Poster presented at the Elixir All-Hands Meeting in Lisbon, June 2019. Gives a broad summary of Guide to Pharmacology activities in the last year. Emphasising new tools and our extension into malaria pharmacology.
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) is an expert-driven, open database of pharmacological targets and the substances that act on them. It contains information on over 1,800 drug targets and 1,100 related proteins. The database is curated by 500 experts and provides detailed pharmacological data as well as overviews of key properties and ligands. Specialized extensions of GtoPdb include guides to immunopharmacology and malaria pharmacology that connect their fields to drug discovery. The database is continuously updated with new targets, ligands, features and access methods.
1) Researchers have created a new online resource called the IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb) to curate information on antimalarial compounds and their molecular targets in Plasmodium.
2) The database currently contains 25 Plasmodium molecular targets and 57 antimalarial ligands that were manually curated from scientific literature.
3) A new customized online portal provides open access to the antimalarial data and allows browsing by parasite lifecycle stage, target species, and other features to help malaria research.
The document summarizes recent updates to the IUPHAR/BPS Guide to PHARMACOLOGY database. It describes new features including expanded target coverage with over 1,700 drug targets and 1,100 related proteins. A new Pharmacology Search Tool allows users to upload protein lists and find associated ligands. The database also now connects immunopharmacology by associating targets with immune processes, cell types, and diseases. Additionally, the guide describes collaborations to include antimalarial compound data and develop an IUPHAR/MMV Guide to Malaria Pharmacology.
The IUPHAR/BPS Guide to PHARAMCOLOGY in 2018: new features and updatesGuide to PHARMACOLOGY
2018 update poster for the IUPHAR/BPS Guide to PHARMACOLOGY. Giving details of new features and updates. To be presented at Pharmacology Futures, Edinburgh, May 2018; ELIXIR-All Hands, Berlin, June 2018 and World Congress of Pharmacology, Kyoto, Japan, July 2018
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) is an open, expert-driven database that contains information on over 1,700 pharmacological targets and the substances that act on them. The database provides overviews and detailed information on targets that is manually curated from literature and reviewed by experts. It aims to cover human drug targets and potential future therapeutic targets. New features of the database include search tools to find targets and ligands, information on diseases associated with targets and ligands, organization of ligand families, and comparison of ligand activity across species. The database content is available to download in various formats and its interoperability has been increased through developing an RDF version and submitting data to other sources
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) is an expert-driven, open database of pharmacological targets and the substances that act on them. It contains information on over 1,800 drug targets and 1,100 related proteins. The database is curated by 500 experts and provides detailed pharmacological data as well as overviews of key properties and ligands. Specialized extensions of GtoPdb include guides to immunopharmacology and malaria pharmacology that connect their fields to drug discovery. The database is continuously updated with new targets, ligands, features and access methods.
1) Researchers have created a new online resource called the IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb) to curate information on antimalarial compounds and their molecular targets in Plasmodium.
2) The database currently contains 25 Plasmodium molecular targets and 57 antimalarial ligands that were manually curated from scientific literature.
3) A new customized online portal provides open access to the antimalarial data and allows browsing by parasite lifecycle stage, target species, and other features to help malaria research.
The document summarizes recent updates to the IUPHAR/BPS Guide to PHARMACOLOGY database. It describes new features including expanded target coverage with over 1,700 drug targets and 1,100 related proteins. A new Pharmacology Search Tool allows users to upload protein lists and find associated ligands. The database also now connects immunopharmacology by associating targets with immune processes, cell types, and diseases. Additionally, the guide describes collaborations to include antimalarial compound data and develop an IUPHAR/MMV Guide to Malaria Pharmacology.
The IUPHAR/BPS Guide to PHARAMCOLOGY in 2018: new features and updatesGuide to PHARMACOLOGY
2018 update poster for the IUPHAR/BPS Guide to PHARMACOLOGY. Giving details of new features and updates. To be presented at Pharmacology Futures, Edinburgh, May 2018; ELIXIR-All Hands, Berlin, June 2018 and World Congress of Pharmacology, Kyoto, Japan, July 2018
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) is an open, expert-driven database that contains information on over 1,700 pharmacological targets and the substances that act on them. The database provides overviews and detailed information on targets that is manually curated from literature and reviewed by experts. It aims to cover human drug targets and potential future therapeutic targets. New features of the database include search tools to find targets and ligands, information on diseases associated with targets and ligands, organization of ligand families, and comparison of ligand activity across species. The database content is available to download in various formats and its interoperability has been increased through developing an RDF version and submitting data to other sources
Poster on GtoImmuPdb presented at European Congress of Immunology (Amsterdam, Sep 2018). Overview of the main data types and features included in this extension to the IUPHAR/BPS Guide to PHARMACOLOGY
Presentation by Dr. Elena Faccenda on the IUPHAR/BPS Guide to Immunopharmacology at the 39° Congresso Nazionale della Società Italiana di Farmacologia in Florence, Nov 2019
This document discusses the IUPHAR/BPS Guide to Pharmacology database and related resources. It provides open access information on pharmacological targets and the substances that act on them. It includes over 1,700 human drug targets, 9,700 ligands including 1,300 approved drugs. Related databases include the Guide to Immunopharmacology and Guide to Malaria Pharmacology. The databases are regularly updated and include links to other resources to enable interoperability.
This document describes updates to the Guide to PHARMACOLOGY (GtoPdb) database in 2017, including new features such as:
1) Organization of drug targets into families and subclasses for easier browsing, and organization of ligands into related families and groups.
2) Ability to visualize ligand binding affinities across species through activity graphs.
3) SynPHARM database for finding ligand binding sequences that can be engineered into synthetic proteins.
4) Expanded content with over 1,700 drug targets, 9,000 ligands, and options to search or download data in various formats.
Neglected infectious diseases such as tuberculosis (TB) and malaria kill millions of people annually and the oral drugs used are subject to resistance requiring the urgent development of new therapeutics. Several groups, including pharmaceutical companies, have made large sets of antimalarial screening hit compounds and the associated bioassay data available for the community to learn from and potentially optimize. We have examined both intrinsic and predicted molecular properties across these datasets and compared them with large libraries of compounds screened against Mycobacterium tuberculosis in order to identify any obvious patterns, trends or relationships. One set of antimalarial hits provided by GlaxoSmithKline appears less optimal for lead optimization compared with two other sets of screening hits we examined. Active compounds against both diseases were identified to have larger molecular weight ([similar]350–400) and logP values of [similar]4.0, values that are, in general, distinct from the less active compounds. The antimalarial hits were also filtered with computational rules to identify potentially undesirable substructures. We were surprised that approximately 75–85% of these compounds failed one of the sets of filters that we applied during this work. The level of filter failure was much higher than for FDA approved drugs or a subset of antimalarial drugs. Both antimalarial and antituberculosis drug discovery should likely use simple available approaches to ensure that the hits derived from large scale screening are worth optimizing and do not clearly represent reactive compounds with a higher probability of toxicity in vivo.
