Background

For more information on the Guide to PHARMACOLOGY (abbreviated as GtoPdb) see the About page and the FAQ. The Guide to PHARMACOLOGY is based on information previously available separately in the International Union of Basic and Clinical Pharmacology Database (IUPHAR-DB) and the Guide to Receptors and Channels (GRAC). This help page describes the terms and symbols used in the database and the search tools available on the website.

Terms and symbols

For further information on the pharmacological terms mentioned see the NC-IUPHAR publication on terms and symbols. Please refer also to the Glossary section of this help page.

Tutorial

A tutorial for using the database and guidance on navigating the website is available to download as a PDF.

A set of protocols for using the website has been published in Curr Protoc Bioinformatics. These are useful "how-to" guides with illustrations for using the various features:

Sharman JL et al. (2018) Accessing Expert‐Curated Pharmacological Data in the IUPHAR/BPS Guide to PHARMACOLOGY. Curr Protoc Bioinformatics. 61: 1.34.1-1.34.46.

Immunopharmaoclogy and Malaria Help

Specific help pages on the IUPHAR Guide to Immunopharmacology portal and data

Specific help pages on the IUPHAR/MMV Guide to Malaria Pharmacology portal and data

Contact us

If you would like to get in touch with any comments, questions, error reports and suggestions please email us.

How to cite

Please refer to this page for details on how to cite the information contained in the Guide to PHARMACOLOGY.

The information in the Guide to PHARMACOLOGY builds upon two previously available resources:

1. IUPHAR-DB (www.iuphar-db.org) was developed from 2003-2014 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. These data constitute the detailed target pages on the GtoPdb site. It relies on contributions by expert pharmacologists who volunteer their time. All contributors are attributed near the bottom of the relevant database pages. A full contributor list can be viewed here.

2. The Guide to Receptors and Channels (GRAC) published in the British Journal of Pharmacology:

SPH Alexander, A Mathie, JA Peters. (2011) Guide to Receptors and Channels (GRAC), 5th edition. Br. J. Pharmacol., 164 (Suppl. s1), 1-324.

The Concise Guide to PHARMACOLOGY replaces GRAC and represents a biennial snap-shot view of the concise family pages from the Guide to PHARMACOLOGY website.

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.

Entry points to the data are either via the database search tools (quick search at the top of every page or 'Advanced Search' tools linked from the menu) or through browsing the target and ligand lists. Targets are organised into protein classes (GPCRs, enzymes, ion channels etc) and then subdivided into families (e.g. Adenosine receptors).

Each family page contains a summary of the main properties and the recommended nomenclature and key ligands for each target, as well as a further reading list. This "concise" view of the information for each family serves as a useful "at-a-glance" introduction to the family and to each target.

For the most important targets links are provided to more detailed pages including a longer introduction to the family and detailed pages for each target. Target pages are modelled on IUPHAR-DB pages, with expert-curated information on the nomenclature, genetic, structural, pharmacological, functional, physiological, and clinical properties.

Links are also provided where relevant to further information and the chemical properties of ligand molecules.

We provide selected data files available for download on this page. These are the most commonly requested file formats. We may be able to provide other formats if you email us. We also provide SQL dump files of the full database. The licenses covering reuse of the data are very generous and permit both commercial and non-commercial use with attribution.

Our REST web services and API are intended to provide programmatic access to the data in JSON (JavaScript Object Notation) format, which is easy to read for both humans and computers. Web services are updated at each database release and any changes in the database structure will be reflected in the JSON output. A full listing and examples for using the web services are provided here.

We also provide slide sets and posters including a generic slide set for public use when producing presentations and teaching materials on the Guide to PHARMACOLOGY. The current version can be accessed here.

A quick search box is provided at the top all the main pages. To search for a target, family or ligand start typing the name in the query box and the search function will start looking for matching entries in the database. If any are found they will be displayed as a drop-down list. Clicking on a matching name takes you straight to its database page. Alternatively, type the whole phrase and press "Search database" to perform a complete database search.

You can restrict your search or perform different types of searches, e.g. by database identifier, literature reference, or chemical structure, using the advanced search tools. These can be accessed from the drop down menu on the main menu bar. Advanced search tools include different search options such as restricting text searches to specific database fields or target types, or performing searches 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.

