News
March 31, 2021
Major P&D release with probe scores, redesigned compound detail and brand new compound sets

Today, we released P&D 02.2021 with several major updates including our brand new P&D probe-likeness score integrated together with scores from Probe Miner and Chemical Probes Portal, total redesign of the compound detail view, and two new focused compound sets.

P&D probe-likeness score (PDP score) is a value, ranging from 0 to 100%, calculated for compounds labelled as probes for each of their directly annotated human target of interest (if specified). It consists of 6 parameters (partial scores): potency, selectivity, cell-potency, control compound, orthogonal probe and structural alerts, and a synergy part of the score. Finally, the PDP score is simply a sum of all of its parts. If a PDP score for a compound-target pair is larger than 70% (not equal or larger, but LARGER), the compound is labelled as P&D approved. The score is designed in a way that the 70% threshold can't be surpassed if the compound is not potent, cell-potent on target and selective at the same time. You can easily filter all P&D approved chemical probes using the P&D approved tag. If you want to know the exact setting of the PDP score and its parameters, you can find it in the FAQ section.

However, PDP score is not the only probe score you can find at the P&D portal. From the current version, we also integrated the Probe Miner score (PMI score) and Chemical Probes Portal Ratings for use in cells (CPO cells) and organisms (CPO organisms). For better comparability, all score values are normalized to range from 0% to 100%, e.g., 3 out of 4 stars in CPO ratings is converted to 75%. All integrated scores can be easily used to filter/order compounds by clicking on the score or through the search field. For example, to filter all probes with at least 3 out of 4 stars at Chemical Probes  Portal with P&D approved probes is as simple as this. Since there can be multiple multiple values for PMI and PDP scores, evaluating each target pair separately, the highest of these values for each compound is used for filtering needs.

The compound detail pages went through a total redesign to include all data associated with the compound with a focus on probe/probe-like compounds. Apart from sections all compound detail pages share, such as targets, compound sets and external links, chemical probe pages include probe-specific sections including probe scores, control compound, orthogonal probes (probes for the same target/s not sharing the same scaffold with structural similarity up to 40%) ordered by their PDP score and similar probes (probes for the same target not in orthogonal probes).

Apart from all major data sources being updated to their last versions (ChEMBL 28, Guide to Pharmacology 2021.1 or DrugBank 5.1.8) and many updated compound sets, we also added two brand new focused compound sets to our collection: IPPI - DB and Nuisance compounds in cellular assays

IPPI - DB (Inhibitors of Protein-Protein Interaction Database), developed and maintained at Institut Pasteur, is a database of modulators of protein-protein interactions. It contains exclusively small molecules and therefore no peptides. The data are retrieved from the literature either peer-reviewed scientific articles or world patents.

Nuisance compounds in cellular assays is a set of compounds extracted from a paper of the same name published by Jayme L. Dahlin in Cell Chemical Biology in Feb 2021. The supplemental information contained a set of more than 1,200 compounds that exhibit assay interference or undesirable mechanisms of bioactivity (“nuisance compounds”) that are routinely encountered in cellular assays, including phenotypic and high-content screening assays. Apart from the set itself, we also systematically integrated different "nuisance" classes into our structural alerts. They can be now easily used to filter compounds tagged as luciferase inhibitors, tubulin modulators, compounds optically interfering with the assay, and many others.

As the last thing, we also added two new sources to our external links.  First, we added links to the COCONUT database (COlleCtion of Open Natural Products) which is an open-source project for Natural Products (NPs) storage, search and analysis, combining data from more than 50 open natural product resources. Second, we used a set of in-stock compounds kindly provided to us by Chemspace (the largest online catalogue of small molecules) to link to this resource and also to tag all matched compounds in P&D as available (we also use data from Mcule, MolPort and up-to-date commercial compound sets).

The database dump including all new data is available in the Download section of the portal and can be freely used under the CC BY-SA 4.0 license.

We hope you find the new data and features useful, and if you have any suggestions for new functions or compound sets we could integrate into our database, please, let us know through the contact form or through our Twitter account (@probesanddrugs).

Jan. 8, 2021
First P&D release in 2021 with covalent binders, biased GPCR ligands and PROTACs

In the first version of P&D in 2021 (ver. 01.2021), you can find a lot of new data concerning not only new compounds (two new specific compound sets - CovalentInDB and PROTAC-DB, and several updated ones, such as Guide to Pharmacology 2020.05, Chemical Probes.org, or Probe Miner), but also new systematic compound annotations of 1) covalent binders (CovalentInDB), 2) biased GPCR ligands (BiasDB), and 3) PROTACs (PROTAC-DB), and also activity data and MOA annotations extracted right from the compound set source data files.

The first new compound set integrated to P&D is the database of covalent binders, CovalentInDB (Covalent Inhibitor Database), published in the last Nucleic Acid Research Database Issue: CovalentInDB: a comprehensive database facilitating the discovery of covalent inhibitors. CovalentInDB is the largest web-accessible resource for covalent inhibitors and related targets. The latest version provides the information for 4511 covalent inhibitors and 280 related protein targets collected by comprehensive literature searching. The inhibitors in CovlnDB possess 57 types of reactive warheads, including Michael acceptor, beta-lactam, boronic acid, epoxide, halohydrocarbon, etc. 

