Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT135K92)

• DOT Name: Di-N-acetylchitobiase (CTBS)
• Synonyms: EC 3.2.1.-
• Gene Name: CTBS
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Allergic rhinitis
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Carcinoma of liver and intrahepatic biliary tract
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Ulcerative colitis
  Urinary tract infection
  Amyotrophic lateral sclerosis
  Type-1/2 diabetes
  Aplasia cutis congenita
  Corpus callosum, agenesis of
• UniProt ID: DIAC_HUMAN
• EC Number: 3.2.1.-
• Pfam ID: PF00704
• Sequence:
  MSRPQLRRWRLVSSPPSGVPGLALLALLALLALRLAAGTDCPCPEPELCRPIRHHPDFEV
  FVFDVGQKTWKSYDWSQITTVATFGKYDSELMCYAHSKGARVVLKGDVSLKDIIDPAFRA
  SWIAQKLNLAKTQYMDGINIDIEQEVNCLSPEYDALTALVKETTDSFHREIEGSQVTFDV
  AWSPKNIDRRCYNYTGIADACDFLFVMSYDEQSQIWSECIAAANAPYNQTLTGYNDYIKM
  SINPKKLVMGVPWYGYDYTCLNLSEDHVCTIAKVPFRGAPCSDAAGRQVPYKTIMKQINS
  SISGNLWDKDQRAPYYNYKDPAGHFHQVWYDNPQSISLKATYIQNYRLRGIGMWNANCLD
  YSGDAVAKQQTEEMWEVLKPKLLQR
• Function: Involved in the degradation of asparagine-linked glycoproteins. Hydrolyze of N-acetyl-beta-D-glucosamine (1-4)N-acetylglucosamine chitobiose core from the reducing end of the bond, it requires prior cleavage by glycosylasparaginase.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[1]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Liver cancer	DISDE4BI	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[8]
Urinary tract infection	DISMT6UV	Strong	Biomarker	[9]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[10]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[11]
Aplasia cutis congenita	DISMDAYM	Limited	Genetic Variation	[12]
Corpus callosum, agenesis of	DISO9P40	Limited	Genetic Variation	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Di-N-acetylchitobiase (CTBS).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Di-N-acetylchitobiase (CTBS).	[21]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Di-N-acetylchitobiase (CTBS).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Di-N-acetylchitobiase (CTBS).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Di-N-acetylchitobiase (CTBS).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Di-N-acetylchitobiase (CTBS).	[17]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Di-N-acetylchitobiase (CTBS).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Di-N-acetylchitobiase (CTBS).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Di-N-acetylchitobiase (CTBS).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Di-N-acetylchitobiase (CTBS).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Di-N-acetylchitobiase (CTBS).	[23]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Di-N-acetylchitobiase (CTBS).	[24]

References

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• [10] Hypoglossal Motor Neuron Death Via Intralingual CTB-saporin (CTB-SAP) Injections Mimic Aspects of Amyotrophic Lateral Sclerosis (ALS) Related to Dysphagia.Neuroscience. 2018 Oct 15;390:303-316. doi: 10.1016/j.neuroscience.2018.08.026. Epub 2018 Sep 1.
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• [17] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [18] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
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