Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVCZPI)

• DTT Name: Myeloperoxidase (MPO)
• Synonyms: MPO
• Gene Name: MPO
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peroxidases
• UniProt ID: PERM_HUMAN
• TTD ID: T23471
• EC Number: EC 1.11.2.2
• 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 acidin physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
• KEGG Pathway:
  Phagosome (hsa04145)
  Transcriptional misregulation in cancer (hsa05202)
• Reactome Pathway:
  Events associated with phagocytolytic activity of PMN cells (R-HSA-8941413)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:HS00140-MON

Molecular Interaction Atlas (MIA) of This DTT

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]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	2.88E-01	-0.02	-0.16

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Myeloperoxidase (MPO) DME Info
• Gene Name: MPO

7 Approved Drug(s) Metabolized by This DTT

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]

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.