery, chorioamnionitis, and postpartum hemorrhage. Fetal and neonatal outcomes included stillbirth, preterm birth, admission to neonatal intensive care unit for >24 h, newborn 5 min Apgar score <7, and small-for-gestational age infant (<10th percentile). We estimated hazard ratios and 95% confidence intervals for study outcomes, treating dose three as a time varying exposure and adjusting for confounding using inverse probability weighting. Results Among 32 689 births, 18 491 (56.6%) were born to individuals who received a third covid-19 dose during pregnancy. Compared with eligible individuals who did not receive a third dose during pregnancy, no increased risks were associated with receiving a third covid-19 vaccine dose during pregnancy for placental abruption (adjusted hazard ratio 0.84 (95% confidence interval 0.70 to 1.02)), chorioamnionitis (0.67 (0.49 to 0.90)), postpartum haemorrhage (1.01 (0.89 to 1.16)), caesarean delivery (0.90 (0.87 to 0.94)), stillbirth (0.56 (0.39 to 0.81)), preterm birth (0.91 (0.84 to 0.99)), neonatal intensive care unit admission (0.96 (0.90 to 1.03)), 5 min Apgar score<7 (0.96 (0.82 to 1.14)), or small-for-gestational age infant (0.86 (0.79 to 0.93)). Conclusion Receipt of a third covid-19 vaccine dose during pregnancy was not associated with an increased risk of adverse pregnancy, fetal, or neonatal outcomes. These findings can help to inform evidence based decision making about the risks and benefits of covid-19 booster doses during pregnancy.

https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000632.full.pdf

Pregnancy, fetal, and neonatal outcomes after a first booster dose of covid-19 vaccine during pregnancy in Ontario, Canada: population based, retrospective cohort study

Liam Bruce

Papers

The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY

Risk of preterm birth, small-for-gestational-age at birth, and stillbirth after receiving a booster dose of COVID-19 vaccine during pregnancy

Pregnancy, fetal, and neonatal outcomes after a first booster dose of covid-19 vaccine during pregnancy in Ontario, Canada: population based, retrospective cohort study