PubChem for drug discovery and chemical biologyChris Southan
This document provides an overview of the PubChem database for academic drug discovery and chemical biology. It describes PubChem's large content of over 97 million compounds and 3.4 million with bioactivity results. It highlights drug-related resources in PubChem like ChEMBL and the Guide to Pharmacology. It also demonstrates several use cases, including searching structures extracted from patents, linking between papers and chemistry, and getting probes mapped into PubChem.
Antimalarial drug dscovery data disclosureChris Southan
Dr. Christopher Southan presented on comparing open and closed antimalarial drug discovery approaches. He examined 32 recent antimalarial compounds and found major data connectivity issues, such as leads not being findable by code name or having publications not citing patents. In contrast, the open source Sydney University Malaria Project surfaces structures and shares data in near real-time through open lab books and crowdsourcing. Dr. Southan analyzed their collection of 411 molecules and found 250 matched in PubChem quickly. Open approaches can accelerate discovery by years by openly sharing data.
Updated poster following beta v3 release. In preparation for Pharmacology Futures, Edinburgh Immunology Symposium and Word Congress of Pharmacology (Kyoto)
This study aimed to identify existing drug therapies that could potentially be repurposed to treat gastric cancer. Differentially expressed genes from microarray analyses of gastric cancer tissue samples were submitted to the Connectivity Map database to identify candidate drugs that could reverse disease signatures. Vorinostat and trichostatin A, both histone deacetylase inhibitors, were predicted as potential therapies based on their expression profiles opposing those of gastric cancer tumors. Future work will integrate biological pathway knowledge to link predicted drugs to relevant pathways.
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...Chris Southan
The document summarizes the IUPHAR/BPS Guide to Pharmacology (GtoPdb) database, which maps relationships between chemistry, data, and protein targets. It has evolved from earlier databases to now include over 1500 human protein targets linked to ligand data. Challenges include resolving relationships across different target hierarchies and filling data gaps. Future plans include expanding the database and linking it to immunopharmacology data through a new Guide to Immunopharmacology portal.
Poster titled "The imperative of small, high quality data for underpinning big data: the IUPHAR/BPS Guide to PHARMACOLOGY". Presented by Dr. Christopher Southan, at the British Society of Pharmacology, Institute for Translational Medicine & Therapeutics (ITMAT) Meeting, Edinburgh, March 2017, ‘Big Data & the Development of New Medicines’.
This document discusses databases that define the druggable proteome - the portion of the human proteome that can bind small molecules with sufficient affinity for modulating protein function. Four databases - ChEMBL, BindingDB, DrugBank, and IUPHAR/BPS Guide to PHARMACOLOGY - provide evidence-supported links between human proteins and drug targets. Their intersection identifies ~490 proteins (13% of the union of targets) as the most precisely defined druggable proteome. Comparative analyses examine distributions of targets by function and other attributes. Initiatives aim to expand knowledge of currently unannotated but potentially druggable protein families to broaden therapeutic opportunities.
Guide to PHARMACOLOGY: a web-Based Compendium for Research and EducationChris Southan
This document summarizes a presentation about the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) database. The following key points are made:
- GtoPdb is an online resource containing information on over 8,000 ligands and their interactions with around 1,500 human protein targets. It has been used widely by researchers and educators since 2009.
- The database contains detailed information on drug targets like GPCRs, ion channels, and enzymes. It also provides data on ligands, drugs, interactions between ligands and targets, and related clinical information.
- Users can browse targets and ligands or search the database. Detailed target pages contain pharmacology data, mechanisms, and links
Curatorial data wrangling for the Guide to PHARMACOLGY Chris Southan
This document discusses the challenges and experiences of curating quantitative target-ligand interaction data for the Guide to PHARMACOLOGY database from the primary literature. Standardizing entities such as proteins, ligands, and measurement units across different data sources can be difficult due to inconsistencies in naming, identifiers, and reporting of values. Initiatives by publishers to have authors mark up key entities in manuscripts may help curators but will not solve all compatibility issues. The curation process also requires judgment calls on issues like resolving conflicts between data sources and determining whether reported data can be structurally defined.
The IUPHAR/MMV Guide to Malaria Pharmacology Chris Southan
This document summarizes the creation of the IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb) database by the authors. It captures antimalarial compounds, targets, and their relationships by curating data from publications. The database has adapted the Guide to Pharmacology data model and has begun capturing data on 28 antimalarial ligands. Future plans include expanding the curation, developing an online portal, and submitting data to PubChem to link compounds to publications and make the data more accessible.
An Ondex dataset for in silico drug discoverySimon Cockell
This document describes an Ondex dataset created for in silico drug discovery through data integration. It integrated data from several sources on proteins, drugs, diseases, and their interactions. This dataset is used to rediscover known drug repositioning examples by analyzing semantic motifs, or patterns of concepts and relations that indicate potential new drug uses. As an example, it shows how chlorpromazine's second approved use as an anti-emetic can be uncovered through its similarity to trimeprazine, which is known to bind the Histamine H1 Receptor. The integrated dataset and semantic motif approach provide new opportunities to systematically propose additional therapeutic uses of existing drugs.
Presented at the Bioinformatics Seminar at the University of Arkansas, Little Rock on November 5, 2021.
PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical database at the National Library of Medicine, National Institutes of Health. Arguably, PubChem is one of the largest chemical information resources in the public domain, with 111 million unique chemical structures, 1.39 million biological assays, and 292 million biological activity result outcomes. It also contains significant amounts of scientific research data and the inter-relationships between chemicals, proteins, genes, scientific literature, patents, and more. PubChem is a key resource for big data in chemistry and has been used in many studies for developing bioactivity and toxicity prediction models, discovering polypharmacologic (multi-target) ligands, and identifying new macromolecule targets of compounds (for drug-repurposing or off-target side effect prediction). It has also been used for cheminformatics education as well as chemical health and safety training. This presentation provides a high-level overview of PubChem’s data, tools, and services.
Analysing curated protein targets: Partitioning the drugged and the druggable Chris Southan
The document summarizes the Guide to Pharmacology (GtoPdb) database, which curates ligand-protein interaction data from the literature. The database captures interactions between 1460 proteins and 7733 ligands from over 5000 references. It facilitates analysis of drug targets and comparison of druggable targets with compounds tested in vivo. The document then analyzes the genome ontology classifications of targets in the database compared to all human proteins, showing enrichment of receptors, enzymes and transporters in druggable targets. It also provides breakdowns of target characteristics like pathway membership and transmembrane domains. Finally, it uses Venn diagrams to compare targets of approved drugs with high vs. low affinity ligands, showing high-affinity drugs are biased toward receptors.
