Hot topics in pharmacology

Recent publications of interest recommended by NC-IUPHAR

2020: Jan
2019: Jul | Aug | Sep | Oct | Nov | Dec

January 2020

Structure of the M2 Muscarinic Receptor-β-Arrestin Complex in a Lipid Nanodisc
(1) Staus DP et al. (2020). Structure of the M2 Muscarinic Receptor-β-Arrestin Complex in a Lipid Nanodisc. Nature, DOI: 10.1038/s41586-020-1954-0. [PMID: 31945772]


Resting State Structure of the Hyperdepolarization Activated Two-Pore Channel 3
(1) Dickinson MS et al. (2020). Resting State Structure of the Hyperdepolarization Activated Two-Pore Channel 3. Proc Natl Acad Sci USA, DOI: 10.1073/pnas.1915144117. [PMID: 31924746]


Impact of commonly used drugs on the composition and metabolic function of the gut microbiota
(1) Vila AV et al. (2020). Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Br J Pharmacol, DOI: 10.1038/s41467-019-14177-z. [PMID: 319533813]


New Chemical Modalities and Strategic Thinking in Early Drug Discovery
(1) Blanco M-J & Gardinier KM et al. (2020). New Chemical Modalities and Strategic Thinking in Early Drug Discovery. ACS Med Chem Lett, doi.org/10.1021/acsmedchemlett.9b00582. [ACS: Article]


Therapies for Rare Diseases: Therapeutic Modalities, Progress and Challenges Ahead
(1) Tambuyzer E et al. (2020). Therapies for Rare Diseases: Therapeutic Modalities, Progress and Challenges Ahead. Nat Rev Drug Discov, DOI: 10.1038/s41573-019-0059-7. [PMID: 31913355]


2019 FDA drug approvals
(1) Mullard A. (2020). 2019 FDA drug approvals. Nat Rev Drug Discov, doi: 10.1038/d41573-020-00001-7. [Nature: News Article]


Hot Topics: Cryo-EM structure of a selective T-type calcium channel blocker bound to the Cav3.1 voltage-gated calcium channel

Jörg Striessnig, University of Innsbruck

Nieng Yan's group has now published the cryo-EM structure of the selective T-type Ca2+ channel blocker Z944 bound to the pore-forming α1-subunit of Cav3.1 T-type Ca2+ channels (1). This nicely adds to recent publications reporting of the high-resolution structures of L-type Ca2+ channel blockers (nifedipine, nimodipine, amlodipine, verapamil, diltiazem) bound to the rabbit Cav1.1 skeletal muscle Ca2+ channel (2) and to the model Ca2+ channel CavAb (Ca2+-selectivity engineered into the bacterial homotetrameric Na+-channel NavAb; 3, 4)... Read the full article on our blog

(1) Zhao Y et al. (2019). Cryo-EM Structures of Apo and Antagonist-Bound Human Cav 3.1. Nature, DOI: 10.1038/s41586-019-1801-3. [PMID: 31766050]

(2) Zhao, Y., Huang, G., Wu, J., Wu, Q., Gao, S., Yan, Z., Lei, J., and Yan, N. (2019). Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca2+ Cell 177, 1495-1506 [PMID: 31150622].

(3) Tang, L., El-Din, T.M.G., Swanson, T.M., Pryde, D.C., Scheuer, T., Zheng, N., and Catterall, W.A. (2016). Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs. Nature 537, 117–121 [PMID: 27556947].

(4) Tang, L., Gamal El-Din, T.M., Lenaeus, M.J., Zheng, N., and Catterall, W.A. (2019). Structural Basis for Diltiazem Block of a Voltage-Gated Ca2+ Mol. Pharmacol. 96, 485–492 [PMID: 31391290].


