Guide to Pharmacology Help Page
ContentsAbout the Guide to Pharmacology
For more information on the Guide to Pharmacology see the About the Guide to Pharmacology page.
The Guide to Pharmacology includes data from the International Union of Basic and Clinical Pharmacology Database (IUPHAR-DB) and the Guide to Receptors and Channels (GRAC) 5th edition (2011).
A tutorial for using the GRAC database and guidance on navigating the web site is available to download as a PDF.
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IUPHAR-DB (www.iuphar-db.org) is developed under the auspices of NC-IUPHAR (International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification) to provide an accurate educative resource to the scientific community. It relies on contributions by expert pharmacologists who volunteer their time. All contributors are attributed on the website, allowing receptor data pages to be properly cited. A direct link to IUPHAR-DB can be found in the top toolbar on every page of the Guide to Pharmacology.
The GRAC database (www.guidetopharmacology.org/GRAC/) was developed in association with NC-IUPHAR based on information from the 5th edition of GRAC published in the British Journal of Pharmacology:
For more information on the GRAC 5th edition (2011) see the British Journal of Pharmacology web site.
These help pages describe the terms and symbols used in the GRAC database and the search tools available on the Guide to Pharmacology web site. For detailed help pages relating to IUPHAR-DB please see the IUPHAR-DB help document.
For further information on the pharmacological terms mentioned see the NC-IUPHAR publication on terms and symbols.
The data are primarily summarised from selected primary literature articles, which are linked to PubMed. Where possible the data are linked to other relevant databases for further information.
A quick text search box is provided in the top tool bar of all pages. Just enter keywords in the text field and press 'Search database' to perform a matching text search on all data fields.
Advanced search tools can be accessed from the drop down menu on the main tool bar. Advanced search tools allow text searches on specific database fields, as well as non-text searches e.g. by accession number or chemical structure. Depending on the type of data you wish to search for you can choose between target search tools and chemical search tools.
Searches will return results from both the GRAC and IUPHAR databases with links to the relevant pages in each database.
Target search tools
Ligand search tools
For all targets; additional information relevant to specific target types is listed below this section.
Nomenclature - The recommended nomenclature for a structurally and operationally distinct target in a given family. Where this is the NC-IUPHAR published recommended nomenclature, this is specified in the Overview section with references to the relevant articles in Pharmacological Reviews. In cases where there are no published NC-IUPHAR recommendations, the adopted nomenclature is usually one of: the HGNC approved gene name, a name commonly used in the literature or a preliminary recommendation from NC-IUPHAR.
Genes and Ensembl IDs - For each target, the human (Hs), mouse (Mm) and rat (Rn) gene symbols are provided with links to the HUGO Gene Nomenclature Committee (HGNC), Mouse Genome Informatics (MGI) and Rat Genome Database (RGD) web sites. Links are also provided to the Ensembl genome database. Further database links can be accessed via IUPHAR-DB target pages. For descriptions of databases linked to see the Database Links table.
Ligand interaction data - Ligand interactions at targets are listed by ligand action, selectivity and ligand context. Where a ligand is endogenous for the target tested, this is indicated accordingly. Ligand names are clickable links to pages describing the ligand's properties (see the Ligand Page section). Ligands are chosen to represent a set of available recommended agonists, antagonists, activators, inhibitors, blockers, allosteric regulators and probes for particular targets. Where possible a summary of the literature recording the ligand's activity are provided. Some data that are provided without references summarise information from references available via the IUPHAR database.
N.B. GRAC focuses on the properties of human targets and data referring to other species are indicated accordingly.
For voltage-gated (VGIC), ligand-gated (LGIC) and other types of ion channels
Ligand interaction data - In some cases ligand interactions at ion channels are listed under the subunit that confers specificity to the heteromeric channel (e.g. nicotinic acetylcholine receptor alpha subunits). Additional supporting information is provided such as subunit/homomer/heteromer selectivity, ligand context and receptor site of action.
