Receptor-based Serine Protease Focused Library

Trypsin and chymotrypsin-like serine proteases from family S1 constitute the largest protease groups in humans. Membrane-anchored serine proteases have an emerging role in cancer with important physiological tasks. Despite the high diversity of all family members, they share the tandem b-barrel architecture of the chymotrypsin-fold in the catalytic domain, conferred by the great variation of the eight surface loops around the active site, active-site-containing domain found in the trypsin family members. Bacterial proteases belonging to the S2A family are very similar in the region of the active site residues to follow the same pattern.

BOC Sciences has designed a proprietary screening set of over 6,500 structurally-diverse small-molecule screening compounds picked out by virtual molecular screening.

Figure 1. Serine proteases mechanisms of action. (Coppini, R.; et al. 2019)

Receptor-based Serine Protease Focused Library Design

1. Firstly, crucial target information can be obtained based on X-ray data of known complexes with chymotrypsin and other serine protease inhibitors
2. Then, A Schrödinger software is applied to establish a virtual screening workflow in which binding ligands are extracted from the reference crystal structures
3. Our teams use an internal structural filter to obtain molecules from the reference set of different selective serine protease inhibitors and BOC Sciences HTS compounds collection which are then docked in the active site of the enzyme
4. Finally, a dedicated screening set will be selected for each target protein, and each docked target is indicated for each screening compound

• Trypsin

Multi-domain trypsin-like proteases are key members in the tightly controlled blood coagulation and complement systems, as well as in related proteases secreted from various immune cells. The catalytic activity of serine proteases from the trypsin family is provided by a charge relay system that involves the hydrogen bonding of aspartate residues to histidine, which in turn is hydrogen bonded to serine

• Chymotrypsin

Chymotrypsin is a protein hydrolase secreted by the pancreas, capable of cleaving almost any protein. Chymotrypsin has similar effects as trypsin, but with higher catabolic capacity, lower toxicity and fewer adverse effects than trypsin. Chymotrypsin is widely used for the treatment of sprains, otitis media, rhinitis, sinusitis, pharyngitis, and lung abscess. BOC Sciences has developed several chymotrypsin inhibitors to treat surgical inflammation, wounds, hematomas and abscesses

• Subtilisin-like serine protease

Currently, subtilisin-like serine protease remains the most essential, important and widely used enzyme species. Subtilisin-like serine protease is able to catalyze the hydrolysis of proteins into amino acids. Since the high-resolution structure of subtilisin-like protease is well known, and there are suitable cloning approach, expression systems and accurate methods for quantitative analysis of the catalytic activity of the enzyme. Subtilisin-like serine protease is therefore a suitable target for protein engineering and new drug research and development

Figure 2. Direct anticoagulants may be thought as indirect PAR inhibitors. (Coppini, R.; et al. 2019)

• Thrombin

Thrombin is a trypsin-like allosteric serine protease that plays a role in the coagulation chain reaction. Thrombin serine proteases play a key role in many physiological and pathological processes, such as involvement in protein catabolism, coagulation, cell growth and migration, tissue development, tumor growth and metastasis, etc. BOC Sciences has established a library of thrombin serine protease inhibitors

• Factor Xa

Factor Xa is a serine protease that possesses the ability to break peptide bonds in large proteins to make them into small molecules. In mammals, serine proteases play an important role, especially in digestion, coagulation and the complement system. Its activation is achieved through changes in a group of amino acid residues in the active center

• Elastase

Elastases are simple digestive proteases in the intestine, and belong to the classes of serine proteases, cysteine proteases and metalloproteases. Mammalian elastases are found mainly in the pancreas and phagocytes. Among the non-mammalian elastases, a variety of serine elastases are present. Elastases play a pathological role in emphysema, cystic fibrosis, infection, inflammation and atherosclerosis

Figure 3. Pharmacological strategies to control hyperacoagulability and heart inflammation. (Coppini, R.; et al. 2019)

Receptor-based Serine Protease Focused 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 Receptor-based Serine Protease Focused Library design at competitive prices for global customers. Personalized and customized services of Receptor-based Serine Protease Focused 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!