Relative Selectivity of Covalent Inhibitors Requires Assessment of Inactivation Kinetics and Cellular Occupancy: A Case Study of Ibrutinib and Acalabrutinib
(1) Hopper M et al. (2019). Relative Selectivity of Covalent Inhibitors Requires Assessment of Inactivation Kinetics and Cellular Occupancy: A Case Study of Ibrutinib and Acalabrutinib. J Pharmacol Exp Ther, DOI: 10.1124/jpet.119.262063. [PMID: 31871305]


Fluorescent Ligands: Bringing Light to Emerging G Protein-Coupled Receptor Paradigms
(1) Soave M et al. (2019). Fluorescent Ligands: Bringing Light to Emerging G Protein-Coupled Receptor Paradigms. Br J Pharmacol, DOI: 10.1111/bph.14953. [PMID: 31877233]


Methods to Identify and Optimize Small Molecules Interacting With RNA (SMIRNAs)
(1) Ursu A et al. (2019). Methods to Identify and Optimize Small Molecules Interacting With RNA (SMIRNAs). Drug Discov Today, DOI: 10.1016/j.drudis.2019.06.019. [PMID: 31356880]


The Pharmacology and Therapeutic Applications of Monoclonal Antibodies
(1) Castelli MS et al. (2019). The Pharmacology and Therapeutic Applications of Monoclonal Antibodies. Pharmacol Res Perspect, DOI: 10.1002/prp2.535. [PMID: 31859459]


PROTACs: Great Opportunities for Academia and Industry
(1) Sun X et al. (2019). PROTACs: Great Opportunities for Academia and Industry. Signal Transduct Target Ther, DOI: 10.1038/s41392-019-0101-6. [PMID: 31885879]


December 2019

Structure of the Cardiac Sodium Channel
(1) Jiang D et al. (2019). Structure of the Cardiac Sodium Channel. Cell, DOI: 10.1016/j.cell.2019.11.041. [Cell: Article]


Hot Topics: Deciphering the crystal structure of the leukotriene receptor CysLT2 opens up for improved therapeutics

Magnus Bäck, MD PhD, (@TransCardio), Karolinska Institutet and University Hospital, Stockholm, Sweden; Chairman NC-IUPHAR subcommittee on Leukotriene Receptors)

Leukotrienes are lipid mediators of inflammation, initially recognized for their role in asthma, but also having potent effects in for example cardiovascular and neurological diseases as well as in cancer. The initial pharmacological classification of leukotriene receptors based on antagonist selectivity in smooth muscle was shown to be valid at the gene and protein levels. Following the recent description of the CysLT1 receptor structure, Gusach et al. now describe the crystal structures of the CysLT2 receptor in complex with dual CysLT1/CysLT2 receptor antagonists (1). Read the full article on our blog

(1) Gusach A et al. (2019). Structural Basis of Ligand Selectivity and Disease Mutations in Cysteinyl Leukotriene Receptors. Nat Commun, DOI: 10.1038/s41467-019-13348-2. [PMID: 31811124]


GPR101 Mediates the Pro-Resolving Actions of RvD5n-3 DPA in Arthritis and Infections
(1) Flak MB et al. (2019). GPR101 Mediates the Pro-Resolving Actions of RvD5n-3 DPA in Arthritis and Infections. J Clin Invest, DOI: 10.1172/JCI131609. [PMID: 31793912]


Elucidating the Active δ-Opioid Receptor Crystal Structure With Peptide and Small-Molecule Agonists
(1) Claff T et al. (2019). Elucidating the Active δ-Opioid Receptor Crystal Structure With Peptide and Small-Molecule Agonists. Sci Adv, DOI: 10.1126/sciadv.aax9115. [PMID: 31807708]


A Complex Structure of arrestin-2 Bound to a G Protein-Coupled Receptor
(1) Yin W et al. (2019). A Complex Structure of arrestin-2 Bound to a G Protein-Coupled Receptor. Cell Res, DOI: 10.1038/s41422-019-0256-2. [PMID: 31776446]


November 2019

Chemokine Receptor Crystal Structures: What Can Be Learned From Them?
(1) Arimont M et al. (2019). Chemokine Receptor Crystal Structures: What Can Be Learned From Them?. Mol Pharmacol, DOI: 10.1124/mol.119.117168. [PMID: 31266800]


The Druggability of Solute Carriers
(1) Wang W et al. (2019). The Druggability of Solute Carriers. J Med Chem, DOI: 10.1021/acs.jmedchem.9b01237. [PMID: 31774679]


Hot Topics: New crystal structure of the muscarinic M5 receptor completes the set

Comments by Dr. Fiona H. Marshall, Discovery Research UK, MSD (@aston_fm)