There is also a Pharmacology Search Tool, which allows users to upload target ID sets to retrieve a list of ligands which modulate those targets.

Target search tools

• Target text search: perform keyword searches of selected database fields.
  1. Type the search term(s) into the text box.
  2. If multiple words are entered they must all be present for a result to be returned.
  3. Select the field(s) from the list that you wish to search.
  4. To select multiple fields hold down CTRL while selecting the fields.
  5. To search the entire database select 'All' at the top of the field list.
  6. You can optionally choose to limit your results by species and target type.
• Search by database identifier: retrieve targets by entering external database identifiers or gene names, e.g. Entrez Gene id or HGNC approved symbol.
  1. Type or copy/paste the identifier(s) into the text box.
  2. Alternatively, upload a file containing a list of IDs by clicking on "Browse".
  3. Multiple IDs can be searched by separating them with spaces, tabs or new lines.
  4. Select the source database from the drop-down list. If the IDs are from different source databases, select 'Unknown' in the list.
  5. Please note that searching on large lists of identifiers may fail, and we advise limiting search to <7,500 identifiers.
• Search for literature references: search for families where a particular literature reference appears.
  1. Type a keyword, article title, author last-name or PubMed Id into the text box.
  2. Select the type of query to perform from the drop-down list.
  3. Multiple PubMed identifiers may be entered separated with spaces.
• Search for targets by sequence: perform a sequence-based search for targets using BLAST.

  The BLAST tool allows you to BLAST a sequence against the targets in the Guide to PHARMACOLOGY database. You may supply either a polypeptide sequence or a nucleotide sequence, which will be automatically translated in all possible frames before querying. You have the option of supplying either FASTA sequences or plain text sequences, and the sequence can be pasted directly into the search box or uploaded from your local file system.

  You can filter the results you get back by species, control the maximum number of hits and number of hits per page, and also specify a maximum E-value (expect value) for your query – the larger this E-value, the more distantly related the sequences it returns will possibly be.

  Once the results are displayed, the aligned sequences will by default be coloured according to residue, but this can be disabled.

Ligand search tools

• Ligand name search: retrieve compounds by matching to their name. Also (optionally) searches in target interaction comment fields (agonists, antagonists etc) for matches.
  1. Type the search term(s) into the text box.
  2. If multiple words are entered they must all be present for a result to be returned.
  3. Check the box to include searches on comment fields or uncheck to exclude.
  
  
• Search by database identifier: retrieve compounds by entering an external database identifier, e.g. PubChem CID or ChEBI id (in this case the number must be prefixed with "CHEBI:").
  1. Type the identifier into the text box.
  2. Select the source database from the drop-down list.
  3. Multiple identifiers can be searched by separating them with spaces. If they are from different source databases, select 'Unknown' in the database list.
  4. Please note that searching on large lists of identifiers may fail, and we advise limiting search to <7,500 identifiers.
  
  
• Search for literature references: search for families where a particular literature reference appears.
  1. Type a keyword, article title, author last-name or PubMed Id into the text box.
  2. Select the type of query to perform from the drop-down list.
  3. Multiple PubMed identifiers may be entered separated with spaces.
• Chemical structure search: search for compounds by chemical structure. Performs substructure, SMARTS, similarity and identity (exact) searches.
  
  

  Substructure

  This search uses the Chemistry Development Kit (CDK) algorithm to match a drawn 2D structure and returns any compounds which contain the query structure.

  SMARTS

  Uses Chemistry Development Kit (CDK) for matching Daylight SMARTS and returns any compounds which match the query.

  Similarity

  Similarity search uses the Tanimoto coefficient to compare the similarity between the query molecule and molecules in the database using Pinpoint generated expanded fingerprints and returning all molecules above a user selected threshold (>70% or 85%).
  Please note: if your similarity search does not return appropriate results please try using the substructure function. (We are currently working on optimising our similarity search.)

  Exact

  Exact match query returns all compounds matching the canonical SMILES, with no regards to the chiral specification. This is attained by Tanimoto comparison of fingerprints and returning all with 100% similarity.