Functional characteristics - Provides details of the conductance, voltage-dependence, rectification and selectivity properties of ion channels.
Systematic Nomenclature - The Nuclear Receptor Nomenclature Committee (NRNC) recommended name for the receptor. See reference:
Nuclear Receptors Nomenclature Committee (1999). A unified nomenclature system for the nuclear receptor superfamily. Cell 97, 161-163. [PMID:10219237]
Systematic Nomenclature - The recommended name for the transporter as originally described in a series of reviews published in Pflügers Archives 447, Number 5, February 2004. [PMID:14624363]
Substrates/Endogenous Substrates - Details a list of the substances that are transported. Where the substrate is endogenous for a particular transporter, this is indicated accordingly. Substrate names are clickable links to pages describing the substrate's properties.
Inhibitors/Selective Inhibitors - The inhibitors of a transporter's ability to translocate substrates across the membrane. Where the inhibitor is selective for a particular transporter, this is indicated accordingly. Inhibitor names are clickable links to pages describing the inhibitor's properties.
Stoichiometry/Predicted Stoichiometry - Provides details of the experimentally measured or predicted substrate binding stoichiometry of the transporter together with the direction of substrate translocation across the membrane.
Nomenclature - The nomenclature used here is either recommended by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) (based on the Enzyme Commission (E.C.) number system) or is the HGNC approved name.
E.C. Number - A Enzyme Commission (E.C.) number is a numerical-based classification system for an enzyme based on the reaction it catalyses. Each E.C. number consists of a four-number code, with the first number describing one of 6 possible general enzyme functions: oxidoreductases, transferases, hydrolases, lysases, isomerases or ligases, with the remaining numbers used as an increasingly precise classifier for the enzyme reaction. As E.C numbers describe enzyme function, an E.C number is not necessarily unique to a given enzyme, i.e. an E.C number may be assigned to more than one enzyme, and an enzyme with more than one function may be assigned several E.C numbers.
Substrate/Endogenous Substrate - The substance which a particular enzyme binds to and converts to product. An endogenous substrate originates from the organism in which the given enzyme is being studied, while synthetic substrates include drugs and other non-naturally occurring chemical agents.
Inhibitor/Endogenous Inhibitor - A substance that reduces or prevents the activity of the enzyme, usually by binding to the enzyme. Enzyme inhibitors may be reversible or irreversible, and reversible inhibitors are competitive or non-competitive. Endogenous inhibitors originate from within the organism in which the enzyme is being studied, while synthetic inhibitors include drugs and other non-naturally occurring chemical agents.
2D Structure - An image of the ligand's 2D structure generated using the NCI/CADD Chemical Identifier Resolver. Click on the image to access a chemical structure search tool and pre-load the structure into an editing tool.
Calculated Physico-chemical Properties - Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand:
Ligand classification - Compounds are assigned to general classes based on their origin and structural properties. See the glossary for a list of classes and definitions.
Compounds that are or have been the active ingredients in approved drugs are labelled as such where the information is known. DrugBank drug categories are also provided where possible.
International Nonproprietary Name (INN) - The official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization (WHO). Substances where this compound is an active ingredient are listed.
Species and Gene/Precursor (endogenous peptides) - Species refers to the organism(s) which naturally produce the peptide. Species information is linked to the encoding genes and protein precursor(s) for the peptide (genes and precursors are described for human, rat and mouse where applicable, or other relevant species). A single ligand entry is made where the mature peptide sequence is identical across multiple species. If there is peptide sequence variation across multiple species, then separate ligand entries are made for each species with a different sequence.
Database Links - Provides the accession number and link outs for selected chemical databases, including PubChem, DrugBank, PharmGKB, ChEBI and PDB. For a full list and descriptions see the Database Links table. CAS Registry Numbers are provided where known. CAS Registry Number is a Registered Trademark of the American Chemical Society. Peptide ligand tables include links to genomic and protein databases.
