Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8IOD03)

• DOT Name: Acireductone dioxygenase (ADI1)
• Synonyms: Acireductone dioxygenase (Fe(2+)-requiring); ARD'; Fe-ARD; EC 1.13.11.54; Acireductone dioxygenase (Ni(2+)-requiring); ARD; Ni-ARD; EC 1.13.11.53; Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein 1; MTCBP-1; Submergence-induced protein-like factor; Sip-L
• Gene Name: ADI1
• Related Disease:
  Arthritis
  Chronic kidney disease
  Spondylocarpotarsal synostosis syndrome
  Alzheimer disease
  Cardiac failure
  Congestive heart failure
  Familial Alzheimer disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  HIV infectious disease
  Leber hereditary optic neuropathy
  Neoplasm
  Pancreatic tumour
  Polyp
  Prostate carcinoma
  Prostate neoplasm
  Rheumatoid arthritis
  Adult glioblastoma
  Brain neoplasm
  Glioblastoma multiforme
  Peripheral arterial disease
  Varicose veins
  Dementia
  Parkinson disease
  Prostate cancer
• UniProt ID: MTND_HUMAN
• PDB ID: 4QGN; 7JXG
• EC Number: 1.13.11.53; 1.13.11.54
• Pfam ID: PF03079
• Sequence:
  MVQAWYMDDAPGDPRQPHRPDPGRPVGLEQLRRLGVLYWKLDADKYENDPELEKIRRERN
  YSWMDIITICKDKLPNYEEKIKMFYEEHLHLDDEIRYILDGSGYFDVRDKEDQWIRIFME
  KGDMVTLPAGIYHRFTVDEKNYTKAMRLFVGEPVWTAYNRPADHFEARGQYVKFLAQTA
• Function: Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site. Fe-containing acireductone dioxygenase (Fe-ARD) produces formate and 2-keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of methionine in the methionine recycle pathway. Ni-containing acireductone dioxygenase (Ni-ARD) produces methylthiopropionate, carbon monoxide and formate, and does not lie on the methionine recycle pathway. Also down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line.
• Tissue Specificity: Detected in heart, colon, lung, stomach, brain, spleen, liver, skeletal muscle and kidney.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Methionine salvage pathway (R-HSA-1237112)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Chronic kidney disease	DISW82R7	Definitive	Biomarker	[2]
Spondylocarpotarsal synostosis syndrome	DISF9VP3	Definitive	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Genetic Variation	[4]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[4]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[8]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[10]
Polyp	DISRSLYF	Strong	Genetic Variation	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[13]
Brain neoplasm	DISY3EKS	moderate	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[13]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[14]
Varicose veins	DISIMBN2	moderate	Biomarker	[14]
Dementia	DISXL1WY	Limited	Genetic Variation	[15]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[15]
Prostate cancer	DISF190Y	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Acireductone dioxygenase (ADI1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acireductone dioxygenase (ADI1).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Acireductone dioxygenase (ADI1).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acireductone dioxygenase (ADI1).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Acireductone dioxygenase (ADI1).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acireductone dioxygenase (ADI1).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Acireductone dioxygenase (ADI1).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Acireductone dioxygenase (ADI1).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Acireductone dioxygenase (ADI1).	[24]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Acireductone dioxygenase (ADI1).	[20]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Acireductone dioxygenase (ADI1).	[25]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Acireductone dioxygenase (ADI1).	[26]
Dutasteride	DMQ4TJK	Approved	Dutasteride decreases the expression of Acireductone dioxygenase (ADI1).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Acireductone dioxygenase (ADI1).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Acireductone dioxygenase (ADI1).	[28]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Acireductone dioxygenase (ADI1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acireductone dioxygenase (ADI1).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Acireductone dioxygenase (ADI1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Acireductone dioxygenase (ADI1).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Acireductone dioxygenase (ADI1).	[32]
[3H]mibolerone	DM6HDKQ	Investigative	[3H]mibolerone increases the expression of Acireductone dioxygenase (ADI1).	[12]

References

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