The data from CovalentInDB were used for the direct annotation of the compound-target covalent binding which is highlighted by the covalent bond icon next to the compound's target (see the picture below). Also, activity values with currently accepted activity types (such as IC50, EC50, Ki, etc.) were uploaded to the P&D database. All compounds from the CovalentInDB were automatically labeled with the covalent binder compound type tag.

Another very specific compound set present in the last version of P&D is the PROTAC-DB, also published in the last NAR DB issue (by the same lab as the CovalentInDB): PROTAC-DB: an online database of PROTACs. PROTACs (Proteolysis-targeting chimeras), which induce targeted protein degradation by the ubiquitin-proteasome system, represent a new therapeutic strategy. Unlike traditional small-molecule strategies, which exert their efficacy mainly through binding site occupancy, PROTACs target the specific protein for degradation, thus also eliminating other functions of the protein. In addition, while some small molecules are restricted to bind to the catalytic pocket, PROTACs are capable of utilizing all surface binding pockets on the targeted protein for degradation. 

All compounds from the PROTAC-DB were automatically labeled with the PROTAC compound type tag.

Besides CovalentInDB and PROTAC-DB, additional data were extracted from several other already established sets:

1) BiasDB - direct annotation of the biased GPCR ligands and their targets along with their specific bias, i.e., you can filter biased GPCR ligands with a bias for β-Arrestin over Gi protein or vice-versa. The biased GPCR signaling is highlighted by the biased icon next to the compound's target (see the picture below).

2) PKIDB - direct annotation of inhibited targets with the MOA set as an inhibitor

3) Kinase Chemogenomic Set (KCGS) - direct annotation of inhibited targets with the MOA set as an inhibitor

4) Open Science Probes (SGC Donated Probes) - both biochemical and cell-based activity values along with reference publications

In the future, we are planning to continue with the extraction of activity/MOA information right from the source data files, since many of these can't be found in any of the used bioactivity databases. We also plan to expand the list of accepted activity types with the percentage inhibition/activation of targets (already present in the database dump).

If you have any suggestions for new functionality or compound sets we could include in our database, please, let us know through the contact form or through our Twitter account (@probesanddrugs).

We are wishing you a happy and healthy year 2021!

 

Sept. 24, 2020
P&D 03.2020 released with the Probes tab, probe criteria filters and advanced export

On September 22nd, a new version of P&D portal (03.2020) was released with some major data and functionality updates, among these with a new Probes tab, probe criteria filters, and an advanced export.

Concerning the data updates, all of the major data sources were updated to their current versions (ChEMBL 27GtoPDB 2020.03DrugBank 5.1.7, and others) along with many of the compound sets, including the probe sets such as Chemical probes.orgOpen Science ProbesSGC probes, and opnMe portal. We also added one brand new compound set of biased GPCR ligands from BiasDB (BiasDB: A Comprehensive Database for Biased GPCR Ligands). "BiasDB is a manually curated database containing all published biased GPCR ligands. BiasDB currently contains 654 bias cases of signaling bias representing 489 individual ligands for 61 receptors. We provide information about the chemical structure, target receptor, type of bias, assay categories used for bias determination, reference ligand, and literature source. BiasDB is a resource for medicinal chemists, pharmacologists, and researchers interested in biased GPCR signaling."

One of the major functionality updates is the addition of the Probes tab in the Compounds view along with probe specific filters: probe criteria and probe targets. In the Probes tab, all probe specific filters are pre-loaded to be applied on a pre-filtered set of probes.

There are many possible criteria that can be considered when labeling compounds as chemical probes. On P&D, we tag compounds as probes based on their membership in one of the probe sets (i.e., all compounds that belong to a probe set, such as Chemical probes.org or SGC probes, are tagged as probes), and the provided probes criteria filters can be used to filter them based on the available data. Currently, there are 8 probe criteria filters available (name - description):

  1. Potency >= 7 [100 nM] - potency in a biochemical assay greater than 100 nM (value 7 on a -log() scale).

  2. Cell potency >= 6 [1 µM] [ON TARGET] - on-target potency in a cell-based assay (i.e., potency in a cell-based assay with a specified protein target) greater than 1 µM (value 6 on a -log() scale).

  3. Cell potency >= 6 [1 µM] [GLOBAL] - potency in a cell-based assay (i.e., potency in any cell-based assay) greater than 1 µM (value 6 on a -log() scale).

  4. Is selective [> 30 fold] - selectivity for the probe target is at least 30-fold (~1,47 difference on a -log() scale).

  5. Has inactive control - defined inactive control in the compound’s source data.

  6. Has orthogonal probe - there is at least one other probe for the same target that doesn’t share the same molecular scaffold and is at most 40% similar to the first probe (ECFP4, Tanimoto similarity).

  7. No alert [PAINS/Aggregator] - the probe doesn’t contain any PAINS alert and/or is not tagged as an aggregator.

  8. Not obsolete - the probe is not tagged as obsolete.

These filters can be used in the Probes tab, but, like any other filter, also in the main tab (either found through the text search or added from the Probes tab).

From version 03.2020, the Export functionality was also upgraded. Beside basic compounds’ information, now, it is also possible to export their associated target data for protein targets in two formats, text (.csv) and Excel file (.xlsx). In the target file, there are not only information about target/gene name, activity value, MOA, and probe tag, but also its classification in the ChEMBL/GtoPBD target trees and associated Reactome pathways.

