Details of Drug Off-Target (DOT)

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

• DOT Name: Myeloperoxidase (MPO)
• Synonyms: MPO; EC 1.11.2.2
• Gene Name: MPO
• UniProt ID: PERM_HUMAN
• PDB ID: 1CXP; 1D2V; 1D5L; 1D7W; 1DNU; 1DNW; 1MHL; 1MYP; 3F9P; 3ZS0; 3ZS1; 4C1M; 4DL1; 4EJX; 5FIW; 5MFA; 5UZU; 6AZP; 6BMT; 7OIH
• EC Number: 1.11.2.2
• Pfam ID: PF03098
• Sequence:
  MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTS
  LVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLH
  VALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMC
  NNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTD
  QLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPND
  PRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQL
  GLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLL
  REHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYR
  SYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLE
  GGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYN
  AWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPL
  LACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMS
  NSYPRDFVNCSTLPALNLASWREAS
• Function: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. Mediates the proteolytic cleavage of alpha-1-microglobulin to form t-alpha-1-microglobulin, which potently inhibits oxidation of low-density lipoprotein particles and limits vascular damage.
• KEGG Pathway:
  Drug metabolism - other enzymes (hsa00983)
  Phagosome (hsa04145)
  Neutrophil extracellular trap formation (hsa04613)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
• Reactome Pathway:
  Events associated with phagocytolytic activity of PMN cells (R-HSA-8941413)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:HS00140-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 11 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Myeloperoxidase (MPO) increases the Respiratory, thoracic and mediastinal disorders ADR of Acetaminophen.	[30]
Arsenic	DMTL2Y1	Approved	Myeloperoxidase (MPO) increases the response to substance of Arsenic.	[31]
Ethanol	DMDRQZU	Approved	Myeloperoxidase (MPO) increases the Pancreatitis acute ADR of Ethanol.	[30]
Aspirin	DM672AH	Approved	Myeloperoxidase (MPO) increases the Haemorrhagic disorder ADR of Aspirin.	[30]
Ibuprofen	DM8VCBE	Approved	Myeloperoxidase (MPO) increases the Ventricular fibrillation ADR of Ibuprofen.	[30]
Sulfasalazine	DMICA9H	Approved	Myeloperoxidase (MPO) increases the Vasculitis ADR of Sulfasalazine.	[30]
Amodiaquine	DME4RA8	Approved	Myeloperoxidase (MPO) increases the Hepatotoxicity ADR of Amodiaquine.	[30]
Allopurinol	DMLPAOB	Approved	Myeloperoxidase (MPO) increases the Reperfusion injury ADR of Allopurinol.	[30]
Clonidine	DM6RZ9Q	Approved	Myeloperoxidase (MPO) increases the Agranulocytosis ADR of Clonidine.	[30]
Dapsone	DM4LT8A	Approved	Myeloperoxidase (MPO) increases the Agranulocytosis ADR of Dapsone.	[30]
Sulfamethoxazole	DMB08GE	Approved	Myeloperoxidase (MPO) increases the Agranulocytosis ADR of Sulfamethoxazole.	[30]

This DOT Affected the Biotransformations of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Myeloperoxidase (MPO) increases the chemical synthesis of Hydroquinone.	[32]
Nitric Oxide	DM1RBYG	Approved	Myeloperoxidase (MPO) increases the oxidation of Nitric Oxide.	[34]
Isoniazid	DM5JVS3	Approved	Myeloperoxidase (MPO) increases the oxidation of Isoniazid.	[35]
Phenol	DM1QSM3	Phase 2/3	Myeloperoxidase (MPO) increases the hydroxylation of Phenol.	[32]
7-hydroxycoumarin	DMTMNO7	Investigative	Myeloperoxidase (MPO) increases the oxidation of 7-hydroxycoumarin.	[23]
Phenolsulfonphthalein	DMCTUAD	Investigative	Myeloperoxidase (MPO) increases the oxidation of Phenolsulfonphthalein.	[37]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Myeloperoxidase (MPO) increases the metabolism of Etoposide.	[33]
Thiabendazole	DM7YCK3	Approved	Myeloperoxidase (MPO) increases the metabolism of Thiabendazole.	[36]

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 Myeloperoxidase (MPO).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myeloperoxidase (MPO).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myeloperoxidase (MPO).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the activity of Myeloperoxidase (MPO).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone affects the expression of Myeloperoxidase (MPO).	[5]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Myeloperoxidase (MPO).	[6]
Clozapine	DMFC71L	Approved	Clozapine increases the activity of Myeloperoxidase (MPO).	[7]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Myeloperoxidase (MPO).	[8]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Myeloperoxidase (MPO).	[9]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the activity of Myeloperoxidase (MPO).	[11]
Abacavir	DMMN36E	Approved	Abacavir increases the expression of Myeloperoxidase (MPO).	[12]
Salicyclic acid	DM2F8XZ	Approved	Salicyclic acid increases the activity of Myeloperoxidase (MPO).	[11]
Aluminium	DM6ECN9	Approved	Aluminium increases the expression of Myeloperoxidase (MPO).	[13]
Propylthiouracil	DM6D7N8	Approved	Propylthiouracil decreases the activity of Myeloperoxidase (MPO).	[14]
Bivalirudin	DMECRX1	Approved	Bivalirudin decreases the expression of Myeloperoxidase (MPO).	[15]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of Myeloperoxidase (MPO).	[11]
Hirudin	DMYOC29	Phase 4	Hirudin decreases the activity of Myeloperoxidase (MPO).	[16]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the activity of Myeloperoxidase (MPO).	[17]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Myeloperoxidase (MPO).	[18]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the activity of Myeloperoxidase (MPO).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Myeloperoxidase (MPO).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myeloperoxidase (MPO).	[21]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Myeloperoxidase (MPO).	[22]
PMID28454500-Compound-95	DM9L2VR	Patented	PMID28454500-Compound-95 decreases the activity of Myeloperoxidase (MPO).	[23]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the activity of Myeloperoxidase (MPO).	[11]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Myeloperoxidase (MPO).	[24]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the activity of Myeloperoxidase (MPO).	[25]
Fmet-leu-phe	DMQ391A	Investigative	Fmet-leu-phe increases the activity of Myeloperoxidase (MPO).	[28]
Syringic Acid	DM802V7	Investigative	Syringic Acid decreases the activity of Myeloperoxidase (MPO).	[11]
Dimethylformamide	DML6O4N	Investigative	Dimethylformamide increases the expression of Myeloperoxidase (MPO).	[29]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Penicillamine	DM40EF6	Approved	Penicillamine decreases the secretion of Myeloperoxidase (MPO).	[10]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the secretion of Myeloperoxidase (MPO).	[26]
Beta-D-Glucose	DM5IHYP	Investigative	Beta-D-Glucose increases the secretion of Myeloperoxidase (MPO).	[27]

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