Cysteine Protease Focused Library

Cysteine proteases are one of the most biologically important clusters of proteins involved in a variety of cellular pathways. They participate in multiple processes, among which there are immune invasion, parasite invasion, parasite egress, hydrolysis, extracellular matrix turnover, making them promising drug targets for various diseases (e.g., AIDS, cancer, cardiovascular and inflammatory diseases, thrombosis, respiratory disease, pancreatitis, and neurological disorders) [1-2].

Being divided into 14 superfamilies, they are structurally different, however, sharing a common mechanism of action. Their unique role in protein degradation determines a broad distribution of cysteine proteases. It also implies a variability of active sites, as a result of the target folding specificity.

A similarity search was used as the universal method to design this Screening Library of potential cysteine proteases inhibitors. A reference database over 7,200 biologically active compounds from assays related to cysteine proteases was compiled using the data available from patents and literature publications. The Life Chemicals HTS Compound Collection was searched for compounds similar to the compounds from the reference database using MDL public keys and the Tanimoto similarity more than 85 %. PAINS filters were not applied for this Library preparation as they would remove a substantial part of both reference molecules and analogous screening compounds due to the nature of cysteine protease-targeted drugs. Reactive compounds were removed with in-house MedChem filters.

In total, the Library comprises over 3,700 screening compounds with potential inhibitory activity against cysteine proteases were included in the Library (Fig. 2):

  • 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

The compound selection can be customized based on your requirements, cherry-picking is available. A preplated set based on this Screening Library is also offered. For more details, please, consult our Pre-plated Focused Libraries. Please, contact us at for any additional information and price quotations.

Figure 1. Neighbor-joining sequence clustering analysis of reference cysteine proteases.

Compound analogues from the Cysteine Protease Focused Library

Figure 2. Compound analogues from the Cysteine Protease Focused Library which are similar to known cysteine protease inhibitors.


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  2. Verma, S.; Dixit, R.; Pandey, K. C. Cysteine Proteases: Modes of Activation and Future Prospects as Pharmacological Targets. Front. Pharmacol., 25, 2016, 7 (APR), 107.
  3. Fournier J, Chen K, Mailyan AK, Jackson JJ, Buckman BO, Emayan K, Yuan S, Rajagopalan R, Misialek S, Adler M, Blaesse M, Griessner A, Zakarian A. Total Synthesis of Covalent Cysteine Protease Inhibitor N-Desmethyl Thalassospiramide C and Crystallographic Evidence for Its Mode of Action. Org Lett. 2019 Jan 18;21(2):508-512. doi: 10.1021/acs.orglett.8b03821.
  4. Costa TF, Lima AP. Natural cysteine protease inhibitors in protozoa: Fifteen years of the chagasin family. Biochimie. 2016 Mar;122:197-207. doi: 10.1016/j.biochi.2015.11.002.
  5. Rustgi S, Boex-Fontvieille E, Reinbothe C, von Wettstein D, Reinbothe S. The complex world of plant protease inhibitors: Insights into a Kunitz-type cysteine protease inhibitor of Arabidopsis thaliana. Commun Integr Biol. 2017 Dec 14;11(1):e1368599. doi: 10.1080/19420889.2017.1368599.
  6. Lee H, Shin EA, Lee JH, Ahn D, Kim CG, Kim JH, Kim SH. Caspase inhibitors: a review of recently patented compounds (2013-2015). Expert Opin Ther Pat. 2018 Jan;28(1):47-59. doi: 10.1080/13543776.2017.1378426.


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