Blog Archives

Hot topic: GPR3 and GPR6, novel molecular targets for cannabidiol

Cannabidiol is a major metabolite from the Cannabis plant, although levels vary dependent on genetic, regional, cultivation and other factors.  It lacks the psychotropic nature of THC, but has been reported to have many biological effects, to the extent that

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Hot topic: Selectivity determinants of GPCR–G-protein binding

As a detailed comparative sequence/structure/evolution analysis it is relatively unusual (in a good sense) to see such a bioinformatics article in Nature. This tour de force was a collaboration between MRC Laboratory of Molecular Biology, Cambridge UK and the Department

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Hot topics: Crystal structure of full-length glucagon receptor provides insight into relative orientation of extracellular and transmembrane domains in an inactive conformation and importance of dynamic changes in this orientation for activation

It has been quite challenging to gain high resolution structural insights into an intact class B G protein-coupled receptor, despite previous solution of multiple structures for the two dominant domains, the extracellular domain (ECD) and the transmembrane helical bundle domain

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Hot topics: Crystal structure of GLP-1 receptor transmembrane domain provides insight into allosteric modulation.

The glucagon-like peptide-1 receptor (GLP-1R) is a major target for treatment of Type 2 diabetes but has been refractory to the development of small molecule compounds as potential therapeutics. Song et al., (1) report the first crystal structures of the GLP-1R

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Guide to IMMUNOPHARMACOLOGY – beta release v1.0, May 2017

We are pleased to announce the first, public, beta-release of the Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb). The GtoImmuPdb is a Wellcome Trust-funded extension to the existing Guide to PHARMACOLOGY (GtoPdb) and the beta-release (v1.0) marks an important milestone in its production and development. GtoImmuPdb aims to provide improved data exchange between immunology and pharmacology expert communities, […]

Posted in Guide to Immunopharmacology

Database release 2017.4

Our 4th database release of 2017 was published on 23rd May 2017. It now includes 15133 interactions between 2813 targets and 8900 ligands. For full release statistics see the Guide to PHARMACOLOGY About page. Target Updates Updates have been made to

Posted in Database updates, Guide to Immunopharmacology, Technical

Hot topics: New crystal structure of the full-length Smoothened reveals ligand-dependent interaction between extracellular CRD and the 7TM core of the receptor

Molecular details of receptor activation remain scarce when it comes to Class Frizzled receptors and even less is known about the dynamics between the N-terminal cysteine rich domain (CRD) and the transmembrane domain (TMD) in the absence and presence of

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Hot Topics: Protein-phospholipid interplay revealed with crystals of a calcium pump

Ca2+-ATPases are members of the P-type transporters and are usually regarded as post-stimulus recovery mechanisms, allowing calcium ions to be removed from the cytosol either via re-accumulation into sarcoplasmic/endoplasmic reticulum (the SERCA pumps) or extrusion outside the cell (the PMCA

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Hot Topics: New developments in cryo-electron microscopy reveal the first Class B GPCR active structure in complex with a G protein

The last 10 years has seen a huge increase in the numbers of X-ray structures solved for GPCRs. However solving fully active structures in complex with G proteins remains challenging. Recent advances in cryo-electron microscopy (cryo-EM), including improved direct electron

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Hot Topics: Fish peptide treats cardiovascular disease

The novel GPCR peptide ligand Elabela/Toddler (APELA, Ela), first identified in the fish Danio and critical for the development of the heart, has now been identified in the human cardiovascular system. Yang et al. [1] have recently showed that the

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Hot Topics: Neurokinin 3 receptor antagonism for menopausal hot flushes

Neurokinin B signalling is increased in menopausal women and has been implicated as an important mediator of hot flushes. A phase 2 trial has assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901). Results showed it safely and

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Hot Topics: Crystal structures of human AT2 reveal molecular mechanism for lack of desensitization and internalization

The intracellular signal transduction processes activated by the angiotensin AT2 receptor, are atypical for a GPCR and different from the AT1 receptor. Although the classic motifs a GPCR are present in AT2 receptor; it fails to demonstrate classic features of

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Hot Topics: Structural insights into adiponectin receptors suggest ceramidase activity

Adiponectin receptors, divided into Adipo1 and Adipo2, were initially classed as GPCR on the basis of hydropathy analysis suggesting seven transmembrane domains.  However, they appear to be present in the cell membrane in a topology inverted compared to the 7TM

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GtoImmuPdb: technical update March 2017

