Proteases are one of the largest potential drug target enzyme families. Nowadays, 647 human gene products containing protease sequences and mutant proteases have been identified successfully. Moreover, there are many proteases have been identified in viruses, bacteria and parasites, which are also potential drug targets. Over the past few decades, there has been a growing awareness that proteasomes can be used as potential drug targets in certain cancer diseases. Inhibition of protease activity regulates physiological functions, and enhances the beneficial effects of peptides either by reducing the formation of unwanted peptide mediators or by preventing their catabolism.
BOC Sciences has designed a series of protease libraries capable of performing rapid discovery and design of novel protease inhibitors, providing additional opportunities to target new chemical spaces and achieve selectivity profiles.
Protease Screening Library Design
BOC Sciences is able to prepare a collection of drug-like screening compounds with potential protease inhibitory activity to facilitate protease-based drug discovery. Our teams have used multiple computer-assisted methods, particularly docking-based virtual screening of the HTS compound collection for the identification of protease active sites.
Aspartate proteases are one of the four classes of proteolytic enzymes that cleave other proteins into smaller fragments. BOC Sciences has employed a 2D fingerprint similarity search methodology to design its proprietary aspartate protease focused library for protease-based drug discovery programs. The library includes more than 1,400 drug-like screening compounds that are small molecule analogs of known aspartate protease inhibitors with experimentally determined activity
A variety of clinical studies have shown that increased levels of cellular apoptosis and caspase activity are frequently observed at sites of cellular injury in both acute and chronic states. Therefore, inhibition of caspase activity may reduce cell death and provide a promising beneficial therapeutic effect for tissue injury. Aiming to identify potential caspase inhibitors and apoptosis-related compounds, we are committed to establishing a cysteinase screening library using a docking-based virtual screening method
Targeted covalent inhibitors have the potential to be more potent than non-covalent analogs, and the focus of targeted covalent inhibitors design has been directed towards targeting noncatalytic cysteine residues, such as cysteine proteases and protein kinases. Cysteine has great potential due to its relatively low protein abundance in proteins and its high nucleophilicity. In addition, the thiolate form of cysteine can form covalent bonds with covalent warheads spanning a wide range of reactivities
Figure 1. Synthetic protease switches with tailored response functions and combinatorial 3-step assembly of a synthetic protease switch. (Alexander, G.; et al. 2020)
As one of the most important protein families, serine proteases have played multiple roles in different diseases such as cancer proliferation, auto-immune disoders and allergies. BOC Sciences has designed two dedicated serine protease screening libraries for drug discovery programs using 2D similarity search and receptor-based virtual screening, respectively
Caseinolytic protease is a key member of the mitochondrial protein quality control system. This serine protease enables to remove damaged or misfolded proteins in the mitochondrial matrix, making the inhibition of ClpP an effective therapeutic strategy for human acute myeloid leukemia. Our teams have combined two receptor-based approaches: pharmacophore screening and molecular docking to develop our ClpP-targeted library
Currently, KLK6 activity has been observed in many cancers and neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis. Therefore, small-molecule compounds that modulate Kallilrein 6 activity may have significant therapeutic potential, and we are capable of performing two receptor-based approaches: molecular docking and pharmacophore screening to provide a high-quality kallikrein 6 targeted library
Human preproteinase (hPreP, PITRM1) is a mitochondrial ATP-independent metalloproteinase. It can degrade toxic peptides, including mitochondrial presequences and β-amyloid. Clinical studies have shown that this enzyme is an attractive target for Alzheimer's disease drug design. Considering that, BOC Sciences can use two approaches to design this specific screening library to provide compounds with predicted hPreP activation activity
Figure 2. Allosteric proteases: switch-on configuration. (Alexander, G.; et al. 2020)
Diverse studies have shown that an over-active renin-angiotensin-aldosterone system leads to vasoconstriction and retention of sodium and water, which will further cause hypertension. Renin (REN, HNFJ2) is an aspartate protease (also known as angiotensinogenase) that regulates the body's mean arterial blood pressure. With the aim of provide a perfect basis for a hypertension-related drug discovery program, we design a strategy of combining both ligand-based and receptor-based virtual screening methods to synthesize a renin targeted library
Cathepsin K is a lysosomal cysteine protease involved in bone remodeling and resorption. It plays an important role in osteoporosis and other bone-related pathologies, cancer, diabetes, obesity and atherosclerosis. BOC Sciences has used a receptor-based virtual screen to design a cathepsin K targeted library to explore cathepsin K inhibitors that show great potential in the treatment of such diseases
Protease Screening Library Characteristics
- 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
- All of these compounds with Tanimoto index ≥ 0.80
- 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 Protease Screening Library design at competitive prices for global customers. Personalized and customized services of 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!
Reference
- Alexander, G.; et al. iFLinkC: an iterative functional linker cloning strategy for the combinatorial assembly and recombination of linker peptides with functional domains. Nucleic Acids Research. 2020. 4(4).