The GtoImmuPdb Portal aims to provide a unique access point for immunological data within the Guide to Pharmacology (GtoPdb) database. It will contain expert-curated immunological information on protein targets and ligands tagged as immunologically relevant. The portal will assist in identifying potential drug targets and experimental molecules for testing, and will link targets and ligands to immunological processes, cell types, and related diseases. A beta version of GtoImmuPdb is scheduled for release in Spring 2017.
Poster on GtoImmuPdb presented at European Congress of Immunology (Amsterdam, Sep 2018). Overview of the main data types and features included in this extension to the IUPHAR/BPS Guide to PHARMACOLOGY
Presentation by Dr. Elena Faccenda on the IUPHAR/BPS Guide to Immunopharmacology at the 39° Congresso Nazionale della Società Italiana di Farmacologia in Florence, Nov 2019
This document discusses the IUPHAR/BPS Guide to Pharmacology database and related resources. It provides open access information on pharmacological targets and the substances that act on them. It includes over 1,700 human drug targets, 9,700 ligands including 1,300 approved drugs. Related databases include the Guide to Immunopharmacology and Guide to Malaria Pharmacology. The databases are regularly updated and include links to other resources to enable interoperability.
This document describes updates to the Guide to PHARMACOLOGY (GtoPdb) database in 2017, including new features such as:
1) Organization of drug targets into families and subclasses for easier browsing, and organization of ligands into related families and groups.
2) Ability to visualize ligand binding affinities across species through activity graphs.
3) SynPHARM database for finding ligand binding sequences that can be engineered into synthetic proteins.
4) Expanded content with over 1,700 drug targets, 9,000 ligands, and options to search or download data in various formats.
Neglected infectious diseases such as tuberculosis (TB) and malaria kill millions of people annually and the oral drugs used are subject to resistance requiring the urgent development of new therapeutics. Several groups, including pharmaceutical companies, have made large sets of antimalarial screening hit compounds and the associated bioassay data available for the community to learn from and potentially optimize. We have examined both intrinsic and predicted molecular properties across these datasets and compared them with large libraries of compounds screened against Mycobacterium tuberculosis in order to identify any obvious patterns, trends or relationships. One set of antimalarial hits provided by GlaxoSmithKline appears less optimal for lead optimization compared with two other sets of screening hits we examined. Active compounds against both diseases were identified to have larger molecular weight ([similar]350–400) and logP values of [similar]4.0, values that are, in general, distinct from the less active compounds. The antimalarial hits were also filtered with computational rules to identify potentially undesirable substructures. We were surprised that approximately 75–85% of these compounds failed one of the sets of filters that we applied during this work. The level of filter failure was much higher than for FDA approved drugs or a subset of antimalarial drugs. Both antimalarial and antituberculosis drug discovery should likely use simple available approaches to ensure that the hits derived from large scale screening are worth optimizing and do not clearly represent reactive compounds with a higher probability of toxicity in vivo.
PubChem for drug discovery and chemical biologyChris Southan
This document provides an overview of the PubChem database for academic drug discovery and chemical biology. It describes PubChem's large content of over 97 million compounds and 3.4 million with bioactivity results. It highlights drug-related resources in PubChem like ChEMBL and the Guide to Pharmacology. It also demonstrates several use cases, including searching structures extracted from patents, linking between papers and chemistry, and getting probes mapped into PubChem.
Antimalarial drug dscovery data disclosureChris Southan
Dr. Christopher Southan presented on comparing open and closed antimalarial drug discovery approaches. He examined 32 recent antimalarial compounds and found major data connectivity issues, such as leads not being findable by code name or having publications not citing patents. In contrast, the open source Sydney University Malaria Project surfaces structures and shares data in near real-time through open lab books and crowdsourcing. Dr. Southan analyzed their collection of 411 molecules and found 250 matched in PubChem quickly. Open approaches can accelerate discovery by years by openly sharing data.
Updated poster following beta v3 release. In preparation for Pharmacology Futures, Edinburgh Immunology Symposium and Word Congress of Pharmacology (Kyoto)
This study aimed to identify existing drug therapies that could potentially be repurposed to treat gastric cancer. Differentially expressed genes from microarray analyses of gastric cancer tissue samples were submitted to the Connectivity Map database to identify candidate drugs that could reverse disease signatures. Vorinostat and trichostatin A, both histone deacetylase inhibitors, were predicted as potential therapies based on their expression profiles opposing those of gastric cancer tumors. Future work will integrate biological pathway knowledge to link predicted drugs to relevant pathways.
IUPHAR/BPS Guide to Pharmacology: concise mapping of chemistry, data, and tar...Chris Southan
The document summarizes the IUPHAR/BPS Guide to Pharmacology (GtoPdb) database, which maps relationships between chemistry, data, and protein targets. It has evolved from earlier databases to now include over 1500 human protein targets linked to ligand data. Challenges include resolving relationships across different target hierarchies and filling data gaps. Future plans include expanding the database and linking it to immunopharmacology data through a new Guide to Immunopharmacology portal.
Poster titled "The imperative of small, high quality data for underpinning big data: the IUPHAR/BPS Guide to PHARMACOLOGY". Presented by Dr. Christopher Southan, at the British Society of Pharmacology, Institute for Translational Medicine & Therapeutics (ITMAT) Meeting, Edinburgh, March 2017, ‘Big Data & the Development of New Medicines’.
This document discusses databases that define the druggable proteome - the portion of the human proteome that can bind small molecules with sufficient affinity for modulating protein function. Four databases - ChEMBL, BindingDB, DrugBank, and IUPHAR/BPS Guide to PHARMACOLOGY - provide evidence-supported links between human proteins and drug targets. Their intersection identifies ~490 proteins (13% of the union of targets) as the most precisely defined druggable proteome. Comparative analyses examine distributions of targets by function and other attributes. Initiatives aim to expand knowledge of currently unannotated but potentially druggable protein families to broaden therapeutic opportunities.
Guide to PHARMACOLOGY: a web-Based Compendium for Research and EducationChris Southan
This document summarizes a presentation about the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) database. The following key points are made:
- GtoPdb is an online resource containing information on over 8,000 ligands and their interactions with around 1,500 human protein targets. It has been used widely by researchers and educators since 2009.
- The database contains detailed information on drug targets like GPCRs, ion channels, and enzymes. It also provides data on ligands, drugs, interactions between ligands and targets, and related clinical information.
