Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T61746
(Former ID: TTDR00886)
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| Target Name |
Cathepsin B (CTSB)
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| Synonyms |
Ctsb; Cathepsins B; Cathepsin-B; Cathepsin B1; CPSB; APPS; APP secretase
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| Gene Name |
CTSB
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| Target Type |
Preclinical target
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[1] | ||||
| Disease | [+] 21 Target-related Diseases | + | ||||
| 1 | Alopecia [ICD-11: ED70] | |||||
| 2 | Bone cancer [ICD-11: 2B5Z] | |||||
| 3 | Brain cancer [ICD-11: 2A00] | |||||
| 4 | Cerebral ischaemic stroke [ICD-11: 8B11] | |||||
| 5 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
| 6 | Chronic pain [ICD-11: MG30] | |||||
| 7 | Digestive system disease [ICD-11: DE2Z] | |||||
| 8 | Hepatic fibrosis/cirrhosis [ICD-11: DB93] | |||||
| 9 | Meningioma [ICD-11: 2A01] | |||||
| 10 | Metastatic tumour [ICD-11: 2D50-2E2Z] | |||||
| 11 | Multiple sclerosis [ICD-11: 8A40] | |||||
| 12 | Neurodegenerative disorder [ICD-11: 8A20-8A23] | |||||
| 13 | Pancreatitis [ICD-11: DC31-DC34] | |||||
| 14 | Psoriasis [ICD-11: EA90] | |||||
| 15 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| 16 | Alzheimer disease [ICD-11: 8A20] | |||||
| 17 | Cardiac arrest [ICD-11: MC82] | |||||
| 18 | Cystic fibrosis [ICD-11: CA25] | |||||
| 19 | Idiopathic interstitial pneumonitis [ICD-11: CB03] | |||||
| 20 | Osteoarthritis [ICD-11: FA00-FA05] | |||||
| 21 | Asthma [ICD-11: CA23] | |||||
| Function |
Cleaves matrix extracellular phosphoglycoprotein MEPE. Has also been implicated in tumor invasion and metastasis. Thiol protease which is believed to participate in intracellular degradation and turnover of proteins.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.22.1
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| Sequence |
MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCG
TFLGGPKPPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDR ICIHTNAHVSVEVSAEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYESHVGCR PYSIPPCEHHVNGSRPPCTGEGDTPKCSKICEPGYSPTYKQDKHYGYNSYSVSNSEKDIM AEIYKNGPVEGAFSVYSDFLLYKSGVYQHVTGEMMGGHAIRILGWGVENGTPYWLVANSW NTDWGDNGFFKILRGQDHCGIESEVVAGIPRTDQYWEKI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T90ZKN | |||||
| Drugs and Modes of Action | Top | |||||
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| Patented Agent(s) | [+] 10 Patented Agents | + | ||||
| 1 | Dimethoxybenzylidene-2-thio-imidazole-4-one derivative 1 | Drug Info | Patented | Cerebral ischemia | [1] | |
| 2 | PMID27998201-Compound-11 | Drug Info | Patented | Metastatic cancer | [1] | |
| 3 | PMID27998201-Compound-12 | Drug Info | Patented | Cancer related pain | [1] | |
| 4 | PMID27998201-Compound-13 | Drug Info | Patented | Hepatic fibrosis | [1] | |
| 5 | PMID27998201-Compound-17 | Drug Info | Patented | Hair loss | [1] | |
| 6 | PMID27998201-Compound-2 | Drug Info | Patented | Alzheimer disease | [1] | |
| 7 | PMID27998201-Compound-22 | Drug Info | Patented | Neurodegenerative disorder | [1] | |
| 8 | PMID27998201-Compound-24 | Drug Info | Patented | Meningioma tumour | [1] | |
| 9 | PMID27998201-Compound-5 | Drug Info | Patented | Cirrhosis | [1] | |
| 10 | PMID27998201-Compound-9 | Drug Info | Patented | Rheumatoid arthritis | [1] | |
| Preclinical Drug(s) | [+] 5 Preclinical Drugs | + | ||||
| 1 | CA-074Me | Drug Info | Preclinical | Cardiac arrest | [2] | |
| 2 | L-006235-1 | Drug Info | Preclinical | Osteoarthritis | [3] | |
| 3 | SD1002 | Drug Info | Preclinical | Alzheimer disease | [4] | |
| 4 | SD1003 | Drug Info | Preclinical | Alzheimer disease | [4] | |
| 5 | Z-Phe-Ala-diazomethylketone | Drug Info | Preclinical | Alzheimer disease | [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 45 Inhibitor drugs | + | ||||
| 1 | Dimethoxybenzylidene-2-thio-imidazole-4-one derivative 1 | Drug Info | [1] | |||
| 2 | PMID27998201-Compound-11 | Drug Info | [1] | |||
| 3 | PMID27998201-Compound-12 | Drug Info | [1] | |||
| 4 | PMID27998201-Compound-13 | Drug Info | [1] | |||
| 5 | PMID27998201-Compound-17 | Drug Info | [1] | |||
| 6 | PMID27998201-Compound-2 | Drug Info | [1] | |||
| 7 | PMID27998201-Compound-22 | Drug Info | [1] | |||
| 8 | PMID27998201-Compound-24 | Drug Info | [1] | |||
| 9 | PMID27998201-Compound-5 | Drug Info | [1] | |||
| 10 | PMID27998201-Compound-9 | Drug Info | [1] | |||
