Receptor-based Cysteine Protease Focused Library

Protein hydrolases are essential for a variety of biological processes from lower to higher organisms. Proteases can cut proteins into smaller fragments by catalyzing the hydrolysis of peptide bonds. Proteases are classified according to their catalytic sites and are divided into four major groups: cysteine proteases, serine proteases, aspartate proteases, and metalloproteases. Cysteine proteases, including histone B, H and L, are generally found in lysosomes and are mainly involved in cellular phagocytosis and the removal and digestion of intracellular excess material. In recent years, the role of Cathepsin K (CatK) has received increasing attention. The optimal pH of CatK isolated from normal tissues is acidic and inactive under neutral or alkaline conditions, but CatK is more active in tumor tissues under neutral or alkaline conditions, which seems to be more appropriate for metabolic disorders in malignant tumors. CatK is one of the most potent proteases in the lysosomal cysteine protease family, and its main function is to mediate bone resorption. Currently, CatK is one of the most attractive protease targets for anti-osteoporosis drug discovery and development. In addition, histoproteases and other cysteine proteases may become good targets for major diseases.

BOC Sciences can design a receptor-based cysteine protease focused library based on the docking-based virtual screening protocol.

Figure 1. Collagen structures and digestion by Cathepsin K (CatK). (Cla, B.; et al. 2019)

Receptor-based Cysteine Protease Focused Library Design

BOC Sciences has designed a proprietary screening set of over 1,200 drug-like screening compounds selected for potential cathepsin K inhibitory activity by performing a virtual molecular screening.

1. Firstly, molecules from a compound collection of validated selective cathepsin K protease inhibitors and our HTS compounds reported are pre-screened through an internal structural filter
2. Then, Glide from Schrödinger's software is employed to dock at the enzyme active site, binding ligands are extracted from the reference crystal structure using X-ray data including 2ATO, 1NLJ, 1VSN, 1YK8
3. In addition, we define a set of constraints to improve the quality of the docking results

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