2D Similarity-based Cysteine Protease Focused Library

Cysteine proteases can be found in all living organisms. In addition to their basic functions of catabolism and protein processing, cysteine proteases have a variety of functions. To prevent unwanted protein degradation, like other proteolytic enzymes (serine, aspartate and metalloproteases), cysteine proteases are synthesized as inactive precursors (or zymogens). Cysteine protease zymogens contain a prodomain that block access of substrate to the active site. Targeting cysteine proteases prior to activation may prevent their involvement in various diseases: targeting mature domain interactions that are important for activation and targeting residues involved in pH sensing and activation. To prevent unwanted digestion, cysteine proteases are synthesized as zymogens and contain a pre-structural domain (regulatory) and a mature structural domain (catalytic). The pre-structural domain acts as an endogenous inhibitor of the mature enzyme. In order to activate the mature enzyme, the prodomain needs to be removed and this is achieved by different modes. Pro-mature domain interactions can be classified as protein-protein interactions (PPI) and can be targeted in a range of diseases. Thus, they are promising drug targets for various diseases.

BOC Sciences is capable of designing a cysteine protease screening set based on 2D similarity methods.

Figure 1. Inhibition of cysteine protease action on proteins. (Kunert, K, J.; et al. 2015)

2D Similarity-based Cysteine Protease Focused Library Design

BOC Sciences has developed this unique library by employing a 2D similarity approach to provide more than 3,700 drug-like screening compounds.

1. Firstly, we collect a reference set of 7,200 biologically active compounds from cysteine protease-related assays through various databases
2. Then, the BOC Sciences HTS compound collection is applied to search for compounds similar to the compounds from the reference database using the MDL public key
3. Finally, our teams can produce small-molecule analogs of known cysteine protease inhibitors with experimentally determined activity

Here are drug targets used for the 2D similarity-based cysteine protease focused library:

• Caspase-3 (Cysteine protease CPP32)
• Caspase-6 (apoptotic Ced-3/Ice cysteine protease)
• Cysteine protease ATG4B
• Legumain (Cysteine Protease 1)
• Cruzipain (Major cysteine proteinase)-Trypanosoma cruzi
• Cysteine protease falcipain 2 and 3-Plasmodium falciparum
• Trophozoite cysteine proteinase-Plasmodium falciparum

Figure 2. Proposed action of stress-induced cystatins. (Kunert, K, J.; et al. 2015)

2D Similarity-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 2D Similarity-based Cysteine Protease Focused Library design at competitive prices for global customers. Personalized and customized services of 2D Similarity-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!