- Users can browse targets and ligands or search the database. Detailed target pages contain pharmacology data, mechanisms, and links
Curatorial data wrangling for the Guide to PHARMACOLGY Chris Southan
This document discusses the challenges and experiences of curating quantitative target-ligand interaction data for the Guide to PHARMACOLOGY database from the primary literature. Standardizing entities such as proteins, ligands, and measurement units across different data sources can be difficult due to inconsistencies in naming, identifiers, and reporting of values. Initiatives by publishers to have authors mark up key entities in manuscripts may help curators but will not solve all compatibility issues. The curation process also requires judgment calls on issues like resolving conflicts between data sources and determining whether reported data can be structurally defined.
The IUPHAR/MMV Guide to Malaria Pharmacology Chris Southan
This document summarizes the creation of the IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb) database by the authors. It captures antimalarial compounds, targets, and their relationships by curating data from publications. The database has adapted the Guide to Pharmacology data model and has begun capturing data on 28 antimalarial ligands. Future plans include expanding the curation, developing an online portal, and submitting data to PubChem to link compounds to publications and make the data more accessible.
An Ondex dataset for in silico drug discoverySimon Cockell
This document describes an Ondex dataset created for in silico drug discovery through data integration. It integrated data from several sources on proteins, drugs, diseases, and their interactions. This dataset is used to rediscover known drug repositioning examples by analyzing semantic motifs, or patterns of concepts and relations that indicate potential new drug uses. As an example, it shows how chlorpromazine's second approved use as an anti-emetic can be uncovered through its similarity to trimeprazine, which is known to bind the Histamine H1 Receptor. The integrated dataset and semantic motif approach provide new opportunities to systematically propose additional therapeutic uses of existing drugs.
Presented at the Bioinformatics Seminar at the University of Arkansas, Little Rock on November 5, 2021.
PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical database at the National Library of Medicine, National Institutes of Health. Arguably, PubChem is one of the largest chemical information resources in the public domain, with 111 million unique chemical structures, 1.39 million biological assays, and 292 million biological activity result outcomes. It also contains significant amounts of scientific research data and the inter-relationships between chemicals, proteins, genes, scientific literature, patents, and more. PubChem is a key resource for big data in chemistry and has been used in many studies for developing bioactivity and toxicity prediction models, discovering polypharmacologic (multi-target) ligands, and identifying new macromolecule targets of compounds (for drug-repurposing or off-target side effect prediction). It has also been used for cheminformatics education as well as chemical health and safety training. This presentation provides a high-level overview of PubChem’s data, tools, and services.
Analysing curated protein targets: Partitioning the drugged and the druggable Chris Southan
The document summarizes the Guide to Pharmacology (GtoPdb) database, which curates ligand-protein interaction data from the literature. The database captures interactions between 1460 proteins and 7733 ligands from over 5000 references. It facilitates analysis of drug targets and comparison of druggable targets with compounds tested in vivo. The document then analyzes the genome ontology classifications of targets in the database compared to all human proteins, showing enrichment of receptors, enzymes and transporters in druggable targets. It also provides breakdowns of target characteristics like pathway membership and transmembrane domains. Finally, it uses Venn diagrams to compare targets of approved drugs with high vs. low affinity ligands, showing high-affinity drugs are biased toward receptors.
The GtoImmuPdb Portal aims to provide a unique access point for immunological data within the Guide to Pharmacology (GtoPdb) database. It will contain expert-curated immunological information on protein targets and ligands tagged as immunologically relevant. The portal will assist in identifying potential drug targets and experimental molecules for testing, and will link targets and ligands to immunological processes, cell types, and related diseases. A beta version of GtoImmuPdb is scheduled for release in Spring 2017.
IUPHAR Guide to IMMUNOPHARMACOLOGY poster. Presented at the BSI Congress 2017, Brighton, UK (6th December 2017) and at Pharmacology 2017, London, UK (13th December 2017.
Drug-to-protein mappings in the Guide to PHARMACOLOGY: Utility as a target va...Guide to PHARMACOLOGY
The Guide to Pharmacology database (GtoPdb) provides expertly curated information on drug-protein interactions and targets of approved and investigational drugs. It currently includes data on interactions between over 1400 protein targets and 7700 ligands derived from over 5000 literature references. The database covers major target classes and provides a useful resource for target validation and drug discovery. Future plans include regular updates with new target and drug data as well as potential specialty sub-portals within the database.
New Drug Design & Discovery discusses the process of drug discovery and design. It begins with an introduction to how drugs work in the human body to modulate functions. The drug discovery process is then described as a long, expensive endeavor involving chemical synthesis, clinical development, and formulation. Computer-aided drug design uses molecular modeling and structure-based approaches to predict ligand-receptor binding and identify biological targets in silico. Combinatorial chemistry and high-throughput screening allow for the rapid synthesis and testing of large libraries of compounds. The goal is to develop more potent and safer drugs through these computational and high-throughput methods.
The document discusses various topics related to new drug development and pharmacogenomics. It covers the stages of new drug development including drug discovery, pre-clinical research, clinical trials, FDA review and post-marketing monitoring. It also discusses pharmacogenomics and how genetic factors can influence individual responses to drugs. Key aspects like drug screening, clinical trial phases, reasons for drug failure, and the role of animal models in pre-clinical research are summarized.
Assessing GtoPdb ligand content in PubChemChris Southan
The document discusses the content of ligands from the IUPHAR/BPS Guide to PHARMACOLOGY database (GtoPdb) that is contained within PubChem. It finds that GtoPdb ligands have extensive overlap with several other sources within PubChem, including patents, DrugBank, vendor structures, bioassays, and ChEMBL. This overlap allows users to find additional information on GtoPdb ligands from these complementary sources within PubChem.
A Wellcome Trust-funded project to extend the Guide to PHARMACOLOGY (www.guidetopharmacology.org) to include data on key immunological data types and associate these to drugs and drug targets. Presented at the ELIXIR-UK All-Hand Meeting, Edinburgh, Nov 2017.
Comparing ChEMBL, DrugBank, Human Metabolome db and Therapeutic Target db at ...Chris Southan
Talk given at the Paris NC-IUPHAR meeting, Paris, October 2013
ChEMBL, DrugBank, Human Metabolome Database and the Therapeutic Target Database are resources of curated chemistry-to-protein relationships widely used in the chemogenomic arena. In this work we have extended an earlier analysis (PMID 22821596) by comparing chemistry and protein target content between 2010 and 2013. For the former, details are presented for overlaps and differences, statistics of stereochemistry as well as stereo representation and MW profiles between the four databases. For 2013 our results indicate quality improvements, major expansion, increased achiral structures and changes in MW distributions. An orthogonal comparison of chemical content with different sources inside PubChem highlights further interpretable differences. Expansion of protein content by UniProt IDs is also recorded for 2013 and Gene Ontology comparisons for human-only sets indicate differences. These emphasise the expanding complementarity of chemistry-to-protein relationships between sources, although different criteria are used for their capture.
