Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF2LRI)

• DTT Name: Cathepsin B (CTSB)
• Synonyms: Ctsb; Cathepsins B; Cathepsin-B; Cathepsin B1; CPSB; APPS; APP secretase
• Gene Name: CTSB
• DTT Type: Preclinical target; [1]
• BioChemical Class: Peptidase
• UniProt ID: CATB_HUMAN
• TTD ID: T61746
• EC Number: EC 3.4.22.1
• Sequence:
  MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCG
  TFLGGPKPPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDR
  ICIHTNAHVSVEVSAEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYESHVGCR
  PYSIPPCEHHVNGSRPPCTGEGDTPKCSKICEPGYSPTYKQDKHYGYNSYSVSNSEKDIM
  AEIYKNGPVEGAFSVYSDFLLYKSGVYQHVTGEMMGGHAIRILGWGVENGTPYWLVANSW
  NTDWGDNGFFKILRGQDHCGIESEVVAGIPRTDQYWEKI
• 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.
• KEGG Pathway:
  Lysosome (hsa04142)
  Antigen processing and presentation (hsa04612)
• Reactome Pathway:
  Trafficking and processing of endosomal TLR (R-HSA-1679131)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  MHC class II antigen presentation (R-HSA-2132295)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DTT

10 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dimethoxybenzylidene-2-thio-imidazole-4-one derivative 1	DMZ4B3W	Cerebral ischemia	8B11	Patented	[1]
PMID27998201-Compound-11	DMTV5NU	Metastatic cancer	2D50-2E2Z	Patented	[1]
PMID27998201-Compound-12	DM8QZNC	Bone cancer	2B5Z	Patented	[1]
PMID27998201-Compound-13	DMZHIM8	Hepatic fibrosis	DB93.0	Patented	[1]
PMID27998201-Compound-17	DMAZVHJ	Hair loss	ED70	Patented	[1]
PMID27998201-Compound-2	DMMAE3C	Alzheimer disease	8A20	Patented	[1]
PMID27998201-Compound-22	DMS9QA7	Alzheimer disease	8A20	Patented	[1]
PMID27998201-Compound-24	DM25BNZ	Glioma	2A00.0	Patented	[1]
PMID27998201-Compound-5	DMVZ0ND	Chronic obstructive pulmonary disease	CA22	Patented	[1]
PMID27998201-Compound-9	DM1JOZN	Rheumatoid arthritis	FA20	Patented	[1]

5 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CA-074Me	DMVN3FU	Cardiac arrest	MC82	Preclinical	[2]
L-006235-1	DMMEH12	Osteoarthritis	FA00-FA05	Preclinical	[3]
SD1002	DMLAF6C	Alzheimer disease	8A20	Preclinical	[4]
SD1003	DM29BW1	Alzheimer disease	8A20	Preclinical	[4]
Z-Phe-Ala-diazomethylketone	DMX23CZ	Alzheimer disease	8A20	Preclinical	[4]

30 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate	DMICUQK	Discovery agent	N.A.	Investigative	[5]
1-(phenyl(p-tolyl)methylene)thiosemicarbazide	DMU10CY	Discovery agent	N.A.	Investigative	[6]
2-Aminoethanimidic Acid	DM2OE1W	Discovery agent	N.A.	Investigative	[7]
2-Pyridinethiol	DMVAQOZ	Discovery agent	N.A.	Investigative	[8]
3-Amino-4-Oxybenzyl-2-Butanone	DM5Z0O6	Discovery agent	N.A.	Investigative	[7]
3-Methylphenylalanine	DMQOI5X	Discovery agent	N.A.	Investigative	[7]
Ac-hPhe-Leu-Ala-LeuVSMe	DMU7SBD	Discovery agent	N.A.	Investigative	[9]
Ac-hPhe-Leu-Phe-LeuVSMe	DMMDJPC	Discovery agent	N.A.	Investigative	[9]
Bis(3-bromophenyl)(4-hydroxy)thiosemicarbazone	DM784AU	Discovery agent	N.A.	Investigative	[10]
Cbz-Ile-Leu-Ala-LeuVSMe	DMBFLHD	Discovery agent	N.A.	Investigative	[9]
Cbz-Ile-t-ButylhomoGlu-Ala-LeuVSMe	DMNKC9J	Discovery agent	N.A.	Investigative	[9]
Diphenylacetic Acid	DMP6IHR	Discovery agent	N.A.	Investigative	[7]
GNF-PF-5434	DMP9AIH	Discovery agent	N.A.	Investigative	[11]
Gold trichloride sodium chloride	DMS97A1	Discovery agent	N.A.	Investigative	[12]
L-873724	DMUP516	Asthma	CA23	Investigative	[13]
PTosyl-Glu(OtBu)-Ala-LeuVSMe	DMPEVQT	Discovery agent	N.A.	Investigative	[9]
Z-Ala-Leu-His-Agly-Ile-Val-OMe	DMMP0DT	Discovery agent	N.A.	Investigative	[14]
Z-Ala-Leu-lle-Agly-Ile-Val-NHBzl	DM7IGRT	Discovery agent	N.A.	Investigative	[14]
Z-Ala-Leu-lle-Agly-Ile-Val-OMe	DMVEUOL	Discovery agent	N.A.	Investigative	[14]
Z-Ala-Leu-Nal-Agly-Ile-Val-OMe	DM3209T	Discovery agent	N.A.	Investigative	[14]
Z-Ala-Leu-Phe-Agly-Ile-Val-OMe	DML16BT	Discovery agent	N.A.	Investigative	[14]
Z-Ala-Leu-Tyr(Me)-Agly-Ile-Val-OMe	DMIB5O3	Discovery agent	N.A.	Investigative	[14]
Z-Arg-Leu-Val-Agly-Ala-Gly-NH2	DM69FKN	Discovery agent	N.A.	Investigative	[14]
Z-Arg-Leu-Val-Agly-Ile-Val-OMe	DM9SXMB	Discovery agent	N.A.	Investigative	[14]
Z-Arg-Leu-Val-Agly-Ile-Val-Trp-NH2	DMZDGJO	Discovery agent	N.A.	Investigative	[14]
Z-Arg-Leu-Val-Agly-Ileu-Val-OMe	DMT0UZ1	Discovery agent	N.A.	Investigative	[14]
Z-Arg-Leu-Val-Agly-Trp-Val-Ala-NH2	DMM5O2V	Discovery agent	N.A.	Investigative	[14]
Z-Arg-Leu-Val-Agly-Val-Ala-NH2	DMTWNH7	Discovery agent	N.A.	Investigative	[14]
Z-leu-Val-Agly-Val-OBzl	DM6OGR9	Discovery agent	N.A.	Investigative	[14]
[(3-Bromophenyl)-p-tolyl-ketone]thiosemicarbazone	DMZG7TH	Discovery agent	N.A.	Investigative	[15]

References

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• [2] CA-074Me inhibits Cathepsin-B and alleviates fibrosis after myocardial infarction. Panminerva Med. 2019 Sep 24.
• [3] 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.
• [4] Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948.
• [5] Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83.
• [6] Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett. 2008 May 1;18(9):2883-5.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [8] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [9] 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.
• [10] Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6610-5.
• [11] Substrate optimization for monitoring cathepsin C activity in live cells. Bioorg Med Chem. 2009 Feb 1;17(3):1064-70.
• [12] 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.
• [13] The identification of potent, selective, and bioavailable cathepsin S inhibitors. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33.
• [14] 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.
• [15] Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1415-9.