For most of the single protein targets, we also added a target card with the target description (UniProt), classification in available target trees (ChEMBL, GtoPDB, and Slim Gene Ontology), and a list of the underlying targets from different databases. To show the target card, just click on the information icon next to the target name.

Another upgrade that you might notice is an improved UI for the visualizations, where you can now export the image of the whole visualization, and in physico-chemical properties distribution, you can use the add button to compare different filtered compound sets. For example, you can compare PCP distributions for approved drugs approved before and after 1990 (see the picture below):

As a minor upgrade, we added the XOR (eXclusive OR) operator to the current Boolean operators. Using this operator, you can filter compounds that belong to one set or the other, but not to both of them at once. For example, you can filter compounds that bind selectively to Estrogen receptor alpha or Estrogen receptor beta, but not to both of them.

Finally, the database dump with all new data is as always available in the Download section of the portal and can be freely used under the CC BY-SA 4.0 license.

We hope you find the new data and features useful, and if you have any suggestions for new functions or compound sets we could include in our database, please, let us know through the contact form or through our Twitter account (@probesanddrugs).

May 13, 2020
P&D 02.2020 is out with ChEMBL 26, GtoPDB 2020.02, DrugBank 5.1.6, new probes and new compound sets.

In the second version of P&D this year, we updated our database to all new versions of our main data sources: ChEMBL 26GtoPDB 2020.02DrugBank 5.1.6, and BindingDB 04.2020. Along with this, we also added two new compound sets (EU-OPENSCREEN Bioactive Compound LibraryNovartis Chemogenetic Library (NIBR MoA Box)), updated some of the current ones with brand new probes (opnMe PortalOpen Science Probes), and fixed a few structures in the MLP Probes set.

EU-OPENSCREEN ERIC (EU-OS) is a non-profit research infrastructure, which operates on a global scale. It is funded by European countries and offers access to academic high-throughput screening facilities and medicinal chemistry groups in these countriesEU-OS Bioactive Compound Library is a part of the EU-OSpilot library and, since our institute (IMG ASCR) is an EU-OS partner site, the library was selected from the compounds and data in the P&D database (~4,500 selected originally, the final set selected as a part of a public tender) with an emphasis on wide target coverage and selectivity.

Novartis Chemogenetic Library aka NIBR MoA Box extracted from the paper by Stephen M. Canham et al., Systematic chemogenetic library assembly, is a library assembled through data mining and crowdsourcing institutional expertise. The library is available for open collaborations with external partners through the Novartis’ facilitated access to screening technologies (FAST) group. 

Besides new probes in the opnMe Portal and Open Science Probes sets, thanks to Adam Yasgar from NCATS, we were also able to fix 5 wrong structures in the MLP Probes set.

Finally, the database dump with all new data is as always available in the Download section of the portal and can be freely used under the CC BY-SA 4.0 license.

We hope you find the new data useful, and if you have any suggestions for new functions or compound sets we could include in our database, please, let us know through the contact form or through our Twitter account (@probesanddrugs).

 

Feb. 14, 2020
P&D 01.2020 released with the KCGS and a new responsive design

Today, the first version of the P&D portal (01.2020) this year was released with one brand new set of kinase inhibitors, Kinase Chemogenomic Set (KCGS), several updated compound sets (also with new chemical probes from opnMe portal and Gray Laboratory Probes) and a brand new responsive design.

The Kinase Chemogenomic Set (KCGS) is a result of a long term effort to create a high-quality diverse set of selective kinase inhibitors containing 187 inhibitors that primarily cover 215 human kinases (The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification). On P&D you can already find a preliminary KCGS from a paper published two years ago, Progress towards a public chemogenomic set for protein kinases and a call for contributions (2017), containing 297 inhibitors that were, at the time, meeting the criteria for the inclusion into KCGS. Surprisingly, the overlap between these two sets, the preliminary one and the final KCGS (1.0), is "only" 112 compounds.

From the last version, the P&D UI was greatly enhanced to be more friendly and usable also on smaller devices and is now much more responsive. But still, concerning the amount of data displayed for each compound, the portal aims mainly for its usage on a standard screen with at least full HD resolution.

 

 

Finally, the database dump with all new data is as always available in the Download section of the portal and can be freely used under the CC BY-SA 4.0 license.

We hope you find the new data and functionality useful, and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.   

Dec. 18, 2019
P&D 11.2019 released with GTOPDB 2019.5, Concise GTOPDB 2019/20 and a taxonomy from ChEMBL

Today, the last version of P&D this year (11.2019) was released with Guide To Pharmacology 2019.5Concise Guide To Pharmacology 2019/20, the organism taxonomy from ChEMBL and also slightly improved compound standardization workflow.

"The Concise Guide to PHARMACOLOGY 2019/20 (CGTOP) is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties."

Since CGTOP (as well as GTOPDB) is a high-quality expert-validated resource, we did not only add already second CGTOP compound set to our database (you can see the difference between CGTOP 2017/18 and 2019/20 here), but we also decided to add the CGTOP annotations for specified compound-target pairs in order to highlight this information. The designated targets of the CGTOP compounds are labeled by a small "thumbs up" icon that can be found next to the target name:

However, be aware that even though CGTOP is an expert validated resource, there are for example 34 compounds that can be also found among the Obsolete compounds. So, always try to validate your chemical tools by data from more than one resource.

