Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEA3U9Y)

• DME Name: Myeloperoxidase (MPO)
• Synonyms: Myeloperoxidase heavy chain; Myeloperoxidase light chain; 84 kDa myeloperoxidase; 89 kDa myeloperoxidase; MPO
• Gene Name: MPO
• UniProt ID: PERM_HUMAN
• INTEDE ID: DME0096
• Gene ID: 4353
• EC Number:
  EC: 1.11.2.2
  Oxidoreductase
  Peroxidase
  Peroxygenase
  EC: 1.11.2.2
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTS
  LVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLH
  VALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMC
  NNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTD
  QLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPND
  PRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQL
  GLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLL
  REHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYR
  SYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLE
  GGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYN
  AWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPL
  LACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMS
  NSYPRDFVNCSTLPALNLASWREAS
• Function: This enzyme oxidizes tyrosine to tyrosyl radical using hydrogen peroxide as an oxidizing agent.
• KEGG Pathway:
  Acute myeloid leukemia (hsa05221)
  Drug metabolism - other enzymes (hsa00983)
  Phagosome (hsa04145)
  Transcriptional misregulation in cancer (hsa05202)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Events associated with phagocytolytic activity of PMN cells (R-HSA-8941413)

Molecular Interaction Atlas (MIA) of This DME

7 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[8]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[9]
Cysteamine	DMSYFM8	Nephropathic cystinosis	5C60	Approved	[10]
Dapsone	DM4LT8A	Acne vulgaris	ED80	Approved	[11]
Glutethimide	DMGE0CW	Insomnia	7A00-7A0Z	Approved	[12]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[8]
Ticlopidine	DMO946V	Acute coronary syndrome	BA41	Approved	[11]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	5.73E-13	-7.73E-01	-6.87E-01
Alopecia	ED70	Skin from scalp	5.78E-01	-4.11E-04	-2.83E-03
Alzheimer's disease	8A20	Entorhinal cortex	2.64E-01	-7.34E-02	-4.45E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	7.13E-01	1.67E-01	8.93E-01
Aortic stenosis	BB70	Calcified aortic valve	9.02E-01	4.17E-02	9.15E-02
Apnea	7A40	Hyperplastic tonsil	9.12E-01	1.87E-02	2.48E-01
Arthropathy	FA00-FA5Z	Peripheral blood	2.08E-02	3.33E-01	1.03E+00
Asthma	CA23	Nasal and bronchial airway	9.25E-01	-8.04E-03	-3.19E-02
Atopic dermatitis	EA80	Skin	7.76E-02	4.73E-02	5.36E-01
Autism	6A02	Whole blood	5.21E-01	1.54E-02	6.28E-02
Autoimmune uveitis	9A96	Peripheral monocyte	9.41E-01	-2.60E-01	-5.71E-01
Autosomal dominant monocytopenia	4B04	Whole blood	1.85E-01	2.42E-01	6.95E-01
Bacterial infection of gingival	1C1H	Gingival tissue	3.82E-01	1.83E-02	1.46E-01
Batten disease	5C56.1	Whole blood	4.43E-01	6.12E-02	2.55E-01
Behcet's disease	4A62	Peripheral blood	5.55E-01	-1.66E-01	-3.26E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	5.18E-01	-2.77E-02	-2.18E-01
Bladder cancer	2C94	Bladder tissue	6.79E-05	3.78E-01	3.01E+00
Breast cancer	2C60-2C6Z	Breast tissue	1.15E-14	-1.04E-01	-6.05E-01
Cardioembolic stroke	8B11.20	Whole blood	1.66E-02	2.70E-01	4.15E-01
Cervical cancer	2C77	Cervical tissue	8.13E-01	2.84E-02	1.35E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	2.25E-01	2.94E-02	9.40E-02
Chronic hepatitis C	1E51.1	Whole blood	4.63E-01	1.62E-03	7.09E-03
Chronic obstructive pulmonary disease	CA22	Lung tissue	3.51E-03	1.01E-01	7.46E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	2.78E-01	9.40E-03	5.97E-02
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	4.00E-01	4.47E-02	3.27E-01
Colon cancer	2B90	Colon tissue	1.15E-01	2.71E-02	1.58E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	7.63E-02	6.51E-02	2.81E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	3.16E-01	1.85E-02	1.81E-01
Endometriosis	GA10	Endometrium tissue	5.32E-01	7.66E-03	4.81E-02
Familial hypercholesterolemia	5C80.00	Peripheral blood	4.30E-01	-6.66E-02	-7.78E-02
Familial hypercholesterolemia	5C80.00	Whole blood	9.81E-02	1.30E-01	4.75E-01
Gastric cancer	2B72	Gastric tissue	9.16E-01	-2.45E-02	-3.75E-01
Glioblastopma	2A00.00	Nervous tissue	2.17E-30	-2.01E-01	-6.34E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	3.65E-01	-2.90E-01	-1.07E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	6.85E-06	-4.93E-01	-3.21E+00
Head and neck cancer	2D42	Head and neck tissue	4.27E-01	-1.26E-03	-8.79E-03
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	5.32E-01	-5.01E-02	-2.56E-01
Huntington's disease	8A01.10	Whole blood	5.54E-01	6.03E-02	4.33E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.23E-01	-1.72E-01	-3.32E-01