  Usage
  1. Either: enter a SMILES or SMARTS representation of the chemical structure into the text box and press 'Import SMILES/SMARTS' to load the structure into the editor.
  2. Or: draw the chemical structure into the editor. The icon in the top right above the atoms can be used to add other atoms, R groups and SMARTS groups.
  3. Choose the type of search to perform from the drop-down menu on the top right (e.g. similarity - high).
  4. Choose the type of chemical class to search for (recommended type is small molecules but you can also search for peptides with SMILES available).
  5. The returned structures are roughly ordered according to their flexibility/complexity.
  6. On the results page, clicking on a ligand's image or name will take you to its ligand page. Clicking on the 'Use in search' button will load the ligand into the editor so it can be modified if required and used in a further search.
  Notes
  1. Currently the search function does not consider chiral specification of matched compounds. This is to ensure that all relevant results will be returned. Please ensure that your input structure does not include chiral or isotopic specification, otherwise exact match, substructure and SMARTS searches may miss relevant structures.
  2. Exact match, substructure and SMARTS searches are currently not able to recognise alternative tautomers that may be in the database. Please use similarity searching if you suspect this could be occurring.

Pharmacology search tool

• Pharmacology search by target: upload a set of target IDs (e.g. UniProtKB accessions, Ensembl Gene IDs) to retrieve a list of ligands known to modulate them.
  1. Type or copy/paste the identifier(s) into the text box.
  2. Alternatively, upload a file containing a list of IDs by clicking on "Browse".
  3. Multiple IDs can be searched by separating them with spaces, tabs or new lines.
  4. Please note that searching on large lists of identifiers may fail, and we advise limiting search to <7,500 identifiers.
  5. Select the source database from the drop-down list. If the IDs are from different source databases, select 'Unknown' in the list.
  6. You may choose to limit the interaction data to a particular species, and also select the number of interactions returned (the default returns the top 5 interactions, ordered by decreasing affinity).
  7. You can choose to include a ChEMBL database search as well, which may find additional ligands. (The ChEMBL data has been filtered and selected according to the rules outlined below)
  8. On the results page the targets are ordered by how many interactions they have that match the search criteria.
  9. 10 results are shown per page. Scroll down to the bottom to move between pages.
  10. If ChEMBL data were included, these are shown in a separate table beneath the GtoPdb ligands matching each target entry. The ChEMBL curated activity values are shown, along with a calculated pChEMBL (-log to base 10) value, where available.
  11. A more detailed table of results (including ligand structures and affinity values) is available to download as a CSV file by clicking the "Download" button at the top of the page.

Downloading results

The results of many of the searches described above can be downloaded as a CSV file containing additional information about the matched entities. This can be acheived by clicking on the "Download" button at the top right of the results page. Additional data for targets includes gene IDs and symbols, and for ligands PubChem IDs and chemical structures, as well as their GtoPdb URLs.

For all targets; additional information relevant to specific target types is listed below this section.

Overview - Provides a brief introduction to the target family. For targets where a more comprehensive introduction may be available, a link is provided to the relevant page.

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.

Other names - Details a list of alternative names that exist in the literature, but are not the recommended nomenclature.

More detailed page - Links to the more detailed target page.

Subunits - Lists the subunits that together make up the homomeric or heteromeric protein.

Genes, UniProt 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 and the UniProt protein knowledgebase. Further database links can be accessed via the more detailed target pages. For descriptions of databases linked to see the Database Links table.

Rank order of potency (certain targets) - Details the order of potency of the activity of a series of ligands at a particular target.

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.

Comments - Includes additional comments and information about the target family and data presented in the tables.

Further reading - A selection of background literature on the target family.

References - An alphabetical list of references cited in the target family pages.

N.B. The concise family pages focus on the properties of human targets and data referring to other species are indicated accordingly.

Nomenclature - The recommended nomenclature for a structurally and operationally distinct target in a given family. Where relevant this is the NC-IUPHAR recommended nomenclature published 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. See the relevant target section below for further information.

Colour codes - Each target page and introduction are given a colour code to indicate the status of their annotation:

 Annotated and expert reviewed

Data have been annotated and reviewed by an expert. Please contact us if you can help with updates.

 Annotated and awaiting review

Available data have been entered by experts or curators but are yet to be reviewed by independent experts. Please contact us if you can help with reviewing.

 Awaiting annotation/under development

These pages are awaiting annotation. A minimum amount of data are displayed about receptors, e.g. nomenclature and database links. Whilst some pages are under development, others still need volunteers so please contact us if you can help with annotation.