Study on multi-target mechanism of Radix et Rhizoma Rhei (Dahuang) and Semen ...LucyPi1
Abstract Objective: To explore the mechanism of action of Radix et Rhizoma Rhei (Dahuang) (RERR) and Semen Persicae (Taoren) (SP) on adhesive intestinal obstruction (AIO). Methods: The main targets of the active ingredients of RERR and SP were filtered based on the traditional Chinese medicine system pharmacology analysis platform. Cytoscape 3.2.1 was applied to build the ingredient-target network of RERR and SP for AIO. Results: Fifteen active components were predicted from the RERR and SP herb pair, such as aloe-emodin, catechin, rhein, gibberellin (GA) 119, GA120 and GA121. These components were applied to 59 targets mainly involved in many biological processes such as signal transduction, anti-apoptosis, and inflammatory response involved in activating the immune effect. Conclusion: This study proposes the system pharmacology method and identifies the potent combination therapeutic mechanism of RERR and SP for AIO. This strategy will provide a new insight to the study of herb combinations.
This document provides information about searching for evidence in medical literature. It discusses what evidence is, various search strategies such as developing search terms and using databases like PubMed. It also covers search techniques in PubMed including using Boolean operators, phrase searching, truncation and developing search strategies for clinical questions. Finally, it briefly introduces Research4Life programs that provide developing countries access to academic publications.
Exploiting Edinburgh's Guide to PHARMACOLOGY database as a source of protein ...Chris Southan
Presented by Jamie Davies at the SULSA Synthetic Biology Meeting, Edinburgh, 10 June 2014
http://www.eventbrite.co.uk/e/sulsa-synthetic-biology-meeting-registration-11251454403?aff=eorg
Abstract: Synthetic creation of new biological systems typically incorporates pathways and signaling modules from known protein building blocks. Testing the models underpinning the synthetic engineering thus needs the experimental manipulation of individual proteins, for example, ablating a specific enzyme activity via RNAi, SNP mutation, or knockout. However, the option of small-molecule inhibition as the system perturbation has the advantages of 1) rapid onset 2) dose-response 3) analog testing for structure-activity relationships, 4) exploring mixtures for combinatorial effects 5) pulsing and reversal by wash-out. 6) accurate measurements of added substances and 7) a vast precedent of published results in natural systems from medicinal chemistry, pharmacology, and chemical biology. For the synthetic biologists the GToPdb1 can thus be considered as compendium of the latter. It encompasses an interaction matrix between ~4000 small molecules and ~1000 human proteins with a focus on drugs, clinical candidates, research compounds and peptide ligands These not only have ~ 10,000 mapped binding constants but also the spectrum of documented modulation extends across enzymes, receptors, channels and transporters. It thus becomes an increasingly plausible option to choose a “Lego protein” from GToPdb as a synthetic system component that can have experimentally useable activity probes available from chemical vendors. Even if it does not currently have a suitable target-probe pair, as knowledge base (and expertise resource via the curation team who populate it) GToPdb is an ideal starting point from which to walk out to wider chemogenomic spaces. For example, while an approved drug and its target might seem a logical choice, analogs from the lead series or different chemotypes from which the drug was optimized, or even failed in development, can have superior probe-like properties for in vitro experiments (e.g. be more potent, specific and soluble). The GToPdb facilitates access to such compound data via curated papers and patents.
References
1. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, Davenport AP, McGrath JC, Peters JA, Southan C, Spedding M, Yu W, Harmar AJ; NC-IUPHAR. The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucleic Acids Res. 2014 Jan 1;42(1)
Computer aided drug design uses computational approaches to aid in the drug discovery process. There are several key approaches including ligand based approaches which identify characteristics of known active ligands, target based approaches which use information about the biological target, and structure based drug design which utilizes 3D structural information. The main steps in drug design include target identification and validation, lead identification and optimization, and preclinical and clinical trials. Computational tools are used throughout the process for tasks like molecular docking, ADMET prediction, and structure activity relationship analysis.
Predicting Drug Candidates Safety : the Role and Usage of Knowledge BasesAureus Sciences
- Aureus Sciences builds knowledge bases for predicting drug candidates' safety, focusing on areas like drug-drug interactions, safety pharmacology, and off-target effects.
- They have developed large structured databases of chemical and bioactivity information from literature and provide applications and services to analyze the data for customers in drug development.
- Their predictive models and databases have been shown to accurately predict drug interactions and off-target effects, helping customers optimize drug safety assessment.
Bioinformatics plays an important role in drug discovery and development by enabling target identification, rational drug design, compound refinement, and other processes. Key applications of bioinformatics include virtual screening of large compound libraries to identify potential drug leads, homology modeling of protein structures to inform drug design, and similarity searches to find analogs of existing drug molecules. The overall drug development process involves studying the disease, identifying drug targets, designing compounds, testing and refining candidates, and conducting clinical trials. Computational techniques expedite many steps but experimental validation is still needed.
Collaborative Drug Discovery: A Platform For Transforming Neglected Disease R...Sean Ekins
The document discusses the Collaborative Drug Discovery (CDD) platform, which aims to facilitate data sharing and collaboration in drug discovery. Key points:
- CDD allows users to securely store private data while selectively sharing subsets with collaborators. It also hosts public datasets totaling over 3 million compounds.
- CDD has been used to facilitate collaboration in neglected disease research, particularly for tuberculosis and malaria. It hosts over 15 public TB datasets totaling over 300,000 compounds.
- Analysis of TB and malaria hit compounds on the platform shows generally higher molecular weights and logP values compared to approved drugs. Many compounds also fail filtering for undesirable reactivity.
Pharmacokinetic Properties of Biomass-extracted Substances Isolated by Green ...Michal Jablonsky
According to the literature, approximately 41 nutraceutical compounds have been isolated from different types of biomass using green solvents. It is important to collect information on the pharmacokinetic properties of the nutraceutical substances from biomass isolated according to the published papers. The pharmacokinetic properties of the bioactive substances extracted by green solvents, such as the molecular weight, logP, AlogP, H-bond acceptor, H-bond donor, total polar surface area, atom molar refractivity, number of rotatable bonds, number of atoms, rotatable bond count, number of rigid bonds, number of atom rings, and number of H-bonds, were calculated with a drug-likeness tool. In practical terms, the original and most well-known Lipinski's Rule of Five (Ro5) was applied to 28 substances, namely 3-hydroxytyrosol; apigenin; artemisinin; bergapten; bilobalide; biochanin A; caffeic Acid; caffeoylmalic acid; catechins; cinnamic acid; curcumin; daidzei; daidzin; epicatechin; gallic acid; genistein; ginkgolide A; ginkgolide B; levofloxacin; luteolin; naringenin; p-coumaric acid; protocatechuic acid; psoralen; quercetin; trans-ferulic acid; tyrosol, and vanillin.
