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Gene and Protein Information  |
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| 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 |
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| Alphafold | P05164 (Hs), P11247 (Mm) |
| CATH/Gene3D | 1.10.640.10 |
| ChEMBL Target | CHEMBL2439 (Hs), CHEMBL2440 (Mm) |
| Ensembl Gene | ENSG00000005381 (Hs), ENSMUSG00000009350 (Mm), ENSRNOG00000008310 (Rn) |
| Entrez Gene | 4353 (Hs), 17523 (Mm), 303413 (Rn) |
| Human Protein Atlas | ENSG00000005381 (Hs) |
| KEGG Gene | hsa:4353 (Hs), mmu:17523 (Mm), rno:303413 (Rn) |
| OMIM | 606989 (Hs) |
| Pharos | P05164 (Hs) |
| RefSeq Nucleotide | NM_000250 (Hs), NM_010824 (Mm), NM_001107036 (Rn) |
| RefSeq Protein | NP_000241 (Hs), NP_034954 (Mm), NP_001100506 (Rn) |
| UniProtKB | P05164 (Hs), P11247 (Mm) |
| Wikipedia | MPO (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||
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| Physiological Consequences of Altering Gene Expression
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| Clinically-Relevant Mutations and Pathophysiology
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| 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. |
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. ncats.nih.gov, https://ncats.nih.gov/files/AZD3241-2016.pdf
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]
1.-.-.- Oxidoreductases: myeloperoxidase. Last modified on 26/08/2022. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2789.
target has curated data in GtoImmuPdb