| 11 | CA-074Me | Drug Info | [5] | |||
| 12 | L-006235-1 | Drug Info | [6] | |||
| 13 | SD1002 | Drug Info | [4] | |||
| 14 | SD1003 | Drug Info | [4] | |||
| 15 | Z-Phe-Ala-diazomethylketone | Drug Info | [4] | |||
| 16 | (S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate | Drug Info | [7] | |||
| 17 | 1-(phenyl(p-tolyl)methylene)thiosemicarbazide | Drug Info | [8] | |||
| 18 | 2-Aminoethanimidic Acid | Drug Info | [9] | |||
| 19 | 2-Pyridinethiol | Drug Info | [10] | |||
| 20 | 3-Amino-4-Oxybenzyl-2-Butanone | Drug Info | [9] | |||
| 21 | 3-Methylphenylalanine | Drug Info | [9] | |||
| 22 | Ac-hPhe-Leu-Ala-LeuVSMe | Drug Info | [11] | |||
| 23 | Ac-hPhe-Leu-Phe-LeuVSMe | Drug Info | [11] | |||
| 24 | Bis(3-bromophenyl)(4-hydroxy)thiosemicarbazone | Drug Info | [12] | |||
| 25 | Cbz-Ile-Leu-Ala-LeuVSMe | Drug Info | [11] | |||
| 26 | Cbz-Ile-t-ButylhomoGlu-Ala-LeuVSMe | Drug Info | [11] | |||
| 27 | Diphenylacetic Acid | Drug Info | [9] | |||
| 28 | GNF-PF-5434 | Drug Info | [13] | |||
| 29 | Gold trichloride sodium chloride | Drug Info | [14] | |||
| 30 | L-873724 | Drug Info | [15] | |||
| 31 | PTosyl-Glu(OtBu)-Ala-LeuVSMe | Drug Info | [11] | |||
| 32 | Z-Ala-Leu-His-Agly-Ile-Val-OMe | Drug Info | [16] | |||
| 33 | Z-Ala-Leu-lle-Agly-Ile-Val-NHBzl | Drug Info | [16] | |||
| 34 | Z-Ala-Leu-lle-Agly-Ile-Val-OMe | Drug Info | [16] | |||
| 35 | Z-Ala-Leu-Nal-Agly-Ile-Val-OMe | Drug Info | [16] | |||
| 36 | Z-Ala-Leu-Phe-Agly-Ile-Val-OMe | Drug Info | [16] | |||
| 37 | Z-Ala-Leu-Tyr(Me)-Agly-Ile-Val-OMe | Drug Info | [16] | |||
| 38 | Z-Arg-Leu-Val-Agly-Ala-Gly-NH2 | Drug Info | [16] | |||
| 39 | Z-Arg-Leu-Val-Agly-Ile-Val-OMe | Drug Info | [16] | |||
| 40 | Z-Arg-Leu-Val-Agly-Ile-Val-Trp-NH2 | Drug Info | [16] | |||
| 41 | Z-Arg-Leu-Val-Agly-Ileu-Val-OMe | Drug Info | [16] | |||
| 42 | Z-Arg-Leu-Val-Agly-Trp-Val-Ala-NH2 | Drug Info | [16] | |||
| 43 | Z-Arg-Leu-Val-Agly-Val-Ala-NH2 | Drug Info | [16] | |||
| 44 | Z-leu-Val-Agly-Val-OBzl | Drug Info | [16] | |||
| 45 | [(3-Bromophenyl)-p-tolyl-ketone]thiosemicarbazone | Drug Info | [17] | |||
| 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 | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Lysosome | |||||
| 2 | Antigen processing and presentation | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| 2 | IL2 Signaling Pathway | |||||
| Reactome | [+] 4 Reactome Pathways | + | ||||
| 1 | Collagen degradation | |||||
| 2 | Trafficking and processing of endosomal TLR | |||||
| 3 | Assembly of collagen fibrils and other multimeric structures | |||||
| 4 | MHC class II antigen presentation | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Cathepsin B and L inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2017 Jun;27(6):643-656. | |||||
| REF 2 | Drugs and Targets in Fibrosis. Front Pharmacol. 2017 Nov 23;8:855. | |||||
| REF 3 | 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 4 | Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948. | |||||
| REF 5 | CA-074Me inhibits Cathepsin-B and alleviates fibrosis after myocardial infarction. Panminerva Med. 2019 Sep 24. | |||||
| REF 6 | 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 7 | Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83. | |||||
| REF 8 | Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett. 2008 May 1;18(9):2883-5. | |||||
| REF 9 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 10 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 11 | Optimization of subsite binding to the beta5 subunit of the human 20S proteasome using vinyl sulfones and 2-keto-1,3,4-oxadiazoles: syntheses and c... J Med Chem. 2006 May 18;49(10):2953-68. | |||||
| REF 12 | 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 13 | Substrate optimization for monitoring cathepsin C activity in live cells. Bioorg Med Chem. 2009 Feb 1;17(3):1064-70. | |||||
| REF 14 | Inhibition of lysosomal cysteine proteases by chrysotherapeutic compounds: a possible mechanism for the antiarthritic activity of Au(I). Bioorg Med Chem Lett. 2004 Oct 18;14(20):5113-6. | |||||
| REF 15 | The identification of potent, selective, and bioavailable cathepsin S inhibitors. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33. | |||||
| REF 16 | Azapeptides structurally based upon inhibitory sites of cystatins as potent and selective inhibitors of cysteine proteases. J Med Chem. 2002 Sep 12;45(19):4202-11. | |||||
| REF 17 | Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1415-9. | |||||
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