Concerning the new functionality, we integrated the organism taxonomy from ChEMBL that can be now used to filter compounds based on their potency measured for whole organisms and their taxonomic class. For example, now, you can easily filter all approved drugs that have at least 1 micromolar potency for any virus or bacterium:

You can also use the taxonomy to browse through compounds in the Targets tab in the Compounds view:

From this version, we also improved our compound standardization workflow by extending the list of salts/solvents that are stripped from the original compounds, and mainly, added one more step which normalizes isotopic atoms to their default state. Mainly this step caused that the number of standardized/nonisomeric compounds decreased by more than 1000 compared to previous P&D versions. 

We hope you find new data and functionality useful, and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form

Oct. 10, 2019
P&D 09.2019 is out with a new compounds' hierarchy and GTOPDB 2019.4

After P&D 07.2019 with minor data update, we skipped ver. 08.2019, and yesterday, we released P&D 09.2019 with redesigned hierarchical compounds structure (original, standardized and nonisomeric), and brand new data from Guide to Pharmacology 2019.4 (as well as many updated compound sets).

Up to version 07.2019, there were two types of structures on P&D: original and standardized. Original compounds were/are compounds as they are extracted from their source (database, webpage, file) without any modifications (structures are only parsed and canonicalized). While standardized compounds, up-to-now, have been unsalted, neutralized (if possible), NONISOMERIC versions of the original compounds. From now on, the stereochemistry is preserved in standardized compounds, while new NONISOMERIC compound type is introduced which represents STANDARDIZED compounds with removed stereochemistry. Based on the compounds' hierarchy, any standardized compound represents one or more original compounds and any nonisomeric compound represents one or more standardized/original compounds. All data associated with compound/s on a lower hierarchical level are combined together on a higher level (e.g., all data associated with original compounds sharing the same standardized compound, are also associated with the standardized compound).

Currently, the STANDARDIZED compounds view is the DEFAULT view when browsing compounds' data, but it is always possible to switch between different compound types just by clicking on one of the compound type icons:

Also, all related compounds (based on the structure hierarchy) can be found in the Compound detail view in the Related compounds tab:

In the near future, we plan to expand the compounds' hierarchy even into lower levels of structural detail (scaffolds, generic scaffolds, etc.).

Please note that due to the changes in the compounds' hierarchy, our database structure has been significantly modified and therefore, the current database dump (P&D 09.2019, PostgreSQL dump) is not compatible with previous dumps.  

 

July 3, 2019
P&D 06.2019 with Obsolete compounds and new global potency filters was released!

Earlier today, we released a new version of P&D portal (06.2019) with updated database, integrated set of obsolete compounds, and two new global potency filters.

Concerning new compounds, we updated two of the high-quality probe sets, Open Science Probes and opnMe portal, as well as we integrated the new version of the Guide to Pharmacology database (2019.03). There is also one new commercial set of bioactive compounds from Enamine (Enamine BioReference Compounds) "containing over 2000 compounds with extensive target classes’ coverage and the broadest possible therapeutic areas applications – from CNS agents and anti-infectives to anticancer drugs and steroids."

We also added a whole new compound set of so-called obsolete/historic compounds (acquired from Chemical Probes.org portal) which we plan to extend in the future. "Compounds in this set are typically non-selective or not sufficiently potent compared with other available chemical probes to merit the probe designation." All compounds contained in this set are marked with a red chemical probe icon (see the picture below).

From this version of P&D, you can already use three special (global) filters based on compounds' promiscuity and potency. Some time ago, we already introduced the Number of targets filter which can used to filter promiscuous compounds, and now we add two new filters concerning their target and cell-based potency: Max potency and Max cell potency filters. Both of these filters take into account all activity data from biochemical/cell-based assays for a single compound and work with its highest values. So, you can, for example, use these filters to get all compounds with less than 5 associated targets with at least 10 nanomolar target and 10 micromolar cell-based potencies.

If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

June 10, 2019
P&D ver. 05.2019 with simplified filtering and redesigned target data is out!

At the end of last week, P&D ver. 05.2019 was released with updated as well as brand new compound sets, improved filtering functionality, and redesigned target data.

Besides updated compound sets (SGC ProbesCayman ChemicalMedChem ExpressPrestwick and the Spectrum/Microsource bioactive compound libraries), there are two new compound sets, one non-commercial, ZINC Tool Compounds (compounds recommended as the best orthogonal substances for phenotypic screens), and one commercial, AdooQ Bioactive Compound Library, which consists of inhibitors, chemical probes and reference compounds for various research fields.

In order to simplify even more the filtering process on P&D and to improve the user experience on touch devices, we changed the way how filters are invoked on P&D. Originally, a user had to hover over a term he/she wanted to use as a filter and then click on the filter icon that appeared next to it. From this version, the filters can be simply invoked by clicking/tapping on the term the user wants to filter.

Concerning the target data, we moved from a source-based view (where very often duplicated activities from different databases were displayed) to a reference-based view, where the final bioactivity is the median value of all distinct reference activity values. In case there is a difference in median values of data extracted from ChEMBL/BindingDB and GtoPDB values (where only min, max, and median values are published), the final value is the median of these values. In the target section, we preferably display the value for Human targets; in case there are none, the value for all other organisms merged together is displayed. All the original bioactivity values can still be revealed by clicking on the icon with the number of references. The change to the one value/target design also comes with a new, more compact design of the target data section with integrated activity-based bar-chart that should better visualize the selectivity among targets.