The document provides an overview and progress report on database activities from April 2018 - March 2019. Key points include:
- Publications in peer-reviewed journals on the database and new immunopharmacology guide.
- Engagement through conferences, social media, and interactions with users seeking to improve the database.
- Ongoing development of the database interface and content, including expansion to new therapeutic areas.
- Statistics on usage, file downloads, and web service calls that show increasing interaction over time.
Dr. Simon D. Harding of the University of Edinburgh created a knowledge-base that connects immunology and pharmacology. The knowledge-base links immunological targets and ligands to cell types and diseases. It is part of the IUPHAR/BPS Guide to Pharmacology, an open database of drug targets and ligands including approved drugs. A new search tool allows searching of pharmacological information. Dr. Harding also aims to curate data on antimalarial compounds and their molecular targets in Plasmodium through the IUPHAR/MMV Guide to Malaria Pharmacology.
The document provides an overview and status report of the Core Guide to PHARMACOLOGY (GtoPdb) database. It discusses recent publications from the team, compliance with new GDPR privacy regulations, website access statistics showing increased usage, new website features, and priorities for further development such as expanding disease and content coverage.
The document provides a status report on the Guide to Immunopharmacology database (GtoImmuPdb). It discusses developments including the addition of disease data, graphical browsing of cell type data, and process data. The database is in beta version 3 and undergoing user testing. Over 500 targets and 1,000 ligands have been curated from the literature. On the curation side, efforts are focused on expanding the literature collection and annotating new targets and ligands. The database is preparing for its official launch in October 2018.
IUPHAR/BPS Guide to PHARMACOLOGY in 2017: new features and updatesGuide to PHARMACOLOGY
This document summarizes updates to the IUPHAR/BPS Guide to PHARMACOLOGY database. It provides expert curated data on human drug targets and ligands. Recent additions include new target families, ligands, and links to immunopharmacology data. New features include download options, search tools, and organization of ligand families. The database is maintained by an international team and network of scientists and provides a resource for pharmacology education and research.
These slides will be presented at the Pharmacology 2017 meeting in London during the following session:
Abstract Number: OB073
Abstract Title: Capturing new BIA 10-2474 molecular data in the IUPHAR/BPS Guide to PHARMACOLOGY
Date: Wednesday, December 13, 2017, 11:30 AM
Oral Session: Oral Communications: Mixed Tracks
This comprehensive slide deck is provided for use by those who are teaching and presenting on the IUPHAR/BPS Guide to PHARMACOLOGY. Includes:
- Overview of NC-IUPHAR
- Background to GtoPdb
- Screenshots of the website and search tools
- Recent content expansions
- Other features and initiatives including the Guide to IMMUNOPHARMACOLOGY
This slide set updates the previous set from 2014/15 available at https://www.slideshare.net/GuidetoPHARM/iupharbps-guide-to-pharmacology-generic-slideset
Navigating links between structures and papers:
PubMed-to-PubChem connectivity between the IUPHAR/BPS Guide to PHARMACOLOGY and British Journal of Pharmacology
A poster presented at Pharmacology 2017, London, December 2017
A general poster about the IUPHAR/BPS Guide to PHARMACOLOGY, updated for 2017. This works well used as a handout or pinned on departmental noticeboards.
(First slide is recording of webinar). IUPHAR Web Resources, Simplifying Complexity for Medicine and Education. WDS Webinar#11 held on 28th February 2017.
IUPHAR (International Union of Basic and Clinical Pharmacology) has developed and is developing a series of web-based services for the Pharmacological Sciences, for education, and for drug discovery. These services enable the simplification and dissemination of highly complex datasets, via expert committees linked to ontologically-correct databases (e.g., the drug and receptor sites expressed by the human genome). This has also allowed IUPHAR—in connection with the main national pharmacological societies, particularly the British Pharmacological Society—to raise funds for curators and meetings. This simple model is open-ended and is being expanded to, for example, immunological targets and experimental protocols, and to educational projects.
Speakers: Michael Spedding, Adam Pawson, Steve Alexander, Joanna Sharman, Simon Harding, Jamie Davies, John Szarek and Lynn LeCount
Flash poster presentation slide of IUPHAR Guide to PHARMACOLOGY. As presented by Dr. Simon Harding at BPS Pharmacology 2016 @BritPharmSoc @GuidetoPHARM
Dr. Firoozeh Kashani-Sabet is an innovator in Middle Eastern Studies and approaches her work, particularly focused on Iran, with a depth and commitment that has resulted in multiple book publications. She is notable for her work with the University of Pennsylvania, where she serves as the Walter H. Annenberg Professor of History.
Anti-Universe And Emergent Gravity and the Dark UniverseSérgio Sacani
Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
Mechanics:- Simple and Compound PendulumPravinHudge1
a compound pendulum is a physical system with a more complex structure than a simple pendulum, incorporating its mass distribution and dimensions into its oscillatory motion around a fixed axis. Understanding its dynamics involves principles of rotational mechanics and the interplay between gravitational potential energy and kinetic energy. Compound pendulums are used in various scientific and engineering applications, such as seismology for measuring earthquakes, in clocks to maintain accurate timekeeping, and in mechanical systems to study oscillatory motion dynamics.
Embracing Deep Variability For Reproducibility and Replicability
Abstract: Reproducibility (aka determinism in some cases) constitutes a fundamental aspect in various fields of computer science, such as floating-point computations in numerical analysis and simulation, concurrency models in parallelism, reproducible builds for third parties integration and packaging, and containerization for execution environments. These concepts, while pervasive across diverse concerns, often exhibit intricate inter-dependencies, making it challenging to achieve a comprehensive understanding. In this short and vision paper we delve into the application of software engineering techniques, specifically variability management, to systematically identify and explicit points of variability that may give rise to reproducibility issues (eg language, libraries, compiler, virtual machine, OS, environment variables, etc). The primary objectives are: i) gaining insights into the variability layers and their possible interactions, ii) capturing and documenting configurations for the sake of reproducibility, and iii) exploring diverse configurations to replicate, and hence validate and ensure the robustness of results. By adopting these methodologies, we aim to address the complexities associated with reproducibility and replicability in modern software systems and environments, facilitating a more comprehensive and nuanced perspective on these critical aspects.