Muscarinic receptors consist of 5 G protein-coupled receptors which along with nicotinic ion channels mediate the effects of acetylcholine. Despite years of research on the role of muscarinic receptors in the brain and periphery the Muscarinic M5 receptor has stood out in contrast to M1 -M4 as one which we know little about. The M5 receptor has a unique and unusual distribution in the brain being enriched in mid brain dopamine neurons and in the cerebellum. A lack of selective chemical tools has hampered our ability to study the function of the receptor. Now Vuckovic et al. have solved the X-ray crystal structure of the M5 receptor in complex with the non-selective antagonist tiotropium in the presence of a conformational stabilizing mutation. Read the full article on our blog

(1) Vuckovic Z et al. (2019). Crystal Structure of the M5 Muscarinic Acetylcholine Receptor. Proc Natl Acad Sci USA, DOI: 10.1073/pnas.1914446116. [PMID: 31772027]


GPR75 Receptor Mediates 20-HETE-signaling and Metastatic Features of Androgen-Insensitive Prostate Cancer Cells
(1) Cardenas S et al. (2019). GPR75 Receptor Mediates 20-HETE-signaling and Metastatic Features of Androgen-Insensitive Prostate Cancer Cells. Biochim Biophys Acta Mol Cell Biol Lipids, DOI: 10.1016/j.bbalip.2019.158573. [PMID: 31760076]


Crystal Structure of Dopamine Receptor D4 Bound to the Subtype Selective Ligand, L745870
(1) Zhou Y et al. (2019). Crystal Structure of Dopamine Receptor D4 Bound to the Subtype Selective Ligand, L745870. Elife, DOI: 10.7554/eLife.48822. [PMID: 31750832]


The human secretome
(1) Uhlen M et al. (2019). The human secretome. Science Signaling, 12 (609) DOI: 10.1126/scisignal.aaz0274. [SciSignalling: Article]


Resistance to Autosomal Dominant Alzheimer's Disease in an APOE3 Christchurch Homozygote: A Case Report
(1) Arboleda-Velasquez JF et al. (2019). 25 (11), 1680-1683 DOI: 10.1038/s41591-019-0611-3. [PMID: 31686034]


In Vivo Validation of a Small Molecule Inhibitor of Tau Self-Association in Htau Mice
(1) Davidowitz EJ et al. (2019). In Vivo Validation of a Small Molecule Inhibitor of Tau Self-Association in Htau Mice . J Alzheimers Dis, DOI: 10.3233/JAD-190465. [PMID: 31771053]


A New Alzheimer’s Approval in China
(1) Lowe D. (2019). In The Pipeline: A New Alzheimer’s Approval in China. Sci Trans Med, 10 May 2019. [In The Pipeline: Article]
(2) Wang X et al. (2019). Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. Cell Res., 29(10):787-803. doi: 10.1038/s41422-019-0216-x. [PMID: 31488882]


Free-Wilson Analysis of Comprehensive Data on Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importance of N-Methylation for PI3Kδ Activity
(1) Barnes L et al. (2019). Free-Wilson Analysis of Comprehensive Data on Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importance of N-Methylation for PI3Kδ Activity. J Med Chem, doi: 10.1021/acs.jmedchem.9b01499. [PMID: 31647659]


An Alzheimer's-disease-protective APOE mutation
(1) Zalocusky KA et al. (2019). An Alzheimer's-disease-protective APOE mutation. Nat Med, doi: 10.1038/s41591-019-0634-9. [PMID: 31686033]


Discovery of ABBV/GLPG-3221, a Potent Corrector of CFTR for the Treatment of Cystic Fibrosis
(1) Scanio MJC et al. (2019). Discovery of ABBV/GLPG-3221, a Potent Corrector of CFTR for the Treatment of Cystic Fibrosis. ACS Med Chem Lett, doi: 10.1038/s41589-019-0387-2. [ACS: Letter]


Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptorsr
(1) Foster S et al. (2019). Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors. Cell, doi: 10.1016/j.cell.2019.10.010. [Cell: Full text]


October 2019

Structure of an allosteric modulator bound to the CB1 cannabinoid receptor
(1) Shao Z et al. (2019). Structure of an allosteric modulator bound to the CB1 cannabinoid receptor. Nat Chem Biol, doi: 10.1038/s41589-019-0387-2. [PMID: 31659318]


Structural basis of species-selective antagonist binding to the succinate receptor
(1) Haffke M et al. (2019). Structural basis of species-selective antagonist binding to the succinate receptor. Nature, 574(7779):581-585. doi: 10.1038/s41586-019-1663-8. [PMID: 31645725]