With the new version of P&D, also the new version of the PostgreSQL dump of our database can be downloaded from the Downloads section.

If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

May 3, 2019
P&D 04.2019 released with Bromodomains chemical toolbox and PostgreSQL dump

At the beginning of May, Probes & Drugs portal ver. 04.2019 was released with brand new (as well as updated) data and also with a PostgreSQL dump of our database available to download. 

First of all, we added the Bromodomains chemical toolbox extracted from the paper by Wu et al, A chemical toolbox for the study of bromodomains and epigenetic signaling. The toolbox contains a set of 25 chemical probes selective small molecule inhibitors, covering 29 human bromodomain targets. The selectivity of the probes was comprehensively evaluated using BROMOscan, demonstrating the utility of the set identifying roles of BRDs in cellular processes and potential translational applications.

 From this version now on, users can also download the PostgreSQL dump of a full P&D database. New versions of the dump will be always released monthly accompanying every new version of P&D.

If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

April 3, 2019
P&D 03.2019 released with ChEMBL 25, GTOPDB 2019.02, and brackets for filtering expressions

On the last day of March, we released a new version of P&D (03.2019) with a lot of new data and functionalities. First of all, the data were updated to the brand new versions of ChEMBL (ver. 25) and Guide to Pharmacology (ver. 2019.2) databases. With them, also the associated ChEMBL Approved Drugs and Guide to Pharmacology compound sets were updated to their latest versions. 

From ver. 03.2019, P&D no longer contains only binding data from biochemical assays for Human, Rat and Mouse targets, but potency data (pValues: pIC50, pEC50, pKi etc.) for all organisms from binding and functional assays for targets, cell-lines and also whole organisms. For cell-line and organism targets, you can find two new sections added to the compound representation, for the cell-based potency of ligands on a concrete target, the information was added to the target section (see the picture below).

In order to be able to ask even more complex questions than before, we introduce the possibility to use brackets in the filtering expressions. A bracket can be simply added by clicking on the small arrow icon below any filter (at least two filters have to be selected) which will invoke the bracket (see the picture below). This will cause that the filters after the bracket are applied again on the full database and are combined together with preceding filters based on a selected Boolean operator. Since the information about the brackets, as well as the information about all current filters, is propagated to the URL, the filtered compound set can be easily shared with anyone.

As an example, you can try to filter compounds that bind selectively either to Estrogen receptor alpha (ESR1) or beta (ESR2), but not to both of them (based on available data), so-called exclusive OR operation (XOR). You can do this using brackets and filter compounds for ESR1 OR ESR2, but NOT compounds for ESR1 AND ESR2. 

We hope you’ll find the new data and functionality useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

March 1, 2019
P&D 02.2019 was released with the Malaria and Pandemic Response box, and OSM compound set

On the last day of February, the new version of P&D 02.2019 was released with three new data sets: the Malaria boxPandemic response box, and Open Source Malaria compound set.

The Malaria Box contains 400 compounds and has been assembled by MMV in a bid to catalyse malaria and neglected disease drug discovery and research. All of the compounds have confirmed activity against the blood-stage of P. falciparum and are commercially available.

The Pandemic Response Box have been assembled by MMV and DNDi, in association with scientists from industry and academia, to foster new research into treatments for pandemic diseases. The box will provide the community with a set of 400 structurally diverse compounds for screening against infective and neglected diseases. These 400 compounds with diverse mechanisms of action have been selected by disease experts from a comprehensive list of antibacterial, antivirals or antifungal compounds. All of them are either already marketed or are in various phases of drug discovery or development.

The Open Source Malaria (OSM) compound set is a current set of 795 molecules from the OSM project. OSM is aimed at finding new medicines for malaria using open source principles, embodied in the 6 Laws of Open Research. At the moment the majority of work involves the synthesis of analogs of compounds identified by big pharma, with the aim of improving their potency while making the molecules more druggable, what is known as a hit-to-lead campaign.

We hope you’ll find the new data useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Feb. 1, 2019
P&D ver. 01.2019 with the Potency-Selectivity score and chemical space networks

Since there was only a minor data update in P&D 12.2018, we skipped right to the ver. 01.2019 in our news section, released on the last day of January. P&D ver. 01.2019 brings new features (potency-selectivity score, chemical space networks), UI improvements (activity values displayed with their associated references, updated compounds style) and also one new probe data set (Protein methyltransferases and epigenetic signaling toolbox).

One of the main new features is the Potency-Selectivity score calculated for all compound-target pairs that can be found next to the target name in the Compounds view. From there, the PS score can be also used as a filter in order to find not only potent but also selective compounds. Our PS score was highly inspired by the potency and selectivity scores used in Probe Miner (see also the paper by Antolin et al.) (you can also find the Probe Miner suitable probes set here at P&D) with its detailed description in the FAQs section (here).

New features were also added to the chemical space (CS) visualization, where we updated our visualization library called ChemSpace.js, and it is now able to display CS networks (you can read more about the CSN here in FAQ). For its high computational demands, CS networks can be displayed for sets up-to 1500 compounds. Upon that, we've also added the possibility to visualize compound sets using t-SNE (<1500 compounds) and UMAP (<10000 compounds) embeddings.

On the image below, you can see the CSN of the Estrogen receptors target class with similarity threshold set to 0.5 and max NN to 5.