https://hal.science/hal-04582287
JAMES WEBB STUDY THE MASSIVE BLACK HOLE SEEDSSérgio Sacani
The pathway(s) to seeding the massive black holes (MBHs) that exist at the heart of galaxies in the present and distant Universe remains an unsolved problem. Here we categorise, describe and quantitatively discuss the formation pathways of both light and heavy seeds. We emphasise that the most recent computational models suggest that rather than a bimodal-like mass spectrum between light and heavy seeds with light at one end and heavy at the other that instead a continuum exists. Light seeds being more ubiquitous and the heavier seeds becoming less and less abundant due the rarer environmental conditions required for their formation. We therefore examine the different mechanisms that give rise to different seed mass spectrums. We show how and why the mechanisms that produce the heaviest seeds are also among the rarest events in the Universe and are hence extremely unlikely to be the seeds for the vast majority of the MBH population. We quantify, within the limits of the current large uncertainties in the seeding processes, the expected number densities of the seed mass spectrum. We argue that light seeds must be at least 103 to 105 times more numerous than heavy seeds to explain the MBH population as a whole. Based on our current understanding of the seed population this makes heavy seeds (Mseed > 103 M⊙) a significantly more likely pathway given that heavy seeds have an abundance pattern than is close to and likely in excess of 10−4 compared to light seeds. Finally, we examine the current state-of-the-art in numerical calculations and recent observations and plot a path forward for near-future advances in both domains.
Evaluation and Identification of J'BaFofi the Giant Spider of Congo and Moke...MrSproy
ABSTRACT
The J'BaFofi, or "Giant Spider," is a mainly legendary arachnid by reportedly inhabiting the dense rain forests of
the Congo. As despite numerous anecdotal accounts and cultural references, the scientific validation remains more elusive.
My study aims to proper evaluate the existence of the J'BaFofi through the analysis of historical reports,indigenous
testimonies and modern exploration efforts.
Compositions of iron-meteorite parent bodies constrainthe structure of the pr...Sérgio Sacani
Magmatic iron-meteorite parent bodies are the earliest planetesimals in the Solar System,and they preserve information about conditions and planet-forming processes in thesolar nebula. In this study, we include comprehensive elemental compositions andfractional-crystallization modeling for iron meteorites from the cores of five differenti-ated asteroids from the inner Solar System. Together with previous results of metalliccores from the outer Solar System, we conclude that asteroidal cores from the outerSolar System have smaller sizes, elevated siderophile-element abundances, and simplercrystallization processes than those from the inner Solar System. These differences arerelated to the formation locations of the parent asteroids because the solar protoplane-tary disk varied in redox conditions, elemental distributions, and dynamics at differentheliocentric distances. Using highly siderophile-element data from iron meteorites, wereconstruct the distribution of calcium-aluminum-rich inclusions (CAIs) across theprotoplanetary disk within the first million years of Solar-System history. CAIs, the firstsolids to condense in the Solar System, formed close to the Sun. They were, however,concentrated within the outer disk and depleted within the inner disk. Future modelsof the structure and evolution of the protoplanetary disk should account for this dis-tribution pattern of CAIs.
Sexuality - Issues, Attitude and Behaviour - Applied Social Psychology - Psyc...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
BIRDS DIVERSITY OF SOOTEA BISWANATH ASSAM.ppt.pptxgoluk9330
Ahota Beel, nestled in Sootea Biswanath Assam , is celebrated for its extraordinary diversity of bird species. This wetland sanctuary supports a myriad of avian residents and migrants alike. Visitors can admire the elegant flights of migratory species such as the Northern Pintail and Eurasian Wigeon, alongside resident birds including the Asian Openbill and Pheasant-tailed Jacana. With its tranquil scenery and varied habitats, Ahota Beel offers a perfect haven for birdwatchers to appreciate and study the vibrant birdlife that thrives in this natural refuge.
Evidence of Jet Activity from the Secondary Black Hole in the OJ 287 Binary S...Sérgio Sacani
Wereport the study of a huge optical intraday flare on 2021 November 12 at 2 a.m. UT in the blazar OJ287. In the binary black hole model, it is associated with an impact of the secondary black hole on the accretion disk of the primary. Our multifrequency observing campaign was set up to search for such a signature of the impact based on a prediction made 8 yr earlier. The first I-band results of the flare have already been reported by Kishore et al. (2024). Here we combine these data with our monitoring in the R-band. There is a big change in the R–I spectral index by 1.0 ±0.1 between the normal background and the flare, suggesting a new component of radiation. The polarization variation during the rise of the flare suggests the same. The limits on the source size place it most reasonably in the jet of the secondary BH. We then ask why we have not seen this phenomenon before. We show that OJ287 was never before observed with sufficient sensitivity on the night when the flare should have happened according to the binary model. We also study the probability that this flare is just an oversized example of intraday variability using the Krakow data set of intense monitoring between 2015 and 2023. We find that the occurrence of a flare of this size and rapidity is unlikely. In machine-readable Tables 1 and 2, we give the full orbit-linked historical light curve of OJ287 as well as the dense monitoring sample of Krakow.
SDSS1335+0728: The awakening of a ∼ 106M⊙ black hole⋆Sérgio Sacani
Context. The early-type galaxy SDSS J133519.91+072807.4 (hereafter SDSS1335+0728), which had exhibited no prior optical variations during the preceding two decades, began showing significant nuclear variability in the Zwicky Transient Facility (ZTF) alert stream from December 2019 (as ZTF19acnskyy). This variability behaviour, coupled with the host-galaxy properties, suggests that SDSS1335+0728 hosts a ∼ 106M⊙ black hole (BH) that is currently in the process of ‘turning on’. Aims. We present a multi-wavelength photometric analysis and spectroscopic follow-up performed with the aim of better understanding the origin of the nuclear variations detected in SDSS1335+0728. Methods. We used archival photometry (from WISE, 2MASS, SDSS, GALEX, eROSITA) and spectroscopic data (from SDSS and LAMOST) to study the state of SDSS1335+0728 prior to December 2019, and new observations from Swift, SOAR/Goodman, VLT/X-shooter, and Keck/LRIS taken after its turn-on to characterise its current state. We analysed the variability of SDSS1335+0728 in the X-ray/UV/optical/mid-infrared range, modelled its spectral energy distribution prior to and after December 2019, and studied the evolution of its UV/optical spectra. Results. From our multi-wavelength photometric analysis, we find that: (a) since 2021, the UV flux (from Swift/UVOT observations) is four times brighter than the flux reported by GALEX in 2004; (b) since June 2022, the mid-infrared flux has risen more than two times, and the W1−W2 WISE colour has become redder; and (c) since February 2024, the source has begun showing X-ray emission. From our spectroscopic follow-up, we see that (i) the narrow emission line ratios are now consistent with a more energetic ionising continuum; (ii) broad emission lines are not detected; and (iii) the [OIII] line increased its flux ∼ 3.6 years after the first ZTF alert, which implies a relatively compact narrow-line-emitting region. Conclusions. We conclude that the variations observed in SDSS1335+0728 could be either explained by a ∼ 106M⊙ AGN that is just turning on or by an exotic tidal disruption event (TDE). If the former is true, SDSS1335+0728 is one of the strongest cases of an AGNobserved in the process of activating. If the latter were found to be the case, it would correspond to the longest and faintest TDE ever observed (or another class of still unknown nuclear transient). Future observations of SDSS1335+0728 are crucial to further understand its behaviour. Key words. galaxies: active– accretion, accretion discs– galaxies: individual: SDSS J133519.91+072807.4
Presentation of our paper, "Towards Quantitative Evaluation of Explainable AI Methods for Deepfake Detection", by K. Tsigos, E. Apostolidis, S. Baxevanakis, S. Papadopoulos, V. Mezaris. Presented at the ACM Int. Workshop on Multimedia AI against Disinformation (MAD’24) of the ACM Int. Conf. on Multimedia Retrieval (ICMR’24), Thailand, June 2024. https://doi.org/10.1145/3643491.3660292 https://arxiv.org/abs/2404.18649
Software available at https://github.com/IDT-ITI/XAI-Deepfakes
1. 3. Searching for targets and ligands
2. Current database content
8. References
1
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK. 2
School of Life Sciences, University of Nottingham Medical School, Nottingham, UK. 3
Experimental Medicine and
Immunotherapeutics, University of Cambridge, Cambridge. 4
Spedding Research Solutions SAS, Le Vesinet, France. * The International Union of Basic and Clinical Pharmacology Committee on
Receptor Nomenclature and Drug Classification.
