We are pleased to announce our first database release of 2020 – version 2020.1. Coronavirus (Covid-19) We have added a new coronavirus page to the Guide to Pharmacology which aims to consolidate key pharmacological information and resources related to coronavirus.…
Melatonin targets two high-affinity receptors, MT1 and MT2, that belong to the G protein-coupled receptor (GPCR) superfamily (1,2). Drugs acting on melatonin receptors are subscribed for circadian disorders (jet lag, shift work, etc.), insomnia and major depression (3). All marketed…
Thirty eight years after the discovery that injection of the catalytic subunits of cyclic AMP-dependent protein kinase A (PKA) into isolated pig ventricular cardiac myocytes (1) increases the amplitude of L-type Ca2+ current (today known to be formed by Cav1.2…
Two new reports cover further aspects of cannabinoid receptor binding as defined using cryo-EM. These expand on previous reports of the structure of the human CB1 cannabinoid receptor with the antagonists taranabant and AM6538 bound, and with the agonists MDMB-FUBINACA,…
The new respiratory coronavirus from Wuhan in China is causing intense research activity in the world. Viruses are evidently associated with respiratory infections ranging in severity from the common cold to pneumonia and death
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…
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…
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…
Our fifth and final database release of 2019 has been made and includes a number of minor content and website updates. Crucially, it comes at a time when we have just published our most recent database update in Nucleic Acids…
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…
We are delighted to announce the first full public release of the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (abbreviated to GtoMPdb). This new web resource, designed specifically for malaria pharmacology, has been developed as a joint initiative between the International Union…
We are very pleased to announce our a new release of the IUPHAR/BPS Guide to Pharmacology. This version (2019.4) is the fourth this year and includes the first full-release of the IUPHAR/MMV Guide to Malaria Pharmacology. Content Updates GtoPdb now…
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…
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…
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…
We have now made the third IUPHAR/BPS Guide to Pharmacology database release of 2019 (2019.3). It includes updates focussed on preparation for the next edition of The Concise Guide to PHARMACOLOGY (2019/20), due out later this year. Content Updates GtoPdb…
G protein coupled receptors (GPCRs) are crucial for the transduction of extracellular stimuli to the intracellular space. Upon activation, GPCRs undergo large conformational changes to engage transducers and stimulate intracellular responses. However, the kinetics of agonist induced GPCR conformational changes…
Thursday 25th 2019 is World Malaria Day and we’d like to highlight our new resource, currently under development, called The IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb). Based in Edinburgh, this new resource is directed by Professor Jamie Davies and his team and…
A recent commentary in Nature has the provocative title “Retire Statistical Significance” (1, with a list of more than 800 signatories) and has been widely interpreted as a call for the entire concept of statistical significance to be abandoned. Closer…
We are pleased to announce a new IUPHAR/BPS Guide to Pharmacology database release! This release, 2019.2, is the second of the year and includes updates focussed on preparation for the next edition of The Concise Guide to PHARMACOLOGY (2019/20), due…
We are pleased to make public the first beta-release (v1.0) of the Guide to MALARIA PHARMACOLOGY (GtoMPdb), a new extension to the existing Guide to PHARMACOLOGY (GtoPdb). The GtoMPdb is being developed as a joint initiative between Medicines for Malaria…
Whilst life is always exciting as an ion channel pharmacologist, the last few months have been particularly so, with a large number of publications showing structures of ion channels with regulatory molecules bound to them. In just the last month,…
New machine learning algorithm for drug discovery that is twice as efficient as the industry standard and identified potential ligands for the M1 receptor, a potential target for the treatment of Alzheimer’s disease. A paper from Lee et al. [1]…
G protein-coupled receptors (GPCRs) transduce physiological and sensory stimuli into appropriate cellular responses and mediate the actions of one-third of drugs. Structures of GPCRs are therefore extremely valuable for understanding basic receptor function and rational drug design. Today, 310 structures…
Our first database release of 2019 (2019.1) is now available. This update contains the following new features and content changes: Content Updates GtoPdb contains over 9,400 ligands, with around 7,200 have quantitative interaction data to biological targets. Just over 1,400…
Cannabinoid receptors respond to multiple endogenous fatty acid derivatives and are often divided into neuronal-associated CB1 receptors and immune cell-associated CB2 receptors. Both receptors are GPCR, coupled predominantly to Gi, and have cytoprotective properties. The predominant psychotropic agent in Cannabis, THC,…
The IUPHAR/BPS Guide to Pharmacology was represented at the recent BPS Pharmacology 2018 meeting (London, UK, 18-20 Dec 2018). Tuesday 18th Dec On Tuesday we had two significant presentations. Firstly, a late-breaking poster on the IUPHAR/MMV Guide to Malaria Pharmacology.…
Comments by Dr. Nicola J. Smith, National Heart Foundation Future Leader Fellow & Group Leader, Molecular Pharmacology Laboratory, Victor Chang Cardiac Research Institute, Australia As is often the case with orphan GPCRs, assigning the endogenous ligand has been controversial for the…