Concerning the UI improvements, we've updated the style of a single compound representation in the Compounds view in order to improve the clarity of the view and separation of the compounds. For better data transparency, we've also made available all underlying activity values associated with their sources (publications, patents, etc.). These values can be accessed by clicking on the references icon associated with a particular compound-target pair (see the image below).

The new probe compound set, Protein methyltransferases and epigenetic signaling toolbox, was extracted from the paper by Scheer et al., A chemical biology toolbox to study protein methyltransferases and epigenetic signaling, and it contains 19 compounds (all of them were already in the P&D database).

"This chemical probe collection and associated data form a resource for the study of methylation-mediated signaling in epigenetics, inflammation and beyond."

We hope you’ll find the new data and functionality useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Dec. 4, 2018
P&D ver. 11.2018 with a new set from Ki Database is out!

On the last day of November, a new version of P&D (11.2018) was released with a few updated and one brand new compound set from the Ki Database with 3964 compounds.

The PDSP (Psychoactive Drug Screening Program) Ki database is a unique resource in the public domain which provides information on the abilities of drugs to interact with an expanding number of molecular targets. The Ki database serves as a data warehouse for published and internally-derived Ki, or affinity, values for a large number of drugs and drug candidates at an expanding number of G-protein coupled receptors, ion channels, transporters and enzymes.

We hope you’ll find the new data useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Oct. 31, 2018
P&D ver. 10.2018 with new compound sets and scaffolds

On Halloween, a new version (10.2018) of P&D portal is out with with two new compound sets and also some new functionality.

The first new compound set is a set of CDK inhibitors extracted from the CDKidb, database released as a part of paper about the selectivity of commonly used CDK inhibitors, How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases? by Jorda et al. You can also read a commentary by Derek Lowe at his In the pipeline blogCDK Inhibitors: Purchase With Caution.

The second new set is a set of probes extracted from the web pages of the Nathanael Gray Lab at the Dana-Farber Cancer Institute. You can already find a set of best-in-class Kinase inhibitors by the same group in our collection (originally published in Molecular Cell here and here).

Beside the new compound sets, we've updated the Probe Miner (suitable probes) setLINCS compound set  and also some commercial bioactive compound libraries.

Apart from the new data, there is also a new functionality enabeling to analyze the scaffold enrichment of filtered compounds on a lower level of detail. Concretely, there are two new types of less detailed scaffolds that can be used: 1) generic scaffold and 2) scaffold based on a generic compound structure. To get a generic structure of a compound, all atom types are converted to carbon atoms and all bond types are converted to single bonds. In case of the first scaffold type, the scaffold itself is converted to its generic form, in case of the second, the compound is first converted to its generic form and than its scaffold is extracted. You can see the difference between all three current scaffold types in the image below. You can display all three current types of scaffolds by clicking on the Set summary icon (the pie chart icon) and select the Scaffolds option from the menu (in the image below).

Oct. 1, 2018
P&D ver. 09.2018 released!

On the last day of September, the new version (09.2018) of P&D was released with both new and updated datasets.

From the updated datasets, we would like to highlight the new version of one of our main data sources, Guide to Pharmacology (ver. 2018.04), and also updated probe sets, SGC Probes and opnMe portal.

One new dataset, added to P&D portal, is Clinical kinase drugs compound set extracted from a publication by Klaeger et al., The target landscape of clinical kinase drugs. The publication describes "a comprehensive analysis of 243 kinase inhibitors that are either approved for use or in clinical trials. They provide an open-access resource of target summaries that could help researchers develop better drugs, understand how existing drugs work, and design more effective clinical trials."

We hope you’ll find the new data useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Aug. 31, 2018
P&D ver. 08.2018 with two new compound sets is out!

The new version (08.2018) of P&D is out with two new compound sets extracted from a publication by Moret et al. with title Cheminformatics tools for analyzing and designing optimized small molecule libraries (currently on bioArxiv).

Both of the new compound sets were generated using the LibraryR application freely available as a part of The Small Molecule Suite, developed by the Harvard Initiative in Therapeutic Sciences (HiTS).

First is the LSP-OptimalKinase library (Laboratory of Systems Pharmacology), an improved version of the LINCS kinase library, based on the analysis of six kinase inhibitor libraries. According to the authors of the paper the LSP-OptimalKinase library "outperforms all previous collections in terms of target coverage and compact size." You can try to compare the library with other kinase inhibitor libraries currently found in the P&D collection: GSK Published Kinase Inhibitor SetKinase Chemogenomic SetKinase Inhibitors (best-in-class) and PKIDB.

The second compound set is the LSP-MoA library (Laboratory of Systems Pharmacology) designed to target the 1852 members of the liganded genome that should be of general utility in semi-focused screening campaigns. 

We hope you’ll find the new data useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Aug. 1, 2018
P&D 07.2018 with a Probe Miner compound set is out!

On the last day of July, we rolled out a new version (07.2018) of the Probes & Drugs portal with brand new as well as updated data.

This month, one new compound set was added to our list, and it is a set of compounds extracted from Probe Miner. Probe miner is a portal in a way similar to P&D, but with a target-centric approach to data. For every ligand-target pair in Probe Miner, a specialized score assessing the probe-likeness of a compound is calculated based on data extracted from the ChEMBL database (currently, from ChEMBL ver. 23). You can read more about the portal and their approach in Objective, Quantitative, Data-Driven Assessment of Chemical Probes. For P&D Probe Miner set, only compounds labeled as suitable probes (probe-likeness score >= 0.5) were selected (more than 2600 compounds).