Gene and Protein Information - For human, mouse and rat targets the following data are displayed:

Column	Definition
Transmembrane domains (TM)	The number of times the polypeptide passes through the cell membrane.
P loops	(Some ion channels only) The number of pore loops in the protein.
Amino acids (AA)	The number of amino acids which make up the protein.
Chromosomal location	The genetic location of the encoding gene.
Gene symbol	The official symbol given to the gene that codes for the target which, if highlighted in blue, links to either the HGNC, MGI or RGD databases.
Gene name	The full name of the gene that codes for the target.
Reference	A reference to the first paper(s) describing the cloning of the target.

Previous and Unofficial Names - Alternative names that exist in the literature or other databases, but are not the current recommended nomenclature. Also includes any previous gene symbols or names used for human, mouse or rat genes.

Database Links - Links are provided to other relevant resources, including genomic databases (e.g. Ensembl, Entrez Gene), protein databases (e.g. RefSeq, Uniprot) and others such as ChEMBL (MedChem literature data on drug-like molecules and their targets) and DrugBank (data on approved drugs and the proteins they interact with). For a full list and descriptions see the Database Links table.

Selected 3D Structures - Highest resolution structures were selected and an attempt was made to include for each target the unliganded, agonist, and antagonist bound structures where available. Links are provided to associate ligands with RCSB PDB ligand pages where possible.

Natural/Endogenous Ligand(s) - The principal endogenous or natural ligand(s) for the target.

Ligands - Ligands are arranged in tables according to their action at the target.
The column headings or icons in the ligand table are described below:

Icon/Table heading	Definition
	Indicates that a ligand is either a small organic molecule (synthetic or naturally occurring) or a natural product (or derivative).
	Indicates that a ligand is a peptide (synthetic or naturally occurring) or antibody.
	Indicates that the ligand is or has in the past been approved for human clinical use by a regulatory agency.
	Indicates that the target may be considered the primary target of the compound. In some cases, e.g. dual inhibitors, a compound may have more than one primary target.
	Indicates that there are data available for the ligand binding to other targets in the database. Clicking on this icon displays the list of targets and the ligand's potency at each target.
	Indicates that the ligand is endogenous in the species of the target under test.
	Indicates that the ligand is chemically labelled such as with an unstable isotope, fluorescent tag or small chemical entity.
	Indicates that the ligand is labelled with a radioactive isotope.
	Indicates that the ligand has an entry in the Protein Data Bank (PDB).
	Indicates that the ligand has been tagged in the database as being relevant to immunopharmacology.
	Indicates that the ligand has been tagged in the database as an antimalarial.
	Indicates that there are Ligand Activity Charts available for this ligand. These provide a visualisation of activity data, across species, from GtoPdb and ChEMBL (where available).
Hs, Mm, Rn etc	Indicates the species of the target and NOT the species of the ligand. '?' indicates that the species was not given in the original publication. Selectivity tables are not shown when the species is unknown. Mouse-over the short name to see the longer species name.
Ligand	The name of the ligand, which can be clicked on to open a ligand page. Ligand pages include database links, alternative names, data on affinity for other targets, structural information and links to similar ligands, where available.
Action	This indicates how the ligand binds to the target (see the terms and symbols document for a definition of the terms).
Value	A measure of how strongly the ligand binds to the target. In cases where no binding data are available functional data may be used.
Parameter	The parameter used to measure the ligand's binding to the target (see the terms and symbols document for a definition of the terms).
Concentration range	Where affinity data are not available, the concentration range of ligand used for the study is displayed (in M).
Holding voltage	The voltage at which the displayed affinity was determined (in mV). 'Physiological' indicates that the experiment was performed in intact cells where voltage could not be determined.

The ligands can be sorted in alphabetical order or by action, affinity, unit, concentration range or holding voltage by clicking on the column header.

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 ligands with activities below a particular concentration will be displayed on the target page and a link is given to the full set of data for the target. Where the screen tested multiple variants of the target the data for the variants are displayed in separate tables. Similarly, on ligand pages the screening data are displayed in separate tables, with targets ordered by activity level.

Functional Assay - Details of pharmacological test systems (whole tissues or isolated cells) in which a response can be firmly attributed to the function of a defined receptor type.

Tissue Distribution - Central and peripheral distribution of the receptor (and the identifying techniques).

