Skip to main content

Drug safety information: Boxed warnings and Withdrawn drugs

Updated drug safety information is available (as of ChEMBL 28) for drugs with boxed warnings and for withdrawn drugs. 

Boxed warnings (also know as black box warnings) are provided on medicinal product labels for FDA approved drugs if the medicinal product can cause severe or life-threatening side effects. They are free text descriptions, enclosed within a black box, hence the name! For example, Oxaprozin is used to treat osteoarthritis but carries a boxed warning.

Our recent work has classified the type of adverse effect described in boxed warnings on a per drug basis. For medicinal products that contain one active pharmaceutical ingredient, a boxed warning can be directly linked to a drug. Therefore, toxicity class(es) have been assigned to approved drugs with boxed warning information described on medicinal product labels (e.g. Cardiotoxicity, Hepatotoxicity etc). Clickable links to examples of medicinal product labels with boxed warning text descriptions have been retained to allow database users to drill down through the information “audit trail” to examine the source information. Further details are available from Hunter et al., 2021

As part of this effort, source references for previously curated withdrawn drugs have also been publicly exposed, ie drugs that have been approved but subsequently withdrawn from one or more markets of the world for safety reasons. See our blog on Withdrawn Drugs.

All safety information can be accessed in the ChEMBL web interface via the Drugs view (which is grouped by parent compound) or via the Compound view (for either view, filter on the left hand side by 'withdrawn flag' or 'black box warning'). For an individual drug, detailed drug warning information and source references are available on the Compound Report Card, e.g. Tolcapone, CHEMBL1324, is approved to treat Parkinson's Disease but carries a warning of Hepatotoxicity:
  





Programatic access is also available via our new Drug_Warning API endpoint, e.g. a search for hepatotoxic drugs (either withdrawn or those with a boxed warning) could apply this syntax: 
https://www.ebi.ac.uk/chembl/api/data/drug_warning.json?warning_class=Hepatotoxicity

The drug safety information allows drugs that cause similarly reported toxicities to be easily grouped, analyzed, and visualized. The ChEMBL resource contains a wide range of bioactivity data types, from early “Discovery” stage preclinical data for individual compounds through to postclinical data on marketed drugs; the inclusion of the drug safety information within this framework can support a wide range of safety-related drug discovery questions. The drug safety information will be updated in future database releases. 

This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116030. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. 




Comments

Popular posts from this blog

Sequence similarity searches in ChEMBL

  The ChEMBL database contains bioactivity data that links compounds to their biological targets.  Most ChEMBL targets are proteins (~ 70% in version 27) and these are mapped to their UniProt accessions.   On the ChEMBL interface, searches can be performed with either protein names or accessions...but did you know that protein similarity searches are also possible? Here’s an example using human Phospholipase DDHD2 , a target not found in ChEMBL.       1.       On the ChEMBL interface , click 'Enter a Sequence:     2.       Input the FASTA sequence corresponding to human  Phospholipase DDHD2  and click 'Search in ChEMBL':  3.      Review the BLAST results, select targets of interest and browse bioactivity data: The BLAST  search identifies the mouse  Phospholipase DDHD2   homologue alongside a small number of bioactivity data points and active compounds . ChEMBL's sequence search feature is currently only available through the interface. However, sequence data for prote

ChEMBL 29 Released

  We are pleased to announce the release of ChEMBL 29. This version of the database, prepared on 01/07/2021 contains: 2,703,543 compound records 2,105,464 compounds (of which 2,084,724 have mol files) 18,635,916 activities 1,383,553 assays 14,554 targets 81,544 documents Data can be downloaded from the ChEMBL FTP site:   https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_29 .  Please see ChEMBL_29 release notes for full details of all changes in this release: https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_29/chembl_29_release_notes.txt New Deposited Datasets EUbOPEN Chemogenomic Library (src_id = 55, ChEMBL Document IDs CHEMBL4649982-CHEMBL4649998): The EUbOPEN consortium is an Innovative Medicines Initiative (IMI) funded project to enable and unlock biology in the open. The aims of the project are to assemble an open access chemogenomic library comprising about 5,000 well annotated compounds covering roughly 1,000 different proteins, to synthesiz

Julia meets RDKit

Julia is a young programming language that is getting some traction in the scientific community. It is a dynamically typed, memory safe and high performance JIT compiled language that was designed to replace languages such as Matlab, R and Python. We've been keeping an an eye on it for a while but we were missing something... yes, RDKit! Fortunately, Greg very recently added the MinimalLib CFFI interface to the RDKit repertoire. This is nothing else than a C API that makes it very easy to call RDKit from almost any programming language. More information about the MinimalLib is available directly from the source . The existence of this MinimalLib CFFI interface meant that we no longer had an excuse to not give it a go! First, we added a BinaryBuilder recipe for building RDKit's MinimalLib into Julia's Yggdrasil repository (thanks Mosè for reviewing!). The recipe builds and automatically uploads the library to Julia's general package registry. The build currently targe

ChEMBL 28 Released!

  We are pleased to announce the release of ChEMBL_28. This version of the database, prepared on 15/01/2021 contains: * 2,680,904 compound records * 2,086,898 compounds (of which 2,066,376 have mol files) * 17,276,334 activities * 1,358,549 assays * 14,347 targets * 80,480 documents Data can be downloaded from the ChEMBL FTP site:   https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_28 . Please see ChEMBL_26 release notes for full details of all changes in this release:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_28/chembl_28_release_notes.txt DATA CHANGES SINCE THE LAST RELEASE This release includes several new deposited data sets: Donated Chemical Probes data from SGC Frankfurt (src_id = 54) SARS-CoV-2 screening data from the Fraunhofer Institute (src_id = 52) Antimicrobial screening data sets from CO-ADD (src_id = 40) Plasmodium screening data from the UCSD Winzeler lab (src_id = 51) MMV pathogen box screening data (src_id = 34) Curated data

Identifying relevant compounds in patents

  As you may know, patents can be inherently noisy documents which can make it challenging to extract drug discovery information from them, such as the key targets or compounds being claimed. There are many reasons for this, ranging from deliberate obfuscation through to the long and detailed nature of the documents. For example, a typical small molecule patent may contain extensive background information relating to the target biology and disease area, chemical synthesis information, biological assay protocols and pharmacological measurements (which may refer to endogenous substances, existing therapies, reaction intermediates, reagents and reference compounds), in addition to description of the claimed compounds themselves.  The SureChEMBL system extracts this chemical information from patent documents through recognition of chemical names, conversion of images and extraction of attached files, and allows patents to be searched for chemical structures of interest. However, the curren