Immunodeficiency	4A00-4A20	Peripheral blood	2.26E-01	5.16E-02	6.64E-01
Influenza	1E30	Whole blood	4.51E-02	6.17E-01	2.72E+00
Interstitial cystitis	GC00.3	Bladder tissue	4.99E-01	2.29E-02	3.23E-01
Intracranial aneurysm	8B01.0	Intracranial artery	8.17E-03	2.52E-01	1.88E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	7.20E-01	5.17E-02	2.39E-01
Ischemic stroke	8B11	Peripheral blood	2.11E-01	1.17E-01	2.60E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.31E-06	2.99E-01	5.73E-01
Lateral sclerosis	8B60.4	Skin	6.24E-02	1.04E-01	1.35E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	4.11E-01	4.58E-03	1.92E-02
Liver cancer	2C12.0	Liver tissue	4.22E-06	-1.76E-01	-1.05E+00
Liver failure	DB99.7-DB99.8	Liver tissue	6.22E-02	2.08E-01	9.19E-01
Lung cancer	2C25	Lung tissue	1.05E-11	-1.21E-01	-5.76E-01
Lupus erythematosus	4A40	Whole blood	4.89E-09	3.48E-01	6.81E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.62E-01	2.70E-02	2.24E-01
Major depressive disorder	6A70-6A7Z	Whole blood	3.00E-02	1.31E-01	2.99E-01
Melanoma	2C30	Skin	7.30E-01	-7.29E-03	-2.09E-02
Multiple myeloma	2A83.1	Peripheral blood	1.35E-01	-7.27E-02	-4.09E-01
Multiple myeloma	2A83.1	Bone marrow	1.71E-01	-4.10E-01	-6.76E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.23E-01	1.09E-01	7.35E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.00E-14	-4.20E-01	-1.22E+00
Myelofibrosis	2A20.2	Whole blood	1.11E-02	9.78E-01	4.31E+00
Myocardial infarction	BA41-BA50	Peripheral blood	1.18E-02	2.99E-01	5.82E-01
Myopathy	8C70.6	Muscle tissue	2.66E-01	-3.78E-02	-3.07E-01
Neonatal sepsis	KA60	Whole blood	3.39E-22	1.15E+00	3.46E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.85E-05	-3.71E-01	-2.54E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	9.34E-01	-9.57E-04	-7.06E-03
Obesity related type 2 diabetes	5A11	Omental adipose tissue	9.94E-01	-3.61E-02	-3.43E-01
Olive pollen allergy	CA08.00	Peripheral blood	3.81E-02	2.66E-01	1.22E+00
Oral cancer	2B6E	Oral tissue	3.76E-05	-1.91E-01	-1.00E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	8.46E-01	-6.45E-02	-3.87E-01
Osteoporosis	FB83.1	Bone marrow	9.54E-01	1.05E-01	8.00E-01
Ovarian cancer	2C73	Ovarian tissue	6.23E-01	1.20E-02	4.70E-02
Pancreatic cancer	2C10	Pancreas	5.41E-02	-7.74E-02	-2.87E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	2.88E-01	-2.34E-02	-1.58E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	2.58E-04	1.22E+00	1.64E+00
Pituitary cancer	2D12	Pituitary tissue	6.47E-02	-3.26E-01	-5.24E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	6.72E-02	-3.94E-01	-5.34E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.77E-01	-1.95E-03	-1.35E-02
Polycythemia vera	2A20.4	Whole blood	1.79E-02	1.33E-01	6.29E-01
Pompe disease	5C51.3	Biceps muscle	1.40E-02	-9.52E-02	-8.50E-01
Preterm birth	KA21.4Z	Myometrium	1.67E-01	-8.35E-02	-8.25E-01
Prostate cancer	2C82	Prostate	2.94E-02	-1.48E-01	-4.83E-01
Psoriasis	EA90	Skin	3.65E-02	-2.58E-02	-1.12E-01
Rectal cancer	2B92	Rectal colon tissue	4.94E-01	-3.55E-02	-2.47E-01
Renal cancer	2C90-2C91	Kidney	4.56E-03	-3.62E-01	-1.04E+00
Retinoblastoma	2D02.2	Uvea	1.03E-03	-1.60E-01	-1.36E+00
Rheumatoid arthritis	FA20	Synovial tissue	9.11E-02	-3.24E-01	-9.26E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	8.97E-01	-2.44E-03	-2.03E-02
Schizophrenia	6A20	Prefrontal cortex	5.26E-02	7.52E-02	1.33E-01
Schizophrenia	6A20	Superior temporal cortex	6.26E-01	-2.67E-02	-3.53E-01
Scleroderma	4A42.Z	Whole blood	2.41E-02	3.46E-01	8.45E-01
Seizure	8A60-8A6Z	Whole blood	2.17E-01	-8.25E-02	-2.41E-01
Sensitive skin	EK0Z	Skin	7.23E-01	-3.40E-02	-2.94E-01
Sepsis with septic shock	1G41	Whole blood	1.05E-90	9.61E-01	3.28E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	9.03E-01	-2.29E-01	-6.84E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	7.33E-01	4.11E-02	2.37E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	8.56E-01	1.33E-01	5.11E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.56E-01	1.54E-01	1.04E+00
Skin cancer	2C30-2C3Z	Skin	9.46E-03	-9.09E-02	-3.38E-01
Thrombocythemia	3B63	Whole blood	3.02E-02	7.51E-02	3.08E-01
Thrombocytopenia	3B64	Whole blood	1.00E-01	1.86E+00	1.35E+00
Thyroid cancer	2D10	Thyroid	3.39E-01	2.02E-02	6.17E-02
Tibial muscular dystrophy	8C75	Muscle tissue	1.50E-01	-1.63E-01	-9.30E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	9.91E-02	3.49E-01	2.18E+00
Type 2 diabetes	5A11	Liver tissue	7.99E-01	-4.18E-02	-3.31E-01
Ureter cancer	2C92	Urothelium	1.57E-01	-1.07E-01	-6.93E-01
Uterine cancer	2C78	Endometrium tissue	8.98E-01	4.98E-02	2.29E-01
Vitiligo	ED63.0	Skin	5.21E-01	1.44E-02	2.44E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Myeloperoxidase (MPO) DTT Info
• DME DTT Type: Clinical trial

