Target Information
| Target General Information | Top | |||||
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| Target ID |
T41141
(Former ID: TTDR01031)
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| Target Name |
Cathepsin L (CTSL)
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| Synonyms |
Major excreted protein; MEP; Cathepsin L1; CTSL1
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| Gene Name |
CTSL
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Coagulation defect [ICD-11: 3B10] | |||||
| Function |
Important for the overall degradation of proteins in lysosomes.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.22.15
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| Sequence |
MNPTLILAAFCLGIASATLTFDHSLEAQWTKWKAMHNRLYGMNEEGWRRAVWEKNMKMIE
LHNQEYREGKHSFTMAMNAFGDMTSEEFRQVMNGFQNRKPRKGKVFQEPLFYEAPRSVDW REKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPQGNEGCNG GLMDYAFQYVQDNGGLDSEESYPYEATEESCKYNPKYSVANDTGFVDIPKQEKALMKAVA TVGPISVAIDAGHESFLFYKEGIYFEPDCSSEDMDHGVLVVGYGFESTESDNNKYWLVKN SWGEEWGMGGYVKMAKDRRNHCGIASAASYPTV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T48K08 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | KGP94 | Drug Info | Clinical trial | Coagulation defect | [2] | |
| Patented Agent(s) | [+] 8 Patented Agents | + | ||||
| 1 | Phenylalanine derivative 1 | Drug Info | Patented | Glioma | [3] | |
| 2 | PMID27998201-Compound-1 | Drug Info | Patented | Coronavirus infection | [3] | |
| 3 | PMID27998201-Compound-12 | Drug Info | Patented | Cancer related pain | [3] | |
| 4 | PMID27998201-Compound-17 | Drug Info | Patented | Hair loss | [3] | |
| 5 | PMID27998201-Compound-19 | Drug Info | Patented | Solid tumour/cancer | [3] | |
| 6 | PMID27998201-Compound-5 | Drug Info | Patented | Cirrhosis | [3] | |
| 7 | PMID27998201-Compound-7 | Drug Info | Patented | Abdominal aortic aneurysm | [3] | |
| 8 | PMID27998201-Compound-9 | Drug Info | Patented | Rheumatoid arthritis | [3] | |
| Preclinical Drug(s) | [+] 6 Preclinical Drugs | + | ||||
| 1 | CLIK-148 | Drug Info | Preclinical | Rheumatoid arthritis | [4] | |
| 2 | CLIK-181 | Drug Info | Preclinical | Rheumatoid arthritis | [4] | |
| 3 | L-006235-1 | Drug Info | Preclinical | Osteoarthritis | [5] | |
| 4 | SD1002 | Drug Info | Preclinical | Alzheimer disease | [4] | |
| 5 | SD1003 | Drug Info | Preclinical | Alzheimer disease | [4] | |
| 6 | Z-Phe-Ala-diazomethylketone | Drug Info | Preclinical | Alzheimer disease | [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 45 Inhibitor drugs | + | ||||
| 1 | KGP94 | Drug Info | [1] | |||
| 2 | Phenylalanine derivative 1 | Drug Info | [3] | |||
| 3 | PMID25399719-Compound-17 | Drug Info | [6] | |||
| 4 | PMID27998201-Compound-1 | Drug Info | [3] | |||
| 5 | PMID27998201-Compound-12 | Drug Info | [3] | |||
| 6 | PMID27998201-Compound-17 | Drug Info | [3] | |||
| 7 | PMID27998201-Compound-19 | Drug Info | [3] | |||
| 8 | PMID27998201-Compound-5 | Drug Info | [3] | |||
| 9 | PMID27998201-Compound-6 | Drug Info | [3] | |||
| 10 | PMID27998201-Compound-7 | Drug Info | [3] | |||
| 11 | PMID27998201-Compound-9 | Drug Info | [3] | |||
| 12 | CLIK-148 | Drug Info | [7] | |||
| 13 | CLIK-181 | Drug Info | [4] | |||
| 14 | L-006235-1 | Drug Info | [8] | |||
| 15 | SD1002 | Drug Info | [4] | |||
| 16 | SD1003 | Drug Info | [4] | |||
| 17 | Z-Phe-Ala-diazomethylketone | Drug Info | [4] | |||
| 18 | (3-Bromobenzoylpyridine)thiosemicarbazone | Drug Info | [1] | |||
| 19 | (S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate | Drug Info | [9] | |||
| 20 | (S)-tert-butyl 1-oxohexan-2-ylcarbamate | Drug Info | [9] | |||
| 21 | 1-(1,3-diphenylpropylidene)thiosemicarbazide | Drug Info | [10] | |||
| 22 | 1-(phenyl(p-tolyl)methylene)thiosemicarbazide | Drug Info | [10] | |||
| 23 | 6-(benzylamino)-9-butyl-9H-purine-2-carbonitrile | Drug Info | [11] | |||
| 24 | 9-benzyl-6-(benzylamino)-9H-purine-2-carbonitrile | Drug Info | [11] | |||
| 25 | BIPHENYL-4-YL-ACETALDEHYDE | Drug Info | [12] | |||
| 26 | Bis(3-bromophenyl)(4-hydroxy)thiosemicarbazone | Drug Info | [1] | |||
| 27 | Bis(3-bromophenyl)(5-hydroxy)thiosemicarbazone | Drug Info | [1] | |||
