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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2789

Nomenclature: myeloperoxidase

Family: 1.-.-.- Oxidoreductases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 745 17q22 MPO myeloperoxidase
Mouse - 718 11 C Mpo myeloperoxidase
Rat - 458 10q26 Mpo myeloperoxidase
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF-06282999 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.5 pKi 11
pKi 6.5 (Ki 3.16x10-7 M) [11]
Description: Inhibition of the peroxidase activity of MPO isolated from human polynuclear leukocytes.
mitiperstat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 4
pIC50 9.1 (IC50 7x10-10 M) [4]
mitiperstat Small molecule or natural product Click here for species-specific activity table Hs Irreversible inhibition 8.8 pIC50 5
pIC50 8.8 (IC50 1.5x10-9 M) [5]
compound 28 [PMID: 28671460] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.4 pIC50 12
pIC50 7.4 (IC50 4.4x10-8 M) [12]
aminopyridine 2 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 8
pIC50 6.8 (IC50 1.6x10-7 M) [8]
Description: In a fluorescent MPO peroxidation biochemical assay.
AZD5904 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.7 pIC50 13
pIC50 6.7 (IC50 2x10-7 M) [13]
Description: Inhibition of the chlorination activity of MPO
verdiperstat Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.2 pIC50 2
pIC50 6.2 (IC50 6.3x10-7 M) [2]
Description: In a biochemical in vitro assay.
Inhibitor Comments
The ex vivo IC50 for inhibition of MPO activity by aminopyridine 2 is 1900 nM in human plasma [8].
Immunopharmacology Comments
Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme whose peroxidase enzymatic activity generates hypohalous acids that constitute the major component responsible for neutrophil antimicrobial activity, and as such MPO participates in the innate immune defense mechanism. Since the discovery that MPO-derived oxidants contribute towards the propagation of inflammatory diseases (including cystic fibrosis, chronic obstructive pulmonary disease, Parkinson's disease, rheumatoid arthritis, acute kidney injury, atherosclerosis and cardiovascular disease) [6,10], the pharma industry has been on the hunt for drug-like inhibitors of pathological MPO activity [7].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Physiological Consequences of Altering Gene Expression Click here for help
Over-expression of MPO in hematopoietic cells exacerbates atherogenesis in mice.
Species:  Mouse
Tissue:  Hematopoietic cells.
Technique:  Transgenic over-expression.
References:  3,9
MPO deficient mice are protected in a model of myocardial infarction.
Species:  Mouse
References:  1
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
Disease:  Myeloperoxidase deficiency; MPOD
OMIM: 254600
Orphanet: ORPHA2587
General Comments
Myeloperoxidase (MPO) is a heme enzyme that participates in the formation of microbicidal reactive oxidants. It is most abundantly expressed in neutrophil granulocytes. MPO released from neutrophils and monocytes catalyzes the formation of reactive chlorinating species that are capable of oxidizing proteins and altering biological function.


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1. Askari AT, Brennan ML, Zhou X, Drinko J, Morehead A, Thomas JD, Topol EJ, Hazen SL, Penn MS. (2003) Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction. J Exp Med, 197 (5): 615-24. [PMID:12615902]

2. AstraZeneca. AZD3241. Accessed on 20/08/2018. Modified on 20/08/2018.,

3. Castellani LW, Chang JJ, Wang X, Lusis AJ, Reynolds WF. (2006) Transgenic mice express human MPO -463G/A alleles at atherosclerotic lesions, developing hyperlipidemia and obesity in -463G males. J Lipid Res, 47 (7): 1366-77. [PMID:16639078]

4. Gan LM, Lagerström-Fermér M, Ericsson H, Nelander K, Lindstedt EL, Michaëlsson E, Kjaer M, Heijer M, Whatling C, Fuhr R. (2019) Safety, tolerability, pharmacokinetics and effect on serum uric acid of the myeloperoxidase inhibitor AZD4831 in a randomized, placebo-controlled, phase I study in healthy volunteers. Br J Clin Pharmacol, 85 (4): 762-770. [PMID:30618054]

5. Inghardt T, Antonsson T, Ericsson C, Hovdal D, Johannesson P, Johansson C, Jurva U, Kajanus J, Kull B, Michaëlsson E et al.. (2022) Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction. J Med Chem, 65 (17): 11485-11496. [PMID:36005476]

6. Klebanoff SJ. (2005) Myeloperoxidase: friend and foe. J Leukoc Biol, 77 (5): 598-625. [PMID:15689384]

7. Malle E, Furtmüller PG, Sattler W, Obinger C. (2007) Myeloperoxidase: a target for new drug development?. Br J Pharmacol, 152 (6): 838-54. [PMID:17592500]

8. Marro ML, Patterson AW, Lee L, Deng L, Reynolds A, Ren X, Axford L, Patnaik A, Hollis-Symynkywicz M, Casson N et al.. (2018) Discovery of 1-((6-Aminopyridin-3-yl)Methyl)-3-(4-Bromophenyl)Urea as a Potent, Irreversible Myeloperoxidase Inhibitor. J Pharmacol Exp Ther, 367 (1): 147-154. [PMID:30076263]

9. McMillen TS, Heinecke JW, LeBoeuf RC. (2005) Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation, 111 (21): 2798-804. [PMID:15911707]

10. Nussbaum C, Klinke A, Adam M, Baldus S, Sperandio M. (2013) Myeloperoxidase: a leukocyte-derived protagonist of inflammation and cardiovascular disease. Antioxid Redox Signal, 18 (6): 692-713. [PMID:22823200]

11. Ruggeri RB, Buckbinder L, Bagley SW, Carpino PA, Conn EL, Dowling MS, Fernando DP, Jiao W, Kung DW, Orr ST et al.. (2015) Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases. J Med Chem, 58 (21): 8513-28. [PMID:26509551]

12. Soubhye J, Chikh Alard I, Aldib I, Prévost M, Gelbcke M, De Carvalho A, Furtmüller PG, Obinger C, Flemmig J, Tadrent S et al.. (2017) Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure. J Med Chem, 60 (15): 6563-6586. [PMID:28671460]

13. Tidén AK, Sjögren T, Svensson M, Bernlind A, Senthilmohan R, Auchère F, Norman H, Markgren PO, Gustavsson S, Schmidt S et al.. (2011) 2-thioxanthines are mechanism-based inactivators of myeloperoxidase that block oxidative stress during inflammation. J Biol Chem, 286 (43): 37578-89. [PMID:21880720]

How to cite this page

1.-.-.- Oxidoreductases: myeloperoxidase. Last modified on 26/08/2022. Accessed on 21/07/2024. IUPHAR/BPS Guide to PHARMACOLOGY,