The 4th alpha-release (v4.0) of the Guide to IMMUNOPHARMACOLOGY was released on 23rd March 2017. This blog post summarises some of the main features of the release and other developments as we moved toward our first public, beta-release in Spring

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Database release 2017.2

Our 2nd database release of 2017 was published on 23rd March 2017. It now includes 15019 interactions between 2809 targets and 8832 ligands. For full release statistics see the About the Guide to PHARMACOLOGY page. Target updates The major part

Posted in Concise Guide to Pharmacology, Database updates, Technical

Recent IUPHAR reviews on Ang(1-7) coupling with GPCRs, treating systemic autoimmune diseases, and small molecule modulators of adenylyl cyclases

The latest ‘state of the field’ IUPHAR reviews are out in the British Journal of Pharmacology: Karnik SS, Khuraijam D, Tirupula K, Unal H. (2017) Significance of Ang(1-7) coupling with MAS1 and other GPCRs to the Renin-Angiotensin System: IUPHAR Review

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Hot Topics: Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1

Despite a flurry of mammalian ATP binding cassette (ABC) transporter structures in the last 2 years the Holy Grail has still been to determine how these diverse proteins interact with their transport substrates. Jue Chen and colleagues at the Rockefeller

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GtoImmuPdb: technical update February 2017

The 3rd alpha-release (v3.0) of the Guide to IMMUNOPHARMACOLOGY was released on 30th January 2017. This blog post summarises some of the main features of the release and other developments as we moved toward our first public, beta-release in Spring

Posted in Guide to Immunopharmacology, Technical

Citation profiles for our NAR and Concise Guide papers

Posted in Publications

Database release 2017.1

We are pleased to announce our first database release of 2017 on 26th Jan 2017. While there are no major updates in this release, it includes several bug fixes and new ligands of relevance to immunopharmacology. Our new portal, the

Posted in Database updates, Technical

IUPHAR review 100 in Pharm Revs and review 21 in BJP

NC-IUPHAR has just published its 100th review in Pharmacological Reviews

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Hot topics: The orphan GPR139 receptor is activated by peptides

GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression in the striatum and hypothalamus, regions regulating locomotion and metabolism, respectively, and it has therefore been suggested as a

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Hot topics: X-ray crystallographic study defines binding domains for Ca2+ antagonist drugs and their molecular mechanism of action

This year witnessed a tremendous progress in our understanding of the structure-function relationship of voltage-gated Ca2+ channels. This is based on the cryo-electron microscopy structure of the rabbit Cav1.1 Ca2+ channel complex at a nominal resolution of 3.6 Å ([1]

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GtoImmuPdb: technical update December 2016

Our final technical update for 2016 covers our v2.0 alpha-release, presentation at Pharmacology 2016 and future plans.

Posted in Guide to Immunopharmacology, Technical

Hot topics: Will the real splice variants please stand up?

The number of alternative mRNA splice forms that map to human protein coding loci has increased to the point that nearly all proteins have such associated database records. This gives rise to the paradox that the gene build pipeline from

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GtoImmuPdb: technical update November 2016

During October we have made the first alpha-release (v1.0) of the Guide to IMMUNOPHARMACOLOGY. This blog post summarises some of the main features of the release and work on the documentation. This first release marks an important step towards the

Posted in Technical

GtoPdb Ligands in PubChem

GtoPdb and  its precursor IUPHAR-DB have been capturing the structures of pharmacologically relevant ligands since 2005.  The fig.1. snapshot below  shows the approved drug section of our eight-category ligand classification As an active collaboration with the  PubChem team, we have

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Hot topics: X-ray structure of the endothelin ETB receptor

Endothelin is a peptide that acts via two G-protein coupled receptors. ETA mainly causes vasoconstriction. In contrast ETB  predominantly acts as a beneficial clearing receptor and by the release of endothelium derived relaxing factors, vasodilatation [1,2]. This paper  describes for

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Hot topics: Synthesis and SAR for depsipeptide natural products as selective G protein inhibitors

A team including the Gloriam Group at the University of Copenhagen (also the home of GPCRDB) have paper out in Nature Chemistry reporting the first total synthesis of YM-254890 and FR900359 [1] . These are related cyclic depsipeptide natural products that

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Hot topics: X-ray structure of P2X3 receptor

Extracellular ATP is able to activate two families of cell-surface receptors, one of which is the ligand-gated ion channel family of P2X receptors. This family of cation channels is distinct from the remainder of the ligand-gated ion channels, as they

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GtoPdb database release 2016.4

We are pleased to announce our fourth database release of 2016. Version 2016.4 was published on 13th October 2016. The database is available through the Guide to Pharmacology website, download pages and web-services.