Expression Datasets - Graphical displays of selected high-throughput expression datasets.

Physiological Functions - The physiological response mediated by the receptor if established in whole tissue, preferably in vivo.

Physiological Consequences of Altering Gene Expression - Important physiological differences observed as a result of modifying expression levels (e.g. knockouts).

GPCRDB Experimental Mutation Data - Data on experimentally generated mutations from literature are provided for GPCRs by GPCRDB. GPCRDB is working with a consortium to collate data on GPCR mutants and is inviting submissions. Thus, the mutation data displayed here will update automatically whenever GPCRDB release new data.

Phenotypes, Alleles and Disease Models - Additional data on "spontaneous, induced and genetically-engineered mutations and their strain-specific phenotypes" from Mouse Genome Informatics.

Clinically-Relevant Mutations and Pathophysiology - Details of the pathophysiologies in which the receptor is involved, including, where available, the ligands at the receptor which are of therapeutic use. Details are provided of individual mutations that lead to the pathophysiology, in terms of the change in the amino acid sequence.

Gene Expression and Pathophysiology - The pathophysiology that arises from abnormal gene expression.

Biologically Important Receptor Variants - Details of polymorphisms and post-transcriptional modifications (e.g. splice variation) that influence function. Where possible links to the protein and nucleotide sequences are provided.

N.B. additional species are sometimes used where data for human, rat and mouse are unavailable, the most common are: Bt (bovine), Oc (rabbit), Cp (guinea pig), Clf (dog).

Concise pages

Nomenclature - The NC-IUPHAR recommended nomenclature for a structurally and operationally distinct receptor or subunit in a given family. NC-IUPHAR publishes its recommended nomenclature in Pharmacological Reviews. In cases where no publication yet exists this is the preliminary recommendation from NC-IUPHAR.

Primary/Principal Transduction - The preferred principle receptor signalling pathway or mechanism, where established. This is the mechanism that used as the principal signalling activity in order to regulate established physiological function.

More detailed pages

Secondary Transduction Mechanisms - The secondary receptor signalling pathways or mechanisms, where established.

Ligands - Ligands are categorised as agonists, antagonists or allosteric regulators.

For voltage-gated (VGIC), ligand-gated (LGIC) and other types of ion channels

Concise pages

Nomenclature - The NC-IUPHAR recommended nomenclature for a structurally and operationally distinct receptor or subunit in a given family. NC-IUPHAR publishes its recommended nomenclature in Pharmacological Reviews. In cases where no publication yet exists this is the preliminary recommendation from NC-IUPHAR.

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.

More detailed pages

Associated Proteins - Proteins that interact directly with the receptor either as heteromeric pore-forming subunits, auxiliary subunits or associated proteins.

Ion Selectivity and Conductance - This table displays relative or absolute conductance data for the receptor on a 'per species' basis.

Voltage Dependence - (VGICs only) This table displays the voltages of activation, inactivation and deactivation and the relevant time constants, where available.

Ligands - For LGICs, ligands are categorised as agonists, antagonists, channel blockers or allosteric regulators. For VGICs, ligands are categorised as activators, channel blockers or gating inhibitors, according to the following definitions:

Activators

Ligands that activate ion channels by binding directly to them, including ligands that cause a change in the voltage dependence of channel gating that favors activation.

Gating inhibitors

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.

Channel blockers

Ligands that block ion movement through the pore of ion channels.

Concise pages

Nomenclature - Typically the most commonly used name for the receptor.

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]

More detailed pages

Ligands - Compounds that bind reversibly to NRs into the C-terminal ligand binding pocket (LBP).

Agonists

Ligands that induce an active conformation of the receptor.

Antagonists

Ligands that produce a conformation and an action of the receptor distinct from that produced by an agonist.

Inverse agonists

Ligands that can promote corepressor recruitment.

Partial agonists

Agonists that in a given tissue, under specific conditions, cannot elicit as optimal 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.

Unliganded receptor - Considered preferable compared with apo-receptor.

DNA Binding - Hormone response elements (HRE) are DNA recognition sites which include inverted repeat DNA half sites and direct repeats (e.g. DR1-DR5) for homodimeric and heterodimeric receptors respectively.

Co-binding Partners - Proteins which specifically interact with and induce a functional effect with NRs.