Since the number of probes on the P&D portal sky-rocketed to almost 4000 compounds, we felt there is a need to distinguish between compounds that were labeled as probes based on a rigorous experimental testing, and others labeled as such based on available public data and selected criteria (calculated probes). As a beginning, we started to highlight their appointed targets with different colors: for classic probes, the color remains the same (green), but for calculated probes, the targets are highlighted with an orange probe icon (see the image below). However, we will go further in the upcoming months.

 

July 1, 2018
P&D ver. 06.2018 was released!

On the last day of June, we released a new version of P&D, ver. 06.2018. In this update, we integrated data from a recently released version of Guide to Pharmacology (ver. 2018.03), also accompanied by the Concise Guide to Pharmacology 2017/2018 compound set (CGTP).

CGTP is a series of biennial publications which provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open-access knowledgebase of drug targets and their ligands.

Another new compound set is an up-to-date set of commercially available compounds from the Tocris  Bioscience (downloaded from PubChem).

We hope you’ll find the new data useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

June 3, 2018
P&D ver. 05.2018 is out with ChEMBL 24, GtoPDB 2018.02 and much more!

After a short maintenance, we are back online with a brand new version of P&D portal (05.2018) accompanied with new data as well as new features and software updates.

Besides updated data sets and the incorporation of data from recently released versions of ChEMBL (ver. 24) and Guide to Pharmacology (ver. 2018.02), we added one new probe compound set to our collection, compounds harvested from the opnMe portal. opnMe portal currently contains 22 probes, donated to the community by Boehringer Ingelheim, that can be ordered free of charge, in many cases also acommpanied by their control compounds.

As a part of this update, we also integrated new versions of two of our important software tools. First of all, we updated our chemical editor Ketcher to ver. 2.0, since we found out that the former version can cause some problems for certain combinations of OS and web browser. We are sorry for the inconvenience and we hope that from now on there will be no such problems.

Second updated tool is our library for the chemical space visualization, ChemSpace.js, which from the current version uses smilesDrawer library for the depiction of molecules.

One new P&D feature, that you may notice when performing a substructure search or filtering compounds by a structural alert (e.g., individual PAINS filter), is the highlighting of the substructure in matched compounds (see the picture below).

We hope you’ll find the new data and functions useful and if you have any suggestions for new functions or compound sets we could include in our database, please, let us know through the contact form.

April 30, 2018
Probes & Drugs ver. 04.2018 is out!

On the last day of April, the new version (04.2018) of the Probes and Drugs portal is here, this time with two new data sets (apart from the updated ones). 

The first compound set is a probe set harvested from the Open science probes portal. Probes on this portal, including all associated data, control compounds and recommendations, were donated by several pharmaceutical libraries to be freely used by the community (Donated chemical probes for open science).

The second new compound set is yet another set of protein kinase inhibitors, PKIDB, a monthly-updated database gathering approved PKIs as well as PKIs currently in clinical trials (PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials).

We hope you’ll find the new data sets useful. If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

March 31, 2018
Probes & Drugs ver. 03.2018 was released!

We made it, and on the last day of March, we release the third version (03.2018) of the Probes and Drugs portal this year. 

Besides updated compound sets (SGC Probes, Guide to Pharmacology 2018.1 etc.), we added one brand new data set, the Kinase chemogenomic set, that was extracted from the paper Progress towards a public chemogenomic set for protein kinases and a call for contributions. Concretely, only compounds that meet the criteria for KCGS inclusion were added to the set.

This month, we've also started with the direct annotation of probe-target pairs, i.e., in case, that a probe has an assigned target/targets in the data extracted from its source, this target is now highlighted by a small probe icon next to its name (see the example below for the probe I-BRD9 and its target BRD9). So far, probes from Chemical probes.org, SGC Probes and Tool compound set are annotated, more sets will come in the near future.

We hope you’ll find the new data useful. If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Feb. 27, 2018
Probes & Drugs ver. 02.2018 is out!

Besides updated data sets and fixed bugs, there is one new ontology in this month's update, the ChEMBL's Gene Ontology slim was added to our current target ontologies. 

A drug target slim: using gene ontology and gene ontology annotations to navigate protein-ligand target space in ChEMBL

"The ‘ChEMBL protein target slim’ provides a means of firstly describing the biology of protein drug targets and secondly allows users to easily establish a connection between biological and chemical information regarding drugs and drug targets..."

You can access the ontology either from the Targets tab in the Compounds section or you can search for single terms from the ontology through our text search field.

We hope you’ll find the new data useful. If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Jan. 31, 2018
First version of Probes & Drugs in 2018 is out!

On the last day of January, Probe & Drugs ver. 01.2018 was released. In this version of our portal, there is one new compound set and two new filter types.

The one new compound set is the CeMM library of unique drugs (CLOUD) that 'covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies' (A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor). Our set actually contains only the core 274 compounds (from the original 308 drugs, 34 STEAM drugs with unknown molecular target were excluded).

Concerning the new filter types, one of them is a Reference filter which is able to filter all compounds associated with a reference (i.e., publication, patent, etc.). This filter can be invoked by the filter icon next to a reference in the Targets & Pathways section of each compound, or through the search filed.

