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cathepsin L

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Target id: 2351

Nomenclature: cathepsin L

Family: C1: Papain

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 333 9q21.33 CTSL cathepsin L
Mouse - 334 13 33.26 cM Ctsl cathepsin L
Previous and Unofficial Names Click here for help
nackt | nkt | cathepsin L1 | fs | furless | MEP | Cat L | p39 cysteine proteinase
Database Links Click here for help
Specialist databases
MEROPS C01.032 (Hs)
Other databases
Alphafold P07711 (Hs), P06797 (Mm)
BRENDA 3.4.22.15
ChEMBL Target CHEMBL3837 (Hs), CHEMBL5291 (Mm)
Ensembl Gene ENSG00000135047 (Hs), ENSMUSG00000021477 (Mm)
Entrez Gene 1514 (Hs), 13039 (Mm)
Human Protein Atlas ENSG00000135047 (Hs)
KEGG Enzyme 3.4.22.15
KEGG Gene hsa:1514 (Hs), mmu:13039 (Mm)
OMIM 116880 (Hs)
Pharos P07711 (Hs)
RefSeq Nucleotide NM_001912 (Hs), NM_145918 (Hs), NM_001257971 (Hs), NM_001257972 (Hs), NM_009984 (Mm)
RefSeq Protein NP_666023 (Hs), NP_001903 (Hs), NP_001244901 (Hs), NP_001244900 (Hs), NP_034114 (Mm)
UniProtKB P07711 (Hs), P06797 (Mm)
Wikipedia CTSL (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.22.15

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
MG-101 Peptide Ligand has a PDB structure Hs Inhibition 10.2 pKi 3
⤷ pKi 10.2 (Ki 6.4x10-11 M) [3]
VBY-825 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.6 pKi 2
⤷ pKi 9.6 (Ki 2.5x10-10 M) [2]
K11777 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pKi 5
⤷ pKi 7.3 (Ki 5x10-8 M) [5]
Mpro inhibitor 13b Small molecule or natural product Hs Inhibition 6.5 pKi 3
⤷ pKi 6.5 (Ki 2.93x10-7 M) [3]
D6-3 Small molecule or natural product Hs Inhibition 9.6 pIC50 1
⤷ pIC50 9.6 (IC50 2.7x10-10 M) [1]
CAA0225 Small molecule or natural product Ligand has a PDB structure Rn Inhibition 8.7 pIC50 8
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [8]
GC-376 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 4.4x10-9 M) [9]
LHVS Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 6
⤷ pIC50 8.1 (IC50 7x10-9 M) [6]
KGP94 Small molecule or natural product Primary target of this compound Hs Inhibition 6.9 pIC50 4
⤷ pIC50 6.9 (IC50 1.314x10-7 M) [4]
compound 4d [PMID: 38746883] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 7
⤷ pIC50 6.2 (IC50 7.01x10-7 M) [7]
UAWJ9-36-3 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pIC50 9
⤷ pIC50 5.7 (IC50 1.81x10-6 M) [9]
View species-specific inhibitor tables
Immunopharmacology Comments
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Cellular signalling
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Inflammation

References

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1. Deng W, Hu X, Tian X, Zhang Y, Shang W, Zhang L, Shang L. (2024) Peptidomimetic Analogues Act as Effective Inhibitors against SARS-CoV-2 by Blocking the Function of Cathepsin L. J Med Chem, 67 (19): 17124-17143. [PMID:39292661]

2. Elie BT, Gocheva V, Shree T, Dalrymple SA, Holsinger LJ, Joyce JA. (2010) Identification and pre-clinical testing of a reversible cathepsin protease inhibitor reveals anti-tumor efficacy in a pancreatic cancer model. Biochimie, 92 (11): 1618-24. [PMID:20447439]

3. Falke S, Lieske J, Herrmann A, Loboda J, Karničar K, Günther S, Reinke PYA, Ewert W, Usenik A, Lindič N et al.. (2024) Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors. J Med Chem, 67 (9): 7048-7067. [PMID:38630165]

4. Kumar GD, Chavarria GE, Charlton-Sevcik AK, Yoo GK, Song J, Strecker TE, Siim BG, Chaplin DJ, Trawick ML, Pinney KG. (2010) Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L. Bioorg Med Chem Lett, 20 (22): 6610-5. [PMID:20933415]

5. 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]

6. 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]

7. Previti S, Ettari R, Calcaterra E, Roggia M, Natale B, Weldert AC, Müller-Ruttloff C, Salisch F, Irto A, Cigala RM et al.. (2024) Identification of Dual Inhibitors Targeting Main Protease (Mpro) and Cathepsin L as Potential Anti-SARS-CoV-2 Agents. ACS Med Chem Lett, 15 (5): 602-609. [PMID:38746883]

8. Takahashi K, Ueno T, Tanida I, Minematsu-Ikeguchi N, Murata M, Kominami E. (2009) Characterization of CAA0225, a novel inhibitor specific for cathepsin L, as a probe for autophagic proteolysis. Biol Pharm Bull, 32 (3): 475-9. [PMID:19252298]

9. 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 L. Last modified on 21/10/2024. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2351.