| 28 | Bis(3-Fluorophenyl)-ketone]thiosemicarbazone | Drug Info | [13] | |||
| 29 | CAA0225 | Drug Info | [14] | |||
| 30 | Cysteinesulfonic Acid | Drug Info | [15] | |||
| 31 | L-873724 | Drug Info | [16] | |||
| 32 | N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile | Drug Info | [17] | |||
| 33 | N-(benzyloxycarbonyl)-leucyl-glycine-nitrile | Drug Info | [17] | |||
| 34 | N-(tert-butoxycarbonyl)-isoleucyl-glycine-nitrile | Drug Info | [17] | |||
| 35 | N-(tert-butoxycarbonyl)-leucyl-glycine-nitrile | Drug Info | [17] | |||
| 36 | N-(tert-butoxycarbonyl)-methionyl-glycine-nitrile | Drug Info | [17] | |||
| 37 | N-(tert-butoxycarbonyl)-norleucyl-glycine-nitrile | Drug Info | [17] | |||
| 38 | N-(tert-butoxycarbonyl)-tyrosyl-glycine-nitrile | Drug Info | [17] | |||
| 39 | N-(tert-butoxycarbonyl)-valyl-glycine-nitrile | Drug Info | [17] | |||
| 40 | N-acetyl-phenylalanyl-glycine-nitrile | Drug Info | [17] | |||
| 41 | N-benzoyl-phenylalanyl-glycine-nitrile | Drug Info | [17] | |||
| 42 | Peptide alpha-keto-beta-aldehyde-based inhibitors | Drug Info | [18] | |||
| 43 | [(3-Bromophenyl)-m-tolyl-ketone]thiosemicarbazone | Drug Info | [13] | |||
| 44 | [(3-Bromophenyl)-p-tolyl-ketone]thiosemicarbazone | Drug Info | [13] | |||
| 45 | [2-Phenylacetophenone]thiosemicarbazone | Drug Info | [1] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Lysosome | |||||
| 2 | Phagosome | |||||
| 3 | Antigen processing and presentation | |||||
| 4 | Proteoglycans in cancer | |||||
| 5 | Rheumatoid arthritis | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | IL4 Signaling Pathway | |||||
| 2 | TGF_beta_Receptor Signaling Pathway | |||||
| Reactome | [+] 6 Reactome Pathways | + | ||||
| 1 | Endosomal/Vacuolar pathway | |||||
| 2 | Collagen degradation | |||||
| 3 | Degradation of the extracellular matrix | |||||
| 4 | Trafficking and processing of endosomal TLR | |||||
| 5 | Assembly of collagen fibrils and other multimeric structures | |||||
| 6 | MHC class II antigen presentation | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Primary Focal Segmental Glomerulosclerosis FSGS | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6610-5. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6533). | |||||
| REF 3 | Cathepsin B and L inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2017 Jun;27(6):643-656. | |||||
| REF 4 | Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948. | |||||
| REF 5 | Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. Bone. 2012 Jun;50(6):1250-9. | |||||
| REF 6 | An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31. | |||||
| REF 7 | Structure-based development of specific inhibitors for individual cathepsins and their medical applications. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(2):29-39. | |||||
| REF 8 | Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional se... J Med Chem. 2005 Dec 1;48(24):7535-43. | |||||
| REF 9 | Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83. | |||||
| REF 10 | Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett. 2008 May 1;18(9):2883-5. | |||||
| REF 11 | Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. J Med Chem. 2008 Feb 14;51(3):545-52. | |||||
| REF 12 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 13 | Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1415-9. | |||||
| REF 14 | Characterization of CAA0225, a novel inhibitor specific for cathepsin L, as a probe for autophagic proteolysis. Biol Pharm Bull. 2009 Mar;32(3):475-9. | |||||
| REF 15 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 16 | The identification of potent, selective, and bioavailable cathepsin S inhibitors. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33. | |||||
| REF 17 | Interaction of papain-like cysteine proteases with dipeptide-derived nitriles. J Med Chem. 2005 Dec 1;48(24):7688-707. | |||||
| REF 18 | Synthesis and kinetic evaluation of peptide alpha-keto-beta-aldehyde-based inhibitors of trypsin-like serine proteases. J Pharm Pharmacol. 2001 Apr;53(4):473-80. | |||||
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