A Point of Inflection and Reflection on Systems Chemical Biology
(1) Johnson EO & Hung DT. (2019). A Point of Inflection and Reflection on Systems Chemical Biology. ACS Chem Biol, doi: 10.1021/acschembio.9b00714. [PMID: 31613592]


From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9
(1) Petrilli WL et al. (2019). From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9. Cell Chem Biol, pii: S2451-9456(19)30322-8. doi: 10.1016/j.chembiol.2019.10.002. [PMID: 31653597]


A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor
(1) Dekan Z et al. (2019). A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor. Proc Natl Acad Sci USA, 116(44):22353-22358. doi: 10.1073/pnas.1908662116. [PMID: 31611414]


Hot Topics: 3D structure of the full-length P2X7 receptor provides insight into factors controlling agonist potency and receptor desensitisation

Comments by Charles Kennedy, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde

P2X receptors are ligand-gated cation channels for which ATP is the endogenous orthosteric agonist. Seven P2X subunits have been identified and they form trimers to produce at least twelve different receptor subtypes. The tertiary structure of several subtypes have been reported, but they all lack clear information on the conformation of the N- and C-terminal cytoplasmic domains because of the truncated constructs used and the flexibility of these domains. Now, McCarthy et al., (1) report single-particle cryo-EM images of the full-length rat P2X7 receptor in both apo (closed pore) and ATP-bound (open pore) states, which suggest why the affinity of this receptor for ATP is low, indicate how cysteine residues in the C-terminal control desensitisation and reveal a surprising guanine nucleotide binding site in the C-terminal. Read the full article on our blog

(1) McCarthy et al. (2019). Full-length P2X7 structures reveal how palmitoylation prevents channel desensitization. Cell. https://doi.org/10.1016/j.cell.2019.09.017. [ScienceDirect: View Article]


September 2019

A Comparative Assessment Study of Known Small-Molecule Keap1−Nrf2 Protein–Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity
(1) Tran KT et al. (2019). A Comparative Assessment Study of Known Small-Molecule Keap1−Nrf2 Protein–Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity. J Med Chem, 62(17):8028-8052. doi: 10.1021/acs.jmedchem.9b00723. [PMID: 31411465]


Advances and Challenges in Rational Drug Design for SLCs
(1) Garibsingh RA & Schlessinger A et al. (2019). Advances and Challenges in Rational Drug Design for SLCs. Trends Pharmacol Sci, doi.org/10.1016/j.immuni.2019.08.008. [PMID: 31519459]


Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database
(1) Nguengang Wakap S et al. (2019). Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet, doi: 10.1038/s41431-019-0508-0. [PMID: 31527858]


August 2019

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells
(1) Dutertre C-A et al. (2019). Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells. Immunity, doi.org/10.1016/j.immuni.2019.08.008. [Immunity: View Article]


A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity
(1) Tran KT et al. (2019). A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity. J Med Chem, doi: 10.1021/acs.jmedchem.9b00723. [PMID: 31411465]


SEP-363856, A NOVEL PSYCHOTROPIC AGENT WITH A UNIQUE, NON-D2 RECEPTOR MECHANISM OF ACTION
(1) Dedic N et al. (2019). SEP-363856, A NOVEL PSYCHOTROPIC AGENT WITH A UNIQUE, NON-D2 RECEPTOR MECHANISM OF ACTION. J Pharmacol Exp Ther, pii: jpet.119.260281. doi: 10.1124/jpet.119.260281. [PMID: 31371483]


Hot Topics: GPR139 as a potential target for increasing opioid safety

Comments by Simon R. Foster, Monash University and Professor David E. Gloriam, University of Copenhagen and Head of GPCRdb (@David_Gloriam)

The cross-talk between different G protein-coupled receptor signal-transduction pathways is an intriguing concept with important physiological implications [1]. A recent study by Wang et al. [2] has discovered that the actions of opioid drugs on the μ-opioid receptor (MOR) are negatively regulated by an interaction with the undercharacterized GPR139 receptor [3]. These findings implicate GPR139 as a potential target for increasing opioid safety. Read the full article on our blog

(1) Selbie, L. A. & Hill, S. J. G protein-coupled-receptor cross-talk: the fine-tuning of multiple receptor-signalling pathways. Trends in pharmacological sciences 19, 87-93, (1998). [PMID: 9584624]