Posted in Database updates

Why Data Citation Is a Computational Problem

By Peter Buneman The database development team encouraged me to write this off-topic blog on data citation, as it may be of interest to people involved with the IUPHAR/BPS Guide to Pharmacology (GtoPdb). It must be almost ten years ago

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SynPharm: A New Annexe to the Guide to PHARMACOLOGY

We have created a new sister database to the main Guide to PHARMACOLOGY (GtoPdb) – SynPharm, a database of drug-responsive protein sequences. Each sequence in SynPharm is derived from a GtoPdb interaction. In each case we have identified the continuous

Posted in Technical

GtoImmuPdb: technical update September 2016

The focus of development in the last month has been on preparing the GtoImmuPdb portal for alpha-release and building landing-pages for process and cell type association lists.

Posted in Guide to Immunopharmacology, Technical

Hot topics: High resolution structure of the voltage-gated skeletal muscle Ca2+ channel complex

In a recent article in Nature [1], Wu et al. present the cryo-electron microscopy structure of the rabbit Cav1.1 complex at a nominal resolution of 3.6 Å.

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Hot topics: Allosteric Modulation of Receptor Function and Regulation

Changeux and Christopoulos have recently described in Cell [1] how common mechanisms link the allosteric sites of activation and response within the four major receptor families of ligand- and voltage-gated ion channels, G-protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As

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Hot topics: Analysis of protein-coding genetic variation in humans

Leck et al. in Nature, describes a tour de force largest scale reference data set of high-quality protein-coding variation generated via the Exome Aggregation Consortium (ExAC)

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Hot Topics: Discovery of opioid analgesics with reduced side effects

Manglik et al., writing in Nature, believe they may have found a new form of painkiller that works just as well as morphine but lacks its potentially lethal side effect.

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GtoImmuPdb: technical update August 2016

The major developmental extension to GtoImmuPdb has been incorporation of cell type associations and web-app development to display both process and cell type data.

Posted in Guide to Immunopharmacology, Technical

GtoPdb database release 2016.3

We are pleased to announce our third database release of 2016. Version 2016.3 was published on 21st July 2016. The database is available through the Guide to Pharmacology website, download pages and web-services. In this release, our curators have added comments to all approved

Posted in Database updates

FREE – Concise Guide to Pharmacology 2015/2016

The Concise Guide to PHARMACOLOGY 2015/2016 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to the open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed

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Hot Topics: Linking chemistry to papers

The key value of our curation is the extraction of chemistry-activity-target data from papers.

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GtoImmuPdb: technical update May 2016

Development of the Guide to Immunopharmacology (GtoImmuPdb) continues and this is an update of progress since our last update in February 2016. Since then, the GtoImmuPdb April Meeting was held in Edinburgh, where a detailed update on the status of

Posted in Guide to Immunopharmacology, Technical

Recent DrugBank Changes

The DrugBank database has just announced (09 May 2016) more restrictive access conditions including user registration. Not unexpectedly, this has prompted discussion on Twitter and elsewhere (e.g. ThinkLab. including some from the DrugBank team).  We enjoy long-standing contacts with the

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GtoPdb database release 2016.2

The latest update of the database, version 2016.2, has been released (30th March 2016). The summary of the main updates is below. Database content in various formats can be downloaded from our download pages and accessed via web services. This

Posted in Database updates

Assessment of GtoPdb in-links

A valuable aspect of biological databases in general and the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) in particular, are out-links to and in-links from, other relevant resources.

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GtoImmuPdb: technical update Feb 2016

Technical update from database and curation team behind The Guide to Immunopharmacology

Posted in Guide to Immunopharmacology, Technical

GtoPdb database release 2016.1

Database release 2016.1, now features 14249 curated interactions.

Posted in Database updates

GtoPdb database release 2015.3

Our total number of curated interactions now stands at 13859. New BLAST tool for sequence-based searching of targets available at http://www.guidetopharmacology.org/blast/.

Posted in Database updates

New project to develop “The Guide to Immunopharmacology”

We are very pleased to announce a new initiative (from 1st Nov 2015) to establish “The Guide to Immunopharmacology: Integration of targets, diseases and therapies into an expert-driven database”. This project will be supported by a 3-year grant awarded to

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