A new facet of the human brain has been reported [1] involving a first example of somatic gene recombination in neurons, representing a normal neural mechanism whose disruption could underlie the most common (sporadic) forms of Alzheimer’s disease. Mosaic and…
The cellular thermal shift assay (CETSA) was introduced in July of 2013 as a means to investigate drug target engagement inside live cells and tissues (1). The underlying principle of CETSA is simple – it relies on the thermostability of…
At the beginning of October 2018 we held a meeting in Edinburgh focussed on the launch of the IUPHAR Guide to IMMUNOPHARMACOLOGY. Invited speakers contributed to productive discussions on the varying challenges and opportunities in immunopharmacology research. Immunopharmacology: The New…
Prof. Tracy Hussell Lung Disease: think about disease in a different way Tracy Hussell is Director, Manchester Collaborative Centre for Inflammation Research (MCCIR) and Professor of Inflammatory Disease, University of Manchester, Oxford Road, Manchester, M13 9PT. To be healthy is…
Piezo channels (Piezo1 and Piezo2) are excitatory ion channels which respond directly to a variety of forms of mechanical stimuli. Two recent papers describe some of the critical roles of Piezo channels in sensory neuron transduction (1, 2). In the…
The receptor tyrosine phosphatase (RTP) family is a relatively small group of cell-surface proteins with a simple intracellular enzymatic function in the dephosphorylation of phosphotyrosine proteins. There is less known about the endogenous extracellular ligands which regulate RTP activities in…
The unfortunate French clinical trial disaster in which the FAAH inhibitor BIA 10-2747 (ligand ID 9001) left one participant dead and several others with serious neurological adverse events, occurred back in January 2016. However, the primary publication that describes the properties…
In this multi-author, multi-centre publication [1] lead by Denise Wootten and Patrick Sexton from the Monash Institute of Pharmacological Sciences, there is reported a 3.3 Angstrom structure of one of the more unusual G protein-coupled receptors. The CGRP receptor is…
This paper [1] extends previous studies demonstrating a key role of voltage-gated L-type Ca2+ channels in the modulation of activity-dependent gene transcription. Earlier work in cultured neurons had already shown that L-type channel activity is required to activate gene expression…
Our fourth database release of the year, 2018.4, is now available (n.b. the PubChem update statistics and link sets will be posted in a couple of weeks). This update contains the following new features and content changes: Content Updates GPCRs:…
July 2018 News, Updates and Hot Topics Database release 2018.3: Our third database release of the year, 2018.3, is now available. This update contains the following new features and content changes: Updates across several target classes. The existing Antimalarial targets…
The potassium channels KV7.2-KV7.5 (KCNQ2-5; GtoPdb target IDs 561-564) regulate neuronal excitability in the mammalian nervous system. The best characterised neuronal KV7 channels give rise to the M current (1) and are mediated predominantly by hetero-tetramers of KV7.2 and KV7.3…
A new type of deorphanization conundrum confronted in pairing the GPCR, MAS1 with the hormonal peptide angiotensin 1–7 (Ang1-7) was emphasised in recent IUPHAR reviews (1, 2). More evidence for disconnection between Ang1-7 and MAS1 is presented in the recent…
Every few years in the field of receptor pharmacology, a technological advance occurs that drives the field forward in terms of insight and understanding. Over the past couple of years, the cryo-EM technique (the development of which won the 2017…
What will Systems Biology look like in the future? Up to now, it has focussed on the development of standards, software tools and databases that enabled us to study the dynamics of physiological function mechanistically. However as these tools and…
The A1 adenosine receptor is, for most people, a molecular target they can become conscious of when they block it, which happens frequently. Rapid consumption of higher doses of caffeine, in products like Italian espresso or Turkish coffee, provokes a…
Our third database release of the year, 2018.3, is now available. This update contains the following new features and content changes: Content updates GPCRs: Adenosine receptors Chemokine receptors Cholecystokinin receptors Dopamine receptors Ghrelin receptors Opioid receptors GPR55 receptors NHRs: MRetinoic…
The Cannabis plant is a natural product from which more than 100 apparently unique metabolites (cannabinoids) have been identified. Many of these have been found in human plasma following consumption of Cannabis preparations. The most well-recognised is tetrahydrocannabinol, THC, because…
As some of our contacts may know, we hold hemi-annual meetings between IUPHAR, BPS the GtoPdb team, together with invited guests from our collaborators and NC-IUPHAR committee representatives. Covering ~ 2.5 days these usually take place in Paris or Edinburgh.…
19 June 2018 update. Announced only about a week after the events described below, yet a third clinical candidate, lanabecestat (AZD-3293, LY3314814) has also bitten the dust (4). The two PhIII trials were stopped because they were deemed unlikely to meet their…
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…
The A2A adenosine receptor is densely expressed in dopamine-rich areas of the brain and in the vasculature. It is the target of an adjunct medication for Parkinson’s Disease, istradefylline in Japan, an A2A receptor antagonist. The A2A adenosine receptor is an example…
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