Screening Data - Where there are large scale ligand screening data in the database, these are included in separate tables. Usually a cut-off value is applied so that only targets where the ligand has activity below a particular concentration will be displayed on the ligand page and a link is given to the full set of targets in the screen. Where the screen tested multiple variants of a target the data for the variants are displayed in separately.
Structure Downloads - Various representations of the ligand 2D molecular structure, generated using Open Babel. These are:
Peptide Structure - Peptide ligand pages contain information on the peptide sequence (one and three letter amino acid sequences) with post-translational and chemical modifications detailed where relevant. Where appropriate post-translational and chemical modifications are represented in the three letter amino acid sequences.
Related Sequences (peptides) - Currently this table lists other peptides in the database that have the same parent precursor protein, as well as corresponding peptides from other species, if they are in the database.
Other Similar Sequences (peptides) - This table lists peptides in the database with similar sequences, which may include synthetically-derived and endogenous peptides that are not derived from the same gene or its orthologues. Sequences were clustered using the program h-cd-hit available from the CD-HIT Suite. Peptides were first clustered at a high identity (90%) and the non-redundant sequences were further clustered at a low identity (60%). For details of the methodology see
Ying Huang, Beifang Niu, Ying Gao, Limin Fu and Weizhong Li. (2010) CD-HIT Suite: a web server for clustering and comparing biological sequences. Bioinformatics. 26, 680-682.
Please note that ligand pages are identical between the Guide to Pharmacology and IUPHAR-DB. All ligands can be searched and viewed on either web site.
The default view of the Guide to Pharmacology ligand list includes all ligands described in GRAC and IUPHAR-DB. Separate sublists of ligands in GRAC and IUPHAR-DB can be accessed via links at the top of the page.
|Agonist/full agonist||A ligand that binds to a receptor and alters the receptor state resulting in a biological response. Conventional agonists stabilise an active conformation of a receptor and increase receptor activity. When the receptor stimulus induced by an agonist reaches the maximal response capability of the system (tissue), then it will produce the system maximal response and be a full agonist in that system|
|Inverse agonist||A ligand that by binding to unoccupied receptors reduces the fraction of them in an active conformation. For nuclear receptors, an inverse agonist refers to ligands that can promote co-repressor recruitment|
|Partial agonist||Agonists that in a given tissue, under specific conditions, cannot elicit as large an effect (even when applied at high concentration, so that all the receptors should be occupied) as can another agonist acting through the same receptors in the same tissue|
|Activator||Ligands that activate ion channels by binding directly to them, including ligands that cause a change in the voltage dependence of channel gating that favours activation|
|Antagonist||An antagonist is a drug that reduces the action of another drug, generally an agonist|
|Channel blocker||Ligands that block ion movement through ion channels|
|Inhibitor||Ligands that inhibit ion channel gating by directly binding to the channels, including ligands that inhibit ion channel activation and those that inhibit ion channel inactivation|
|Allosteric regulator||A ligand that increases (positive) or decreases (negative) the action of an agonist or antagonist by combining with a distinct site on the receptor macromolecule. Neutral allosteric ligands bind to an allosteric site without affecting the binding or function of orthosteric ligands but can still block the action of other allosteric modulators that act via the same allosteric site|
|Orthosteric ligand||Ligands that act by binding to the same site as does the physiological agonist of the receptor|
|Potentiation||Refers to the enhancing effect of an allosteric regulator acting at an ion channel|
|Inhibition||Refers to the inhibiting effect of an allosteric regulator acting at an ion channel|
|Radioligand||Radioactive ligands used in receptor binding studies|
|Selectivity||Where a ligand type is selective for a given receptor or ion channel subunit, this is specifically indicated|
|Site of action||In certain ion channels, the particular subunit to which the ligand binds is specified|
|Context||In certain cases, the ligand context (intracellular, luminal, cytosolic or extracellular) is specified|
|Synthetic organics||Low molecular weight, non-polymeric compounds produced via either total synthesis or semi-synthetic processes|