(2) Wang, D. et al. Genetic behavioral screen identifies an orphan anti-opioid system. Science (New York, N.Y.), eaau2078, (2019). [PMID: 31416932]

(3) Vedel, L., Nohr, A. C., Gloriam, D. E. & Brauner-Osborne, H. Pharmacology and function of the orphan GPR139 G protein-coupled receptor. Basic & clinical pharmacology & toxicology, (2019). [PMID: 31132229]


Over 1,000 genetic loci influencing blood pressure with multiple systems and tissues implicated
(1) Cabrera CP et al. (2019). Over 1,000 genetic loci influencing blood pressure with multiple systems and tissues implicated. Hum Mol Genet, pii: ddz197. doi: 10.1093/hmg/ddz197. [PMID: 31411675]


Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes
(1) Sberro H et al. (2019). Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes. Cell, pii: S0092-8674(19)30781-0. doi: 10.1016/j.cell.2019.07.016. [PMID: 31402174]


Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel

Comments by Jörg Striessnig, University of Innsbruck

In this report the Catterall laboratory succeeded in solving the high resolution structure of a voltage-gated Na+-channel (Nav) in its resting state (1). Why is this difficult and why is this important? It is difficult because Navs exist in the resting state only at very negative voltages but not at a zero membrane potential required for structural analysis by X-ray crystallography or cryo-EM. Accordingly, all high resolution structures of Navs, whether pro- or eukaryotic, have so far reported channels with the voltage-sensing domains in the depolarized state, i.e. the positively charges S4 helices of the voltage sensors moved "up" towards the extracellular side. Therefore it is not known how the activation gate of the ion pore (formed by the four S6 helices) is kept closed by the voltage sensor in its resting position, i.e. with the S4-helices "down". Read the full article on our blog

(1) Wisedchaisri G et al. (2019). Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel. Cell, 178(4):993-1003.e12. doi: 10.1016/j.cell.2019.06.031. [PMID: 31353218]


Identification of a novel allosteric GLP–1R antagonist HTL26119 using structure- based drug design
(1) O'Brien A et al. (2019). Identification of a novel allosteric GLP–1R antagonist HTL26119 using structure- based drug design. Biol Med Chem Lett, doi: 10.1016/j.bmcl.2019.08.015. [ScienceDirect: Abstract]


Visualization of drug target interactions in the contexts of pathways and networks with ReactomeFIViz
(1) Blucher AS et al. (2019). Visualization of drug target interactions in the contexts of pathways and networks with ReactomeFIViz. F1000 Res, doi: 10.12688/f1000research.19592.1. [PMID: 31372215]


Structure and mechanism of the cation-chloride cotransporter NKCC1
(1) Chew TA et al. (2019). Structure and mechanism of the cation-chloride cotransporter NKCC1. Nature, doi: 10.1038/s41586-019-1438-2. [PMID: 31367042]


Building a Hybrid Physical-Statistical Classifier for Predicting the Effect of Variants Related to Protein-Drug Interactions
(1) Wang B et al. (2019). Building a Hybrid Physical-Statistical Classifier for Predicting the Effect of Variants Related to Protein-Drug Interactions. Structure, pii: S0969-2126(19)30200-X. doi: 10.1016/j.str.2019.06.001. [PMID: 31279629]


Revisiting the classification of adhesion GPCRs
(1) Scholz N et al. (2019). Revisiting the classification of adhesion GPCRs. Ann N Y Acad Sci, doi: 10.1111/nyas.14192. [PMID: 31365134]


July 2019

The atlas of aminergic GPCR mutagenesis

Comments by Chris De Graaf (@Chris_de_Graaf)

G protein-coupled receptors (GPCRs) are an important family of signal-transducing membrane proteins capable of binding various types of ligands from the extracellular space and activating various signalling pathways inside the cell, rendering them one of the largest protein target families in pharmaceutical research [1]. Receptors of the aminergic GPCRs family are particularly rewarding drug targets as they are implicated in various disease areas, and structure-based drug design has enabled the understanding of ligand binding and function, and the development of more than 500 approved drugs targeting these receptors. Advances in structural biology allowed the determination of more than 300 crystal structures of more than 60 GPCR subtypes to date [2], however, these still represent only a small fraction of known receptor-ligand associations [3]. Site-directed mutagenesis (SDM) is a versatile and frequently employed tool in pharmacological investigations used to infer structural features of protein-ligand interactions [4]. Mutation studies complement structural information provided by crystal structures by defining the roles and relative importance of residues involved in binding, functional activity, and selectivity for ligand chemotypes which have not yet been co-crystallized with their receptors. Community-wide GPCR structure modelling challenges have shown that the best models could be constructed by careful incorporation of mutation and SAR data relating to ligand binding [5]. However, an integrated analysis of receptor and ligand structures and SAR, mutation data, and binding mode prediction has been so far lacking. The study of Vass et al. can be regarded as a meta-analysis of the site-directed mutagenesis literature for aminergic G protein-coupled receptors [6]. Read the full article on our blog