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E-101	DMM1YC4	Infectious disease	1A00-CA43.1	Phase 3	[1]
Mitiperstat	DM0BL2G	Heart failure with preserved ejection fraction	BD11.0	Phase 2/3	[2]
AZD-3241	DMANC59	Parkinson disease	8A00.0	Phase 2	[3]
AZD4831	DMRP3N8	Heart failure	BD10-BD13	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD5904	DM8SCON	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[5]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-aminobenzoic acid hydrazide	DMP2GN7	Discovery agent	N.A.	Investigative	[6]
INV-311	DM8BZVI	Inflammation	1A00-CA43.1	Investigative	[7]

References

• [1] In vitro antibacterial activity of E-101 Solution, a novel myeloperoxidase-mediated antimicrobial, against Gram-positive and Gram-negative pathogens. J Antimicrob Chemother. 2011 Feb;66(2):335-42.
• [2] Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction. J Med Chem. 2022 Sep 8;65(17):11485-11496.
• [3] Effect of the myeloperoxidase inhibitor AZD3241 on microglia: a PET study in Parkinson's disease. Brain. 2015 Sep;138(Pt 9):2687-700.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [6] Myeloperoxidase expression as a potential determinant of parthenolide-induced apoptosis in leukemia bulk and leukemia stem cells. J Pharmacol Exp Ther. 2010 Nov;335(2):389-400.
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2789).
• [8] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [9] Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production. Res Vet Sci. 2010 Apr;88(2):218-26.
• [10] Thiols as peroxidase substrates. Free Radic Biol Med. 1993 Feb;14(2):167-75.
• [11] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [12] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.