The second new filter type is so called special filter. We call it special because normally this type of filter is not available to be used in any database of bioactive compounds. There is currently only one special filter, Number of targets, but there are more to come. This filter is able to filter and sort compounds according to their promiscuity. It can be invoked through the search field or by the filter icon that appears when the mouse cursor is over the number of targets in the Targets & Pathways section. Using this filter, you can for example ask a question "How many approved drugs have more than 50 known targets?".

We hope you’ll find the new data and functionality useful. If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Dec. 21, 2017
Probes & Drugs ver. 12.2017 is out!

In the last update of Probes & Drugs this year, you can find two new data sets (besides the updated ones):

  1. DrugMatrix - "Comprehensive Rat Toxicogenomics Database and Analysis Tool"

  2. TargetMol - "Contains more than 3,470 small molecule compounds, pays more attention on their targets. All compounds have targets description, which is the key point to drug screening."

This month, we also extracted all references for our biactivity data from ChEMBL, Guide to pharmacology and BindingDB (DrugBank will come in a near future). Now, all these references can be easily accessed by clicking on the references icon in the header of a target in the Targets and pathways section of each compound.

We hope you’ll find the new data and functionality useful. If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Since the end of year is very near, we would also like to wish you a Merry Christmas, Happy New Year and lot of new Probes & Drugs in the year to come.

Nov. 29, 2017
Probes & Drugs ver. 11.2017 is out!

Probes & Drugs portal ver. 11.2017 is here with one brand new compound set and one new feature for the chemical space visualization.

The new compound set, Tool compound set, is a probe set published in Report and Application of a Tool Compound Data Set (J. Chem. Inf. Model.). This set consists mainly of compounds extracted from the ChEMBL database (based on stringent criteria for their potency, selectivity etc., for more details, see the paper) in combination with probes from the Chemical probes portal.

The new function of our chemical space visualization is the ability to use values associated with a filter (e.g., activities associated with a target filter) within the visualization. Anytime such filter is used, its values are automatically added as an attribute which can be accessed and used through the chemical space menu. As an example, in the picture below, you can see chemical space visualization based on the ligands of Androgen and Glucocorticoid receptor where the points are colored according to their activity on the Androgen receptor. The ones not associated with the filter are gray. 

Again, if you have any suggestions for new compound sets or new functions, or if you stumble on an error, please, let us know through the contact form.

Oct. 26, 2017
Probes & Drugs ver. 10.2017 is out!

For the Probes & Drugs portal ver. 10.2017, we prepared the integration of the BindingDB data and highly enriched the bioactivity data already found in our database. Apart from that, some of the compound sets underwent their monthly update together with the addition of the last two versions of the NIH Approved Oncology Drug set (ver. VII and VIII).

We hope you’ll find the new data useful and if you have any suggestions for new functions or if you stumble on an error, please, let us know through the contact form.

Sept. 28, 2017
Probes & Drugs ver. 09.2017 is out!

In this month's update you can find two new data sets (besides the updated ones):

  1. Drug Repurposing Hub - "Drug repurposing experiments are limited by the lack of comprehensive screening libraries. We introduce a best-in-class drug screening collection with more than 3,000 clinical drugs. The Repurposing Hub information resource contains extensive curated annotations for each drug, including details about commercial sources of all compounds. We invite you to explore the Hub information resource as a first step towards discovering new therapeutic applications for existing drugs."

  2. The Pathogen Box - "The Pathogen Box contains ~400 diverse, drug-like molecules active against neglected diseases of interest and is available free of charge."

We've also enriched our target information by incorporating the data (MOA) from DrugBank.

Finally, we've added one new function some of you asked us for: Custom set creation by matching to a supplied list/file of structures/names. So now, you can easily create custom sets by e.g., uploading your SDF file or by pasting of the list of names from an Excel file. You can try it here. The function is still in beta state, so don't hesitate to contact us in case you stumble on an error.

We hope you’ll find the new data and function useful. If you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

Aug. 26, 2017
Probes & Drugs ver. 08.2017 is out!

This month’s version is finally out with both updated and brand new data as well as new functions. If you are not here for the first time, you’ve probably noticed that we have updated our homepage and also set up the Probes & Drugs Twitter account (you can follow us here).

Besides updated data sets, we’ve added one new compound set, the Bioprocess diversity set, from a recent paper in Nature Chemical biology, Functional annotation of chemical libraries across diverse biological processes.

You can also use new functions that should help you to find and browse through the filters:

  1. You can list all filters by clicking on the List filters icon above the text search field. The filters are divided by their type and ordered by the number of compounds they represent.

  2. Since there can be really a lot of filters (hundreds, in some cases thousands) suggested by the autocomplete when using the text search field, you can now list the matched filters by pressing enter when no specific filter from the list is selected.

We hope you’ll find the new functions useful and if you have any suggestions for new functions or compound sets we could include to our database, please, let us know through the contact form.

July 28, 2017
Probes & Drugs portal in Nature Methods

We are excited to announce that the Probes & Drugs portal paper has just been published in the August issue of Nature Methods. Appart from the Correspondence itself, it also contains extensive Supplementary Notes with information about data processing, portal interface, data sources/tools and more. 

July 26, 2017
Probes & Drugs Portal official launch

As of the 26th July, the Probes and Drugs portal is officially released in order to be used by the research community. We hope it will give everoyne the opportunity to interactively explore the bioactive compound space in a way not achievable before. Have fun!