|Metabolites||Low molecular weight, non-peptidic, biogenic compounds produced by life processes (normally endogenous and of animal origin, including hormones and neurotransmitters) and their close analogues|
|Natural products||Non-peptidic, biogenic compounds derived from living organisms and their close synthetic derivatives|
|Endogenous peptides||Peptides encoded in the human, rat and mouse genomes|
|Other peptides||Synthetic, semi-synthetic and natural peptides encoded in genomes other than human, rat and mouse (including oligopeptides and cyclic peptides)|
|Inorganics||Ions and other inorganic compounds|
|Antibodies||Including therapeutic monoclonal antibodies.|
|Others||Silicones and other non-carbon containing molecules and polymers|
|Ligand structural information and properties|
|SMILES||(Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings|
|Canonical SMILES||SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications|
|Isomeric SMILES||SMILES include chiral and isotopic specification|
|InChI standard identifier||(IUPAC International Chemical Identifier) InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching|
|InChI standard key||An InChI Key is a simplified version of a full InChI, designed for easier web searching|
|Calculated Physico-chemical Properties||Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK Toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand.|
|Nomenclature||The recommended nomenclature for a structurally and operationally distinct target in a given family. Where this is the NC-IUPHAR published recommended nomenclature, this is specified in the Overview section with references to the relevant articles in Pharmacological Reviews. In cases where there are no published NC-IUPHAR recommendations, the adopted nomenclature is usually one of: the HGNC approved gene name, a name commonly used in the literature or a preliminary recommendation from NC-IUPHAR.|
|Principal transduction||Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK Toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand.|
|Functional Characteristics||Provides details of the conductance, voltage-dependence, rectification and selectivity properties of ion channels|
|Hs, Mm, Rn||Indicates the species of the target. Hs: Homo sapiens; Mm: Mus musculus; Rn: Rattus norvegicus|
|Experimental measures of ligand action|
|EC50||The molar concentration of an agonist that produces 50% of the maximal possible effect of that agonist. Other percentage values (EC20, EC40, etc.) can be specified. The action of the agonist may be stimulatory or inhibitory|
|IC50||This term is used in a number of ways: (i) the molar concentration of an antagonist that reduces the response to an agonist by 50%; the concentration of agonist should be given; (ii) the molar concentration of an unlabeled agonist or antagonist that inhibits the binding of a radioligand by 50%; the concentration of radioligand should be given; (iii) the molar concentration of an inhibitory agonist that reduces a response by 50% of the maximal inhibition that can be attained; this latter usage is not recommended-instead the term, EC50, should be used since this is an agonist effect|
|KB||KB refers to the equilibrium dissociation constant of a ligand (traditionally, a competitive antagonist) determined by means of a functional assay|
|Kd||Kd refers to the equilibrium dissociation constant of a ligand determined directly in a binding assay using a labeled form of the ligand|
|Ki||Ki refers to the equilibrium dissociation constant of a ligand determined in inhibition studies. The Ki for a given ligand is typically (but not necessarily) determined in a competitive radioligand binding study by measuring the inhibition of the binding of a reference radioligand by the competing ligand of interest under equilibrium conditions|
|Km||The Michaelis constant (Km) defines the concentration of substrate at which the reaction rate is half of the maximum rate (Vmax) achieved by the system at maximum substrate concentrations.|
|pA2||pA2 The negative logarithm to base 10 of the molar concentration of an antagonist that makes it necessary to double the concentration of the agonist needed to elicit the original submaximal response obtained in the absence of antagonist|
|pEC50||The negative logarithm to base 10 of the EC50 of an agonist|
|pIC50||The negative logarithm to base 10 of the IC50 of an agonist or antagonist|
|pKB||The negative logarithm to base 10 of the KB|
|pKd||The negative logarithm to base 10 of the Kd|
|pKi||The negative logarithm to base 10 of the Ki|
|pKm||The negative logarithm to base 10 of the Km|
|Concentration range||Where affinity data are not available, the concentration range of ligand used for the study is displayed (in M)|
|Rank order of potency||The order of potency of the activity of a series of ligands at a particular target|
|Rank order of affinity||The order of substrate binding strength for a particular enzyme|
