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cathepsin K

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Target not currently curated in GtoImmuPdb

Target id: 2350

Nomenclature: cathepsin K

Family: C1: Papain

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 329 1q21.3 CTSK cathepsin K
Mouse - 329 3 40.74 cM Ctsk cathepsin K
Rat - 329 2q34 Ctsk cathepsin K
Previous and Unofficial Names Click here for help
Cat K | CTSO | CTSO2 | Ms10q | PKND | PYCD
Database Links Click here for help
Specialist databases
MEROPS C01.036 (Hs)
Other databases
Alphafold P43235 (Hs), P55097 (Mm), O35186 (Rn)
BRENDA 3.4.22.38
ChEMBL Target CHEMBL268 (Hs), CHEMBL1075277 (Mm), CHEMBL3034 (Rn)
Ensembl Gene ENSG00000143387 (Hs), ENSMUSG00000028111 (Mm), ENSRNOG00000021155 (Rn)
Entrez Gene 1513 (Hs), 13038 (Mm), 29175 (Rn)
Human Protein Atlas ENSG00000143387 (Hs)
KEGG Enzyme 3.4.22.38
KEGG Gene hsa:1513 (Hs), mmu:13038 (Mm), rno:29175 (Rn)
OMIM 601105 (Hs)
Orphanet ORPHA120897 (Hs)
Pharos P43235 (Hs)
RefSeq Nucleotide NM_000396 (Hs), NM_007802 (Mm), NM_031560 (Rn)
RefSeq Protein NP_000387 (Hs), NP_031828 (Mm), NP_113748 (Rn)
UniProtKB P43235 (Hs), P55097 (Mm), O35186 (Rn)
Wikipedia CTSK (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.22.38

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
relacatib Small molecule or natural product Primary target of this compound Hs Inhibition 9.4 pKi 2
⤷ pKi 9.4 (Ki 4.1x10-10 M) [2]
compound 1b [PMID: 16290936] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pKi 1
⤷ pKi 8.7 (Ki 1.8x10-9 M) [1]
K777 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pKi 7
⤷ pKi 6.4 (Ki 4x10-7 M) [7]
calpeptin Peptide Click here for species-specific activity table Hs Inhibition 10.0 pIC50 3
⤷ pIC50 10.0 (IC50 1.1x10-10 M) [3]
odanacatib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.7 pIC50 5
⤷ pIC50 9.7 (IC50 2x10-10 M) [5]
L873724 Small molecule or natural product Primary target of this compound Hs Inhibition 9.7 pIC50 4
⤷ pIC50 9.7 (IC50 2x10-10 M) [4]
compound 23 [PMID: 35944849] Small molecule or natural product Hs Inhibition 9.3 pIC50 6
⤷ pIC50 9.3 (IC50 5x10-10 M) [6]
balicatib Small molecule or natural product Primary target of this compound Hs Inhibition 8.9 pIC50 2
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [2]
GC-376 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 8
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [8]
UAWJ9-36-3 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 8
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [8]
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Immune regulation
Immuno Process:  Inflammation
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ctsk+|Ctsktm1(cre)Ska|Esr1tm1Mma Ctsktm1(cre)Ska/Ctsk+,Esr1tm1Mma/Esr1tm1Mma
involves: 129S2/SvPas * C57BL/6 * SJL		 MGI:107823  MGI:1352467  MP:0002896 abnormal bone mineralization PMID: 17803905 
Ctsk+|Ctsktm1(cre)Ska|Esr1tm1Mma Ctsktm1(cre)Ska/Ctsk+,Esr1tm1Mma/Esr1tm1Mma
involves: 129S2/SvPas * C57BL/6 * SJL		 MGI:107823  MGI:1352467  MP:0001541 abnormal osteoclast physiology PMID: 17803905 
Ctsk+|Ctsktm1(cre)Ska|Esr1tm1Mma Ctsktm1(cre)Ska/Ctsk+,Esr1tm1Mma/Esr1tm1Mma
involves: 129S2/SvPas * C57BL/6 * SJL		 MGI:107823  MGI:1352467  MP:0010121 decreased bone mineral density PMID: 17803905 
Ctsk+|Ctsktm1(cre)Ska|Esr1tm1Mma Ctsktm1(cre)Ska/Ctsk+,Esr1tm1Mma/Esr1tm1Mma
involves: 129S2/SvPas * C57BL/6 * SJL		 MGI:107823  MGI:1352467  MP:0004992 increased bone resorption PMID: 17803905 
Ctsk+|Ctsktm1(cre)Ska|Esr1tm1Mma Ctsktm1(cre)Ska/Ctsk+,Esr1tm1Mma/Esr1tm1Mma
involves: 129S2/SvPas * C57BL/6 * SJL		 MGI:107823  MGI:1352467  MP:0004984 increased osteoclast cell number PMID: 17803905 
Ctsk+|Ctsktm1(cre)Ska|Esr1tm1Mma Ctsktm1(cre)Ska/Ctsk+,Esr1tm1Mma/Esr1tm1Mma
involves: 129S2/SvPas * C57BL/6 * SJL		 MGI:107823  MGI:1352467  MP:0000066 osteoporosis PMID: 17803905 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Pycnodysostosis
Disease Ontology: DOID:0080038
OMIM: 265800
Orphanet: ORPHA763

References

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1. Adkison KK, Barrett DG, Deaton DN, Gampe RT, Hassell AM, Long ST, McFadyen RB, Miller AB, Miller LR, Payne JA et al.. (2006) Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?. Bioorg Med Chem Lett, 16 (4): 978-83. [PMID:16290936]

2. Allen JG, Fotsch C, Babij P. (2010) Emerging targets in osteoporosis disease modification. J Med Chem, 53 (11): 4332-53. [PMID:20218623]

3. Catalano JG, Deaton DN, Long ST, McFadyen RB, Miller LR, Payne JA, Wells-Knecht KJ, Wright LL. (2004) Design of small molecule ketoamide-based inhibitors of cathepsin K. Bioorg Med Chem Lett, 14 (3): 719-22. [PMID:14741275]

4. Desmarais S, Massé F, Percival MD. (2009) Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools. Biol Chem, 390 (9): 941-8. [PMID:19453281]

5. 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]

6. Ginnetti AT, Paone DV, Nanda KK, Li J, Busuek M, Johnson SA, Lu J, Soisson SM, Robinson R, Fisher J et al.. (2022) Lead optimization of cathepsin K inhibitors for the treatment of Osteoarthritis. Bioorg Med Chem Lett, 74: 128927. [PMID:35944849]

7. Mellott DM, Tseng CT, Drelich A, Fajtová P, Chenna BC, Kostomiris DH, Hsu J, Zhu J, Taylor ZW, Kocurek KI et al.. (2021) A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells. ACS Chem Biol, 16 (4): 642-650. [PMID:33787221]

8. Xia Z, Sacco M, Hu Y, Ma C, Meng X, Zhang F, Szeto T, Xiang Y, Chen Y, Wang J. (2021) Rational Design of Hybrid SARS-CoV-2 Main Protease Inhibitors Guided by the Superimposed Cocrystal Structures with the Peptidomimetic Inhibitors GC-376, Telaprevir, and Boceprevir. ACS Pharmacol Transl Sci, 4 (4): 1408-1421. [PMID:34414360]

How to cite this page

C1: Papain: cathepsin K. Last modified on 03/10/2022. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2350.