(1) Santos et al. (2017). A comprehensive map of molecular drug targets. Nat Rev Drug Discov. doi: 10.1038/nrd.2016.230. [PMIDs: 27910877]

(2) Munk et al. (2019). An online resource for GPCR structure determination and analysis. Nat Methods. doi: 10.1038/s41592-018-0302-x. [PMIDs: 30664776]

(3) Vass et al. (2018). Chemical Diversity in the G Protein-Coupled Receptor Superfamily. Trends Pharmacol Sci. doi: 10.1016/j.tips.2018.02.004. [PMIDs: 29576399]

(4) a) Munk et al. (2016). Integrating structural and mutagenesis data to elucidate GPCR ligand binding. Curr Opin Pharmacol. doi: 10.1016/j.coph.2016.07.003. [PMIDs: 27475047] b) Arimont et al. (2017) Structural Analysis of Chemokine Receptor–Ligand Interactions. J Med Chem doi: 10.1021/acs.jmedchem.6b0130. [PMIDs: 28165741]. c) Jespers et al. (2018). Structural Mapping of Adenosine Receptor Mutations: Ligand Binding and Signaling Mechanisms. Trends Pharmacol Sci. doi: 10.1016/j.tips.2017.11.001. [PMIDs: 29203139]

(5) a) Kufareva et al. (2011) Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment. Structure. doi: 10.1016/j.str.2011.05.012. [PMIDs: 21827947]; b) Kufareva et al. (2014). Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges. Structure. doi: 10.1016/j.str.2014.06.012. [PMIDs: 25066135]

(6) Vass et al. (2019). Aminergic GPCR-Ligand Interactions: A Chemical and Structural Map of Receptor Mutation Data. J Med Chem. doi: 10.1021/acs.jmedchem.8b00836. [PMIDs: 30351004]


EPA’s DSSTox Database: History of development of a curated chemistry resource supporting computational toxicology research
(1) Grulke CM et al. (2019). EPA’s DSSTox Database: History of development of a curated chemistry resource supporting computational toxicology research. computational Toxicology, https://doi.org/10.1016/j.comtox.2019.100096. [ScienceDirect: Abstract]


Sharing of clinical trial data and results reporting practices among large pharmaceutical companies: cross sectional descriptive study and pilot of a tool to improve company practices
(1) Miller J et al. (2019). Sharing of clinical trial data and results reporting practices among large pharmaceutical companies: cross sectional descriptive study and pilot of a tool to improve company practices. BMJ, 366:l4217. doi: 10.1136/bmj.l4217. [PMID: 31292127]


New drugs: where did we go wrong and what can we do better?
(1) Wieseler B et al. (2019). New drugs: where did we go wrong and what can we do better?. BMJ, 366:l4340. doi: 10.1136/bmj.l4340. [PMID: 31292109]


A genetics-led approach defines the drug target landscape of 30 immune-related traits
(1) Fang H et al. (2019). A genetics-led approach defines the drug target landscape of 30 immune-related traits. Nat Genet, 51(7):1082-1091. doi: 10.1038/s41588-019-0456-1. [PMID: 31253980]


The human endogenous metabolome as a pharmacology baseline for drug discovery
(1) Bofill et al. (2019). The human endogenous metabolome as a pharmacology baseline for drug discovery. Drug Discov Today, pii: S1359-6446(19)30104-7. doi: 10.1016/j.drudis.2019.06.007. [PMID: 31226432]


Chemokine receptor crystal structures: what can be learnt from them?
(1) Arimont M et al. (2019). Chemokine receptor crystal structures: what can be learnt from them?. Mol Pharmacol, pii: mol.119.117168. doi: 10.1124/mol.119.117168. [PMID: 31266800]


Archive of previous years