The concept of druggability is most often restricted to small molecules (low molecular weight organic substances)[1] but also has been extended to include biologic medical products such as therapeutic monoclonal antibodies.
If no known drugs bind to a target, then druggability is implied or predicted using different methods that rely on evolutionary relationships, 3D-structural properties or other descriptors.
[citation needed] This relies on the availability of experimentally determined 3D structures or high quality homology models.
A number of methods exist for this assessment of druggability but all of them consist of three main components:[5][6][7][8] Early work on introducing some of the parameters of structure-based druggability came from Abagyan and coworkers[9] and then Fesik and coworkers,[10] the latter by assessing the correlation of certain physicochemical parameters with hits from an NMR-based fragment screen.
A publicly available database of pre-calculated druggability assessments for all structural domains within the Protein Data Bank (PDB) is provided through the ChEMBL's DrugEBIlity portal.
[22][23][24] A potentially much larger percentage of proteins could be made druggable if protein–protein interactions could be disrupted by small molecules.
[27][28] Chemoproteomics techniques have recently expanded the scope of what is deemed a druggable target through the identification of covalently modifiable sites across the proteome.