Currently, serine proteases are one of the most biologically important protein families and they have been demonstrated to play multiple roles in various diseases. In addition to their primary function of coordinating digestion, serine proteases are also involved in other processes such as inflammation, blood clotting, and the immune system expression in prokaryotes and eukaryotes. It is found that serine proteases consist of two unique β-barrel structural domains that converge at the catalytic active site. Serine proteases can therefore be further classified according to their substrate specificity as trypsin-like (positively charged residues Lys /Arg), elastase-like (small hydrophobic residues Ala, Val, Gly) or chymotrypsin-like (large hydrophobic residues Phe/Tyr/Trp).
BOC Sciences has designed two dedicated sets of potential serine protease modulator to facilitate high-throughput screening of small molecules for serine protease-related drug discovery programs.
Figure 1. One strategy to inhibit protease activity by targeting the autolysis loop (colored in magenta). (Longguang, J.; et al. 2021)
Serine Protease Screening Library Design
BOC Sciences has utilized different techniques to design two libraries to screen potential serine protease modulators to facilitate small molecule high-throughput screening for protease-based drug discovery programs.
A 2D fingerprint similarity search method is applied to provide a selection of over 4,400 drug-like screening compounds that are small-molecule analogs of known serine protease inhibitors with experimentally determined activity. Moreover, the MDL public key and a Tanimoto similarity cutoff of 85% are employed to perform the filtering.
Our teams design a docking-based virtual screening protocol to identify and select potential serine protease inhibitors. BOC Sciences has prepared a novel manual assessment of receptor-ligand complexes and compound diversity to further narrow the screening set down to nearly 6,500 compounds. In addition, bacterial proteases that belong to the family S2A are quite similar in the regions of the active site residues to follow the same patterns. A partial list of proteases known to belong to the trypsin family is shown below:
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Figure 2. Proposed pro-oncogenic signaling pathways for different serine protease. (Tanabe, M.; List, K. 2016)
Serine Protease Screening Library Characteristics
- High diversity over the screening set: mean Tanimoto > 0.85
- Favorable physicochemical parameters and solubility requirements
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Bioactivity and safety confirmed by preclinical studies and clinical trials
- Structural diversity, medicinal activity, and cellular penetration
- Structural document, IC50, and other chemical and biological data are provided
- All compounds are continually updated
- Compound cherry-picking service is provided
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of Serine Protease Screening Library design at competitive prices for global customers. Personalized and customized services of Serine Protease Screening Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
References
- Longguang, J.; et al. A general strategy to inhibit serine protease by targeting its autolysis loop. The FASEB Journal. 2021. 35(2).
- Tanabe, M.; List, K. The Role of Type II Transmembrane Serine Protease Mediated Signaling in Cancer. Febs Journal. 2016. 284(10): 1421-1436
