## 4 Examples of Commercial Targeted Libraries
### Protease-Inhibitor-Focused Libraries  
Proteases are enzymes which break down proteins by the hydrolysis of peptide bonds and are involved in various processes, making them potential targets for drug design [87]. Based on the mechanism of catalysis, several types exist, with the most common being the serine and cysteine proteases [87]. When inspecting such libraries, it is important to note that the design of covalent inhibitors requires different CADD approaches than for the design of non-covalent inhibitors [88]. The TargetMol molecular library consists of 295 protease inhibitors and includes known actives against serine, cysteine, aspartic and other proteases. All compounds have a confirmed IC\({}_{50}\), although the exact tests used and references to the primary literature are neither discussed nor disclosed. All compounds are NMR and HPLC validated and have their biological activity described. The ApexBio library of protease inhibitors was constructed by cherry picking of compounds that are associated with different proteases. The total number of compounds (825), the quality control certificates and a chart of composition are provided, but little or no information is given about properties such as IC\({}_{50}\) values or references to filtering protocols. Otava offers no less than 19 different protease libraries, with little information on their design provided. Where this information is available, virtual screening approaches were used to construct the library. These include receptor-based approaches such as pharmacophore and docking protocols to obtain molecules with the predicted activity. No evidence of activity or assays against the selected target is given. The Enamine compound supplier provides a protease-focused library with 117 known protease inhibitors. All of the available compounds were NMR and HPLC validated to ensure quality. The Selleckchem protease-focused library contains 319 small molecules with NMR and HPLC analytical data. It was constructed by manually searching the available literature on protease inhibitors, but no exact literature references are provided. The library has over 140 citations in scientific articles at the time of the writing of this paper. The number of compounds per target molecule is depicted with a graphical representation on the webpage. The compound supplier Asinex also offers protease-focused libraries of compounds, but with no exact details on the design provided to the customer. There are three libraries: the protease library, with 6640 compounds selected from their Signature and BioDesign Libraries; the Protease inhibitors library, with 80 compounds obtained by using screening against a panel of proteases; and the inhibitor library, with 80 compounds obtained by using pharmacophore modeling. Figure 8: Compound (relative) retention after post-filtering for REOS, PAINS, Aggregators and the Lipinski rule of 5 (one rule break allowed) on protein–protein-interaction-inhibitor-targeted libraries. ChemDiv offers two libraries: the cysteine and serine protease inhibitors databases. The databases were assembled by using in silico methods and created by following two key approaches: by comparing structural similarity of molecules in the ChemDiv database to molecules with known activity against proteases and by selecting molecules with structural motifs commonly represented in peptidomimetics, with little additional design information provided to the customer. The LifeChemicals protease inhibitor library comprises cystein, serine, aspartic and metallo protease inhibitor libraries. Both ligand- and receptor-based approaches were applied in the construction of this library. The molecules in the library are based on 80,000 reference molecules with a proven activity that were retrieved from the ChEMBL database. Some compounds from the LifeChemicals library were added based on the 2D fingerprint similarity with a Tanimoto comparison cutoff of 85% for serine and cystein proteases and of 75% for metalloproteases.