The IUPHAR/BPS Guide to PHARMACOLOGY
1. Introduction
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) is an open, expert-driven database of
pharmacological targets and the substances that act on them [1]. It is a joint initiative between
the British Pharmacological Society (BPS) and the International Union of Basic and Clinical
Pharmacology (IUPHAR), which aims to cover the human targets of licensed drugs and other
likely targets of future therapeutics.
The information is presented at two levels:
1. Overviews of the key properties, selective ligands and further reading for a wide range of
human biological targets, which forms the basis for the Concise Guide to PHARMACOLOGY
(CGTP) [2].
2. Detailed pharmacological, functional and clinical information for a subset of important
targets.
All data are curated from the primary literature by an international network of 500 experts in
96 subcommittees of the IUPHAR Committee on Receptor Nomenclature and Drug
Classification (NC-IUPHAR).
~1,700 established or potential data-supported drug targets
~1,100 additional related proteins
Across several target classes: GPCRs, NHRs, Enzymes, Ion-Channels, Catalytic Receptors,
Transporter and other protein targets
Various search tools are available to find targets and ligands by name, ID, reference, chemical
structure similarity, or BLAST sequence search. A new Pharmacology Search Tool (Fig. 2) allows
users to upload lists of protein IDs and find ligands that modulate them, from both the GtoPdb
and ChEMBL [3] databases.
1. Harding SD, et al. (2018). Nucl. Acids Res. 46 (Issue D1): D1091-D1106.
2. Alexander SPH, et al. (2017). Br J Pharmacol. 174 (Suppl 1): S1-S446.
3. Bento AP, et al. (2014). Nucl. Acids Res. 42 (Database Issue): D1083-D1090.
4. Harding SD, et al. (2018). Nat Rev Immunol. Web Watch: https://doi.org/10.1038/s41577-018-0079-2
5. Medicines for Malaria Venture https://www.mmv.org/
In addition, for a “how-to” guide on using GtoPdb see: Sharman JL, et al. (2018) Curr Protoc Bioinformatics. 61: 1.34.1-1.34.46.
5. IUPHAR Guide to Immunopharmacology
Launched in October 2018, the Wellcome Trust-funded IUPHAR Guide to Immunopharmacology
(GtoImmuPdb; www.guidetoimmunopharmacology.org) extends the information stored about
drug targets by associating them with processes, cell types and disease of relevance to
immunology.
Providing a knowledge base that, for the first time, connects immunology with pharmacology [4].
Christopher Southan1
, Simon D. Harding1
, Jane F. Armstrong1
, Elena Faccenda1
, Adam J. Pawson1
, Stephen P.H. Alexander2
,
Anthony P. Davenport3
, Michael Spedding4
, Jamie A. Davies1
and NC-IUPHAR*
6. IUPHAR/MMV Guide to Malaria Pharmacology
www.guidetopharmacology.org enquiries@guidetopharmacology.org @GuidetoPHARM
4. Comparing ligand affinity across species
Ligand activity graphs provide a quick way to visualise affinity at different targets and across
species. Box plots (Fig. 2A) summarise standardised activity data from GtoPdb and ChEMBL [3].
Individual data points, assay details and references are provided in an accompanying table (Fig.
2B).
Figure 2. Chart and table showing palosuran activity at human and rat UT receptors.
A
B
7. Downloading data
Data are available to download in various formats:
• Lists of targets, ligands and interactions in CSV format
• REST web services for computational access to data in JSON format
• SQL database dump files
• Interaction data are now available in RDF format for semantic integration
~9,400 ligands, over 7,000 with quantitative interaction data
Includes experimental compounds, labelled ligands,
antibodies, peptides, natural products and inorganic
chemicals
> 1,300 approved drugs, >800 with quantitative interaction
data
Figure 1. (A) Pharmacology Search Tool with
searching restricted to 3 interactions per
target. (B) Results show activity data
summarised from GtoPdb and ChEMBL.
Results from searches can be downloaded
as a CSV file by clicking the Download
button in the top right.
540 targets and over 1,000 ligands of relevance to
immunopharmacology.
700 associations between ligands and disease
3,000 target to immuno process associations
300 target to cell type associations
This expert curation seeks to bring the most valuable
pharmacological data into the hands of immunology
researchers, facilitating the crossover of their research
into drug discovery and therapeutics
A
B
We especially thank all contributors, collaborators and NC-IUPHAR members
Since October 2017, collaboration between IUPHAR and Medicines for Malaria
Venture (MMV) [5] to curate antimalarial compounds and Plasmodium molecular
targets for approved drugs.
To provide optimised access to GtoPdb data for the malaria research community.
Key Features
• Provides a unique access point to the
antimalarial information in our expert-curated
database
• Designed in consultation with malaria
researchers to provide tailored routes into
browsing the antimalarial data
• New customised views of the data have been
developed that include parasite lifecycle stage
and target species activity (shown below)
Currently there are 57 antimalarial ligands
curated in the database, covering 25 Plasmodium
molecular targets.
We submit all our curated antimalarial
compounds, that include approved drugs, clinical
candidates and research leads, to PubChem
where they acquire GtoPdb-specific Substance
Identifiers (SIDs). These currently merge into 57
Compound Identifiers (CIDs) that are fully
searchable in PubChem.