Co-regulators - Macromolecules that associate with NRs to modulate their transcriptional activity; divisible into coregulators that promote positive activity (coactivators) and those that promote negative activity (corepressors).

Main Target Genes - Genes regulated directly by the actions of NRs.

Transactivation - Activation of transcription by the binding of a transcription factor (and coregulators) to a DNA regulatory sequence.

Isoforms - Products of the same gene produced by alternative splicing, alternative promoter usage, alternative translational initiation; does not consider post-translational modifications; examples: RARα1 and RARα2.

Terms and definitions were adapted from the IUPHAR Compendium.

Concise pages

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), is the HGNC approved name or is based on nomenclature in common use in the literature.

Abbreviated Name - An abbreviated name commonly used in the literature.

Systematic Name - A systematic name used by HGNC or inthe literature.

Endogenous Ligands - Ligands originating from within the studied organism shown to have activity at the receptor.

Adaptor Proteins - Cytoplasmic-based proteins containing protein-binding modules involved in catalytic receptor signalling.

E.C. Number - See below description for enzymes.

Concise pages

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), is the HGNC approved name or is based on nomenclature in common use in the literature.

Common Abbreviation - Typically the most commonly used abbreviation for the enzyme name as used in the literature; not necessarily the preferred abbreviation.

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.

Product - The substance arising from conversion of a substrate by an enzyme.

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.

Activator/Endogenous Activator - A substance that increases enzyme activity after binding to the enzyme.

Cofactor - A chemical substance that binds to the enzyme and is required for its activity. Cofactors are non-peptides, and may be organic or inorganic compounds.

More detailed pages

K_m - The Michaelis constant (Km) defines the concentration of substrate when the reaction rate is half of V_max.

V_max - The maximal rate of reaction, or maximal velocity reached by the system when under conditions of maximum (saturating) concentrations of substrate.

Nomenclature - Typically the most commonly used name for the transporter.

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]

Common Abbreviations - Commonly used abbreviations of the transporter that exist in the literature.

Other Names - Alternative names that exist in the literature, but that are not the recommended nomenclature.

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.

Functional Characteristics - Provides details of the conductance, voltage- and time-dependence properties of transporters.

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.

Synonyms - Alternative names that exist in the literature, which may include systematic names.

Icon/Table heading	Definition
	Indicates that a ligand is either a small organic molecule (synthetic or naturally occurring) or a natural product (or derivative).
	Indicates that a ligand is a peptide (synthetic or naturally occurring) or antibody.
	Indicates that the ligand is or has in the past been approved for human clinical use by a regulatory agency.
	Indicates that the ligand is chemically labelled such as with an unstable isotope, fluorescent tag or small chemical entity.
	Indicates that the ligand is labelled with a radioactive isotope.
	Indicates that the ligand has an entry in the Protein Data Bank (PDB).
	Indicates that the ligand has been tagged in the database as being relevant to immunopharmacology.
	Indicates that the ligand has been tagged in the database as an antimalarial.
	Indicates that there are Ligand Activity Charts available for this ligand. These provide a visualisation of activity data, across species, from GtoPdb and ChEMBL (where available).

Approved drug - Indicates pharmacologicaly active substances, specified by their INNs, that have been approved for clinical use by a regulatory agency, typically the FDA, EMA or in Japan. This classification persists regardless of whether the drug may later have been withdrawn or discontinued. (N.B. in some cases the information on approval status was obtained indirectly via databases such as Drugbank.)

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.

Ligand Activity Charts

This tool provides charts with box plots summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

Filtering ChEMBL data - activity data are extracted from ChEMBL 34* according to the following rules:

