Data for assessing tractability with small molecule, antibody, and other clinical modalities
To support target prioritisation, the Open Targets Platform includes tractability data that identifies key details, including if there is a binding site suitable for small molecule binding, an accessible epitope for antibody based therapy, relevant data for using Proteolysis Targeting Chimeras (PROTACs), or a compound in clinical trials with a modality other than small molecule or antibody.
The tractability data can assist in target prioritisation by identifying potential drug targets suitable for discovery pipelines and therapeutic modalities that are most likely to succeed. It also supports further investigation of targets for which there are no ligands or experimental structures or those targets outside a "druggable" target family but with strong genetic associations.
Our target tractability is based on a modified version of Approaches to target tractability assessment – a practical perspective and The PROTACtable genome and has workflows that generate tractability assessments for small molecule (SM), antibody (AB), Proteolysis Targeting Chimeras (PR), and other clinical (OC) modalities.
The tractability assessments displayed on the Platform's target profile pages is the result of an open-source computational pipeline that performs in silico tractability assessments with small molecule, antibody, PROTAC, and other clinical modality workflows.
Data sources used in the pipeline include UniProt, HPA, PDBe, DrugEBIlity, ChEMBL, Pfam, InterPro, Complex Portal, DrugBank, Gene Ontology, and BioModels.
Assessments common to all modalities, ingested from ChEMBL, are:
- Approved Drug: the target has clinical precedence with Phase IV drugs;
- Advanced Clinical: the target has clinical precedence with Phase II or III drugs;
- Phase 1 Clinical: the target has clinical precedence with Phase I drugs.
We also include additional assessments specific to each modality.
- UniProt Ubiquitination: Target tagged with the Uniprot keyword “Ubl conjugation [KW-0832]”, which indicates that the protein has a ubiquitination site, based on evidence from the literature (source: Uniprot)
Alternatively, you can also download the input TSV file with the per-target assessments via FTP. To access this file, visit our FTP site and click on the release version (e.g. 21.04), followed by "input", followed by "annotation-files". You can then download the
tractability_bucketsTSV file. Descriptions of the columns found in the input file can be found on the pipeline README.md file.