|HGNC||The authoritative source of approved human gene names and symbols. HGNC approves a unique and meaningful name for every known human gene based on a query of experts.|
|RGD||Provides access to the most current, complete set of rat genomic and genetic data available, as well as the most innovative tools for analyzing this data.|
|MGD||Includes data on mouse gene characterization, nomenclature, mapping, gene homologies among mammals, sequence links, phenotypes, allelic variants and mutants, and strain data.|
|Ensembl||Provides a centralised resource for geneticists, molecular biologists and other researchers studying eukaryotic genomes. It is able to automatically generate graphical views of the alignment of genes and other genomic data against a reference genome.|
|KEGG BRITE||A collection of hierarchical classifications representing various aspects of biological systems.|
|Entrez Gene||Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.|
|UniGene||A database of the transcriptome providing information on protein similarities, gene expression, cDNA clones, and genomic location.|
|OMIM||A database that catalogues all the known human diseases with a genetic component, links them to the relevant genes, references and tools for genomic analysis.|
|RefSeq||A database providing an annotated and curated collection of publicly available nucleotide sequences (DNA, RNA) and their protein products, with separate and linked records for the genomic DNA, the gene transcripts, and the proteins arising from those transcripts.|
|UniProt||A database of protein sequence and functional information, many of which are derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from the research literature.|
|RCSB PDB||A repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids. The data are typically obtained by X-ray crystallography or NMR spectroscopy.|
|PubMed||References in Guide to Pharmacology are directly linked to citations in PubMed using PubMed IDs.|
|ChEMBL||An online resource of bioactive drug-like small molecule structure-activity data, including 2-D structures, calculated properties and curated bioactivities from medicinal chemistry literature. Guide to Pharmacology links to ChEMBL ligands while IUPHAR-DB links to data organised by target and by ligand.|
|PharmGKB||An integrated resource providing information on how variation in human genetics leads to variation in response to drugs.|
|BindingDB||A public, web-accessible database of measured binding affinities, focusing chiefly on the interactions of protein considered to be drug-targets with small, drug-like molecules.|
|PubChem||A database of chemical molecules and their activities against biological assays.|
|DrugBank||A bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, pathway) information.|
|HMDB||A database of small molecule metabolites found in the human body linked to chemical, clinical and molecular biology/biochemistry data.|
|ChemSpider||A chemical structure database providing fast access to over 25 million structures, properties and associated information. It is considered one of the primary chemistry internet portals and its mission includes improving the quality of public chemistry data sources through automated and crowd-sourced curation with expert review.|
|ChEBI||A database and ontology of molecular entities focused on 'small' chemical compounds. These molecular entities are either products of nature or synthetic products used to intervene in the processes of living organisms. Molecules directly encoded by the genome, such as nucleic acids, proteins and peptides derived from proteins by proteolytic cleavage, are not as a rule included in ChEBI.|
|iPHACE||An integrative web-based tool to navigate in the pharmacological space defined by small molecule drugs contained in the IUPHAR-DB, with additional interactions present in PDSP. Extending beyond traditional querying and filtering tools, iPHACE offers a means to extract knowledge from the target profile of drugs as well as from the drug profile of protein targets.|
|NURSA||The Nuclear Receptor Signaling Atlas is a resource for validated information about nuclear receptor signalling, structure, function and role in disease.|
|Nature Lipidomics Gateway||Information, tools and resources for researchers interested in lipid biology.|
|IUBMB Enzyme Nomenclature||The International Union of Biochemistry and Molecular Biology enzyme resource providing details of accepted nomenclature, systematic names, other names, and reaction information.|
|BRENDA||A resource that comprises molecular and biochemical information on enzymes that have been classified by the IUBMB. Every classified enzyme is characterized with respect to its catalysed biochemical reaction.|
|ZINC||A database containing commercially available compounds for structure-based virtual screening.|
|Wikipedia||Although not always authoritative, it often provides lay, easily-digestible information on drugs and drug targets.|
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