cathepsin S | C1: Papain | IUPHAR Guide to IMMUNOPHARMACOLOGY

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cathepsin S

  Target has curated data in GtoImmuPdb

Target id: 2353

Nomenclature: cathepsin S

Family: C1: Papain

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 331 1q21 CTSS cathepsin S
Mouse - 340 3 F2.1 Ctss cathepsin S
Rat - 330 2q34 Ctss cathepsin S
Previous and Unofficial Names
Cat S
Database Links
Specialist databases
MEROPS C01.034 (Hs)
Other databases
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.22.27

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound (R)-26 [PMID: 22686657] Hs Inhibition 9.3 pKi 1
pKi 9.3 (Ki 5.5x10-10 M) [1]
petesicatib Hs Inhibition 10.0 pIC50 5
pIC50 10.0 (IC50 1x10-10 M) [5]
petesicatib Mm Inhibition 9.5 pIC50 5
pIC50 9.5 (IC50 3x10-10 M) [5]
LHVS Hs Inhibition 9.0 pIC50 4
pIC50 9.0 (IC50 1x10-9 M) [4]
odanacatib Hs Inhibition 7.2 pIC50 2
pIC50 7.2 (IC50 6x10-8 M) [2]
View species-specific inhibitor tables
Immunopharmacology Comments
Cathepsin S is expressed in the lysosome of antigen presenting cells (dendritic cells, B-cells and macrophages) where it processes the invariant chain-MHC-II complex (a chaperone protein that prevents premature peptide loading) inside antigen presenting cells and in this way controls antigen presentation. Due to this role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression [6]. This enzyme is also a central pathomechanism in autoimmune diseases. Consequently, cathepsin S inhibitors are being investigated for clinical efficacy in autoimmune conditions. Roche's cathepsin S inhibitor petesicatib (RO5459072 or RG7625) completed Phase 2 clinical evaluation in Sjögren's syndrome (NCT02701985) and Phase 1 in celiac disease (NCT02679014), but there are no active clinical trials registered with ClinicalTrials.gov.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0002224 toll-like receptor signaling pathway TAS
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 3 GO processes
GO:0019882 antigen processing and presentation TAS
GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II TAS
GO:0048002 antigen processing and presentation of peptide antigen IDA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response IEP
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response IEP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0002224 toll-like receptor signaling pathway TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0002224 toll-like receptor signaling pathway TAS
GO:0043312 neutrophil degranulation TAS
General Comments
Cathepsin S, is a lysosomal cysteine protease, whch plays an important role in antigen presentation. Selective cathepsin S inhibitors are being developed for their therapeutic potential in autoimmune disorders, atherosclerosis, osteoporosis, osteoarthritis and cancer [3].

References

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1. Frizler M, Schmitz J, Schulz-Fincke AC, Gütschow M. (2012) Selective nitrile inhibitors to modulate the proteolytic synergism of cathepsins S and F. J. Med. Chem., 55 (12): 5982-6. [PMID:22686657]

2. Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong le T, Falgueyret JP, Kimmel DB, Lamontagne S, Léger S, LeRiche T et al.. (2008) The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg. Med. Chem. Lett., 18 (3): 923-8. [PMID:18226527]

3. Lee-Dutra A, Wiener DK, Sun S. (2011) Cathepsin S inhibitors: 2004-2010. Expert Opin Ther Pat, 21 (3): 311-37. [PMID:21342054]

4. Méthot N, Rubin J, Guay D, Beaulieu C, Ethier D, Reddy TJ, Riendeau D, Percival MD. (2007) Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processing. J. Biol. Chem., 282 (29): 20836-46. [PMID:17535802]

5. Tato M, Kumar SV, Liu Y, Mulay SR, Moll S, Popper B, Eberhard JN, Thomasova D, Rufer AC, Gruner S et al.. (2017) Cathepsin S inhibition combines control of systemic and peripheral pathomechanisms of autoimmune tissue injury. Sci Rep, 7 (1): 2775. [PMID:28584258]

6. Thurmond RL, Sun S, Karlsson L, Edwards JP. (2005) Cathepsin S inhibitors as novel immunomodulators. Curr Opin Investig Drugs, 6 (5): 473-82. [PMID:15912960]

How to cite this page

C1: Papain: cathepsin S. Last modified on 19/03/2018. Accessed on 20/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2353.