1. The target must have a type of 'SINGLE PROTEIN', 'PROTEIN COMPLEX', or 'PROTEIN COMPLEX GROUP'
2. Affinity types are combined and normalised as follows:
   K_d = Dissociation constant, Kd, K app, K Bind, K calc, Kd', KD app, KD', Kd(app), KD50, Kdiss, Relative Kd, Binding constant, K aff, K diss, KD/Ki
   pK_d = -Log Kdiss, -Log KD50, pKd, pKD, logKd, -Log Kd, Log Kd, -Log KD, Log KD
   K_i = Adjusted Ki, Ki, ki, Ki app (inact), Ki app, Ki(app), Ki_app, Ki', Ki'', KI', K'i, Kiact, Ki high, Ki low, KiH, KiL, Kii, KII, Kic, Ki.c, Ki comp, Ki' uncomp
   pK_i = pKi(app), pKi, -Log K0.5, Log Ki, logKi, -Log Ki, pKiH, pKiL
   IC₅₀ = IC50 app, IC50, IC50 max, I50, Mean IC50, IC50H, IC50L
   pIC₅₀ = pIC50, pIC50(app), -Log I50, logIC50, log IC50, Log IC50, -Log IC50, pI50, pIC50(calc)
   EC₅₀ = EC50
   pEC₅₀ = pEC50 diss, pEC50, -Log EC50, Log EC50, logEC50
   A₂ = A2
   pA₂ = pA2, pA2(app), pA2 app, pA2/pKB
3. Raw data (e.g. K_is are converted into their negative log to base 10 values (e.g. pK_is)
4. Activities deemed by ChEMBL curators to be "outside typical range" are ignored (to prevent skew)
5. Only binding ('B') and functional ('F') assays are included (no large-scale screening data)

Tables of activity data - Below the charts are tables listing all the data points included in the dataset. These are divided up by target and species and the source database is indicated, with assay description if available. The GtoPdb standard data type (pK_d, pK_i, pIC₅₀, pEC₅₀ or pA₂) and value are given alongside the source database's original value and type (which may be the original data reported in the publication or that has been further curated by the ChEMBL team using one of the activity types given above). We recommend always checking the data in the original reference, which is provided along with a PubMed link.

*For more information about ChEMBL see their publication:

Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]

---

2D Structure - An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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:

Number of Hydrogen Bond Acceptors

Number of Hydrogen Bond Donors

Number of Rotatable Bonds

Molecular Weight

Topological polar surface area

Polar surface area (PSA) is defined as the surface sum over all polar atoms (usually oxygen and nitrogen), including also attached hydrogens. Topological polar surface area is a useful parameter (molecular descriptor) employed for optimising cell permeability by medicinal chemists. It is generated by a computation of functional group contributions. For details on the methodology used see
Ertl, P., Rohde, B., and Selzer, P. (2000) Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties. J. Med. Chem. 43, 3714–3717.

XLogP

Log of partition coefficient (LogP) is the logarithm of the ratio of concentrations of un-ionized compound between two solutions (octanol and water). The prediction of LogP is based on the atom-type method called XLogP as implemented in KNIME. For details of the methodology see
Wang, R., Fu, Y., and Lai, L. (1997) A New Atom-Additive Method for Calculating Partition Coefficients. Journal of Chemical Information and Computer Sciences. 37, 615-621.

No. Lipinski's rules broken

Lipinski's Rule of Five is a rule of thumb to evaluate ‘druglikeness’, or determine if a chemical compound with a certain pharmacological or biological activity has properties that would make it a likely orally active drug in humans. For further details see
Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J. (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev. 23, 3–25.

SMILES / InChI / InChIKey - Structure Downloads - Various representations of the ligand 2D molecular structure, generated using Open Babel. These are:

SMILES (Simplified Molecular Input Line Entry Specification)

A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey

InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

WHO - Indicates ligands which are included in the World Health Organization (WHO) Model List of Essential Medicines (21st list, 2019).

Withdrawn drug - No longer approved for its original clinical use, as notified by the FDA, typically as a consequence of safety or side effect issues.

Discontinued drug - No longer marketed for routine clinical use but not withdrawn because of negative effects. Typically these have been superceeded by newer, more effective drugs.

Prodrug - Substance covalently changed into an active drug after administration, via active metabolism or passive hydrolysis. Prodrugs can be inactive. Both approved prodrug and drug will have different INNs while development prodrugs and drugs may have different code names. Prodrugs are linked to drug database pages and vice versa.

DrugBank drug categories are also provided where possible.

IUPAC name - A systematic chemical name generated according to IUPAC rules using the NCI/CADD Chemical Identifier Resolver

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, 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.

