Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRLGQ7V)

• DOT Name: 2-aminoethanethiol dioxygenase (ADO)
• Synonyms: EC 1.13.11.19; Cysteamine dioxygenase
• Gene Name: ADO
• Related Disease:
  Acute myocardial infarction
  Advanced cancer
  Autosomal dominant osteopetrosis
  Behcet disease
  Bone disease
  Cardiac failure
  Cardiovascular disease
  Carney complex
  Cervical cancer
  Cervical carcinoma
  Chronic obstructive pulmonary disease
  Colitis
  Congestive heart failure
  Estrogen-receptor positive breast cancer
  Infantile malignant osteopetrosis
  Osteopetrosis
  Pulmonary arterial hypertension
  Uveitis
  Ventricular septal defect
  Neoplasm
  Atrial septal defect
• UniProt ID: AEDO_HUMAN
• PDB ID: 7REI
• EC Number: 1.13.11.19
• Pfam ID: PF07847
• Sequence:
  MPRDNMASLIQRIARQACLTFRGSGGGRGASDRDAASGPEAPMQPGFPENLSKLKSLLTQ
  LRAEDLNIAPRKATLQPLPPNLPPVTYMHIYETDGFSLGVFLLKSGTSIPLHDHPGMHGM
  LKVLYGTVRISCMDKLDAGGGQRPRALPPEQQFEPPLQPREREAVRPGVLRSRAEYTEAS
  GPCILTPHRDNLHQIDAVEGPAAFLDILAPPYDPDDGRDCHYYRVLEPVRPKEASSSACD
  LPREVWLLETPQADDFWCEGEPYPGPKVFP
• Function: Plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate. Catalyzes the oxidation of cysteamine (2-aminoethanethiol) to hypotaurine. Catalyzes the oxidation of regulators of G-protein signaling 4 (RGS4) and 5 (RGS5) and interleukin-32 (IL32).
• KEGG Pathway:
  Taurine and hypotaurine metabolism (hsa00430)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Degradation of cysteine and homocysteine (R-HSA-1614558)
• BioCyc Pathway: MetaCyc:HS17749-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autosomal dominant osteopetrosis	DISS69AL	Strong	Genetic Variation	[3]
Behcet disease	DISSYMBS	Strong	Biomarker	[4]
Bone disease	DISE1F82	Strong	Genetic Variation	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[7]
Carney complex	DISVL3IP	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[9]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[9]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[10]
Colitis	DISAF7DD	Strong	Biomarker	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Genetic Variation	[12]
Infantile malignant osteopetrosis	DIS8C3LZ	Strong	Biomarker	[3]
Osteopetrosis	DIS7GHNM	Strong	Genetic Variation	[13]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Genetic Variation	[14]
Uveitis	DISV0RYS	Strong	Genetic Variation	[15]
Ventricular septal defect	DISICO41	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Disputed	Biomarker	[17]
Atrial septal defect	DISJT76B	Limited	Biomarker	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of 2-aminoethanethiol dioxygenase (ADO).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 2-aminoethanethiol dioxygenase (ADO).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 2-aminoethanethiol dioxygenase (ADO).	[21]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2-aminoethanethiol dioxygenase (ADO).	[22]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of 2-aminoethanethiol dioxygenase (ADO).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-aminoethanethiol dioxygenase (ADO).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 2-aminoethanethiol dioxygenase (ADO).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 2-aminoethanethiol dioxygenase (ADO).	[27]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of 2-aminoethanethiol dioxygenase (ADO).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of 2-aminoethanethiol dioxygenase (ADO).	[24]

References

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• [9] Cervical cancer cells produce TGF-1 through the CD73-adenosine pathway and maintain CD73 expression through the autocrine activity of TGF-1.Cytokine. 2019 Jun;118:71-79. doi: 10.1016/j.cyto.2018.09.018. Epub 2018 Oct 6.
• [10] External Validation Of The Updated ADO Score In COPD Patients From The Birmingham COPD Cohort.Int J Chron Obstruct Pulmon Dis. 2019 Oct 24;14:2395-2407. doi: 10.2147/COPD.S212381. eCollection 2019.
• [11] Contribution of adenosine A2B receptors to inflammatory parameters of experimental colitis.J Immunol. 2009 Apr 15;182(8):4957-64. doi: 10.4049/jimmunol.0801324.
• [12] Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.Am J Hum Genet. 2015 Jul 2;97(1):22-34. doi: 10.1016/j.ajhg.2015.05.002. Epub 2015 Jun 11.
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• [14] Interventional re-opening of a PDA for reverse potts shunt circulation after ADO i implantation in a child.Catheter Cardiovasc Interv. 2017 Mar 1;89(4):E133-E136. doi: 10.1002/ccd.26680. Epub 2016 Aug 12.
• [15] Uveitis genetics.Exp Eye Res. 2020 Jan;190:107853. doi: 10.1016/j.exer.2019.107853. Epub 2019 Oct 25.
• [16] Treatment of congenital non-ductal shunt lesions with the amplatzer duct occluder II.Catheter Cardiovasc Interv. 2017 May;89(6):E185-E193. doi: 10.1002/ccd.25250. Epub 2013 Nov 18.
• [17] Tumor immune evasion arises through loss of TNF sensitivity.Sci Immunol. 2018 May 18;3(23):eaar3451. doi: 10.1126/sciimmunol.aar3451.
• [18] Off-label use of Amplatzer Duct Occluder II additional sizes.J Cardiovasc Med (Hagerstown). 2017 Jun;18(6):436-442. doi: 10.2459/JCM.0000000000000491.
• [19] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
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• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [22] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [23] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [24] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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• [26] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
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• [28] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.