This section includes a new option to display the results for an InChIKey search in Google, the utility of which has recently been described (Southan 2013). While the entire Key is used for exact-match searches of ChemSpider, the Google search uses just the inner "layer" of 14 characters approximating to the basic molecular connectivity. It will thus retrieve all related entries with isomeric differences encoded in the outer layer of the key. The results, typically returned in less that 0.5 seconds with very high specificity, are collated from over 50 million InChIKeys cached by Google from a comprehensive range of databases and web resources. See reference: Southan C (2013). InChI in the wild: an assessment of InChIKey searching in Google. J Cheminform. 5, 10. [PMID:23399051]

Biological Activity - Tables of selectivity at targets in the database. Data are separated by target type (GPCR, ion channel, NHR, enzyme, catalytic receptor, transporter, other protein target) and by species.

Natural/Endogenous Targets - Targets where the ligand acts as the principal endogenous or natural ligand.

Enzymes/Transporters - Where the chemical is part of an enzyme reaction annotated in the database or is known to be a substrate for a transporter protein in the database, these are listed.

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.

Summary of Clinical Use - Overview of the principal uses of approved drugs in the clinic. Lists the condition(s) for which the drug is used, or has been used, to treat. In the case of drugs with multiple targets, this field may indicate which of these targets is the main therapeutic target.

Mechanism Of Action and Pharmacodynamic Effects - Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body and examines the mechanisms of drug action, including the relationship between drug concentration and effect.

Pharmacokinetics

Absorption/Distribution

Consideration of the factors which affect how much an administered drug gets into the bloodstream and how much is available at its effector (i.e. bioavailability at the drug target). For orally administered drugs, compound solubility, gastric emptying time, intestinal transit time, chemical instability, and ability to cross gut mucous membranes all need to be considered. If these obstacles are insurmountable another route of administration must be found.

Metabolism

The mechanisms by which the body breaks down drugs. For most small-molecule drugs metabolism is performed by the cytochrome P450 redox enzymes in the liver.

Elimination

The routes via which the body eliminates drugs and their metabolites.

Population pharmacokinetics

The effects of the drug in specific groups, based on age, gender, race or weight or in populations with pre-existing conditions, or otherwise requiring special consideration (such as paediatric geriatric populations).

Organ function impairment

Dosing considerations in populations with specific organ impairment, especially in patients with renal and hepatic insufficiency as these conditions may disturb metabolism and elimination and thereby affect the total bioavailability of the drug. In such groups dose adjustments may be necessary.

ADME links - links to detailed information on ADME properties.

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. Where curated, peptide HELM (Hierarchical Editing Language for Macromolecules) notation is also shown.

Similar Ligands (small molecules) - Similar ligand sets were generated using a clustering algorithm implemented in Pipeline Pilot (Accelrys, San Diego, CA, USA).

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.

The Guide to PHARMACOLOGY ligand list provides a directory of ligands described in the database, divided into subsets according to chemical category. A list of approved drugs and a list of ligands labelled with a chemical group, such as a radioactive isotope, are also provided. Ligands are sorted alphabetically as far as possible.

Associated with - Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

Synonyms - Synonyms for the disease.

Description - A description/definition of the disease.

Database Links - External links to the same disease at the Disease Ontology, OMIM or Orphanet sites - where data are available.

Targets

Each section gives details about the pathophysiology, mutation and immunopharmacology data for the target in relation to the disease. Details of the pathophysiologies in which the target is involved, including, where available, the ligands at the target which are of therapeutic use. If there are details of individual mutations that lead to the pathophysiology, these are indicted, with links back to the relevant section of the detailed target page for further details.

Immuno ligand interaction - Where available a table of immuno-relevant ligands is shown, that also have an association to the disease. The ligands all have interaction data with the target. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

Ligands

A table of all ligands curated in GtoImmuPdb as being associated with the disease.

Approved - If the ligand is an approved drug this is indicated, along with approval bodies.

Clinical comments (Clinical Use) - The clinical use comments are general clinical comments relating to the ligand and may not necessarily be specific to the disease in question.

Clinical comments (Immuno Disease Comments) - These are curatorial comments specifically added as part of GtoImmuPdb. They gives more information on the association between the ligand and disease in the context of immunopharmacology.

The Guide to PHARMACOLOGY disease list provides a directory of diseases described in the database. Currently two lists are available:

All Diseases - all the diseases with curated information in the GtoPdb
Immuno Disease - diseases of immunological relevance. These are diseases that are relevant to immunology or are associated to targets and ligands of immunological relevance.

Diseases are sorted alphabetically as far as possible.