MPO
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Summary
MPO (myeloperoxidase, HGNC:7218) is a protein-coding gene on chromosome 17q22, encoding Myeloperoxidase (P05164). Peroxidase that plays a central role in the host defense system of polymorphonuclear leukocytes by mediating both (1) formation of neutrophil extracellular trap (NETs) and (2) microbicidal activity.
Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Produced as a single chain precursor, myeloperoxidase is subsequently cleaved into a light and heavy chain. The mature myeloperoxidase is a tetramer composed of 2 light chains and 2 heavy chains. This enzyme produces hypohalous acids central to the microbicidal activity of neutrophils.
Source: NCBI Gene 4353 — RefSeq curated summary.
At a glance
- Gene–disease (curated): myeloperoxidase deficiency (Moderate, GenCC)
- GWAS associations: 32 (top 4% of genes corpus-wide)
- Clinical variants (ClinVar): 101 total — 1 pathogenic, 5 likely-pathogenic
- GTEx eGene: eQTL in 9 tissues, sQTL in 0 (q < 0.05)
- Phenotypes (HPO): 14
- Drug target: yes — 1 curated mechanism-of-action drug; 19 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
- Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.99 (unconstrained)
- MANE Select transcript:
NM_000250 - Interaction hub: 3,026 STRING partners (top 2% of genes corpus-wide)
- Notable: 101 clinical variants but no curated precision-oncology (CIViC) evidence yet
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:7218 |
| Approved symbol | MPO |
| Name | myeloperoxidase |
| Location | 17q22 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000005381 |
| Ensembl biotype | protein_coding |
| OMIM | 606989 |
| Entrez | 4353 |
Gene structure
Transcript identifiers
Ensembl transcripts: 7 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay
MANE Select: ENST00000225275
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 3
ENST00000225275, ENST00000577220, ENST00000578493, ENST00000580005, ENST00000581022, ENST00000699291, ENST00000699292
RefSeq mRNA: 1 — MANE Select: NM_000250
NM_000250
CCDS: CCDS11604
Canonical transcript exons
ENST00000225275 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000480273 | 58279008 | 58279214 |
| ENSE00000480274 | 58277827 | 58278145 |
| ENSE00000480276 | 58273414 | 58273669 |
| ENSE00000739347 | 58271655 | 58271892 |
| ENSE00000739352 | 58275542 | 58275702 |
| ENSE00000739356 | 58279297 | 58279426 |
| ENSE00000739375 | 58279523 | 58279646 |
| ENSE00000739378 | 58279839 | 58280014 |
| ENSE00000739393 | 58280366 | 58280459 |
| ENSE00001151664 | 58269855 | 58270863 |
| ENSE00001151667 | 58280605 | 58280935 |
| ENSE00002445423 | 58272748 | 58272918 |
Expression profiles
Bgee: expression breadth ubiquitous, 157 present calls, max score 99.55.
FANTOM5 (CAGE): breadth broad, TPM avg 34.8139 / max 8476.8700, expressed in 296 samples.
Highest expression (Bgee): trabecular bone tissue, bone marrow cell, bone marrow, bone element, monocyte.
Genetic regulation across tissues (GTEx eQTL / sQTL)
MPO is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
9 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Whole Blood | eqtl | 4.9e-04 | -0.23 | 17:58336274:C:A |
| Artery Coronary | eqtl | 1.6e-02 | -0.52 | 17:57686805:TAGAG:T |
| Artery Tibial | eqtl | 1.9e-02 | +0.67 | 17:57530790:G:A |
| Brain Cerebellar Hemisphere | eqtl | 2.0e-02 | +0.30 | 17:58289333:C:G |
| Brain Cerebellum | eqtl | 2.1e-02 | +0.29 | 17:58306661:A:C |
| Brain Hypothalamus | eqtl | 2.1e-02 | +3.45 | 17:57737692:T:A |
| Brain Cortex | eqtl | 2.2e-02 | -1.22 | 17:57319957:C:T |
| Esophagus Mucosa | eqtl | 2.5e-02 | +1.12 | 17:57757728:G:A |
| Artery Aorta | eqtl | 4.6e-02 | -0.28 | 17:57728074:C:T |
FANTOM5 promoters
showing 10 of 33 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 167226 | 22.8882 | 67 |
| 167225 | 6.1396 | 46 |
| 167224 | 2.3700 | 32 |
| 167206 | 0.3604 | 20 |
| 167198 | 0.3227 | 154 |
| 167197 | 0.2957 | 127 |
| 167223 | 0.2001 | 19 |
| 167216 | 0.1870 | 16 |
| 167202 | 0.1811 | 15 |
| 167192 | 0.1752 | 20 |
Top tissues by expression
showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| trabecular bone tissue | UBERON:0002483 | 99.55 | gold quality |
| bone marrow cell | CL:0002092 | 99.24 | gold quality |
| bone marrow | UBERON:0002371 | 98.81 | gold quality |
| bone element | UBERON:0001474 | 96.61 | gold quality |
| monocyte | CL:0000576 | 88.14 | gold quality |
| mononuclear cell | CL:0000842 | 88.03 | gold quality |
| leukocyte | CL:0000738 | 86.92 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 83.55 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 80.89 | gold quality |
| granulocyte | CL:0000094 | 80.30 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 77.52 | silver quality |
| spleen | UBERON:0002106 | 75.99 | gold quality |
| amniotic fluid | UBERON:0000173 | 74.88 | gold quality |
| blood | UBERON:0000178 | 74.55 | gold quality |
| right lung | UBERON:0002167 | 71.54 | gold quality |
| minor salivary gland | UBERON:0001830 | 69.88 | gold quality |
| saliva-secreting gland | UBERON:0001044 | 69.57 | gold quality |
| endometrium epithelium | UBERON:0004811 | 68.42 | gold quality |
| thymus | UBERON:0002370 | 66.05 | silver quality |
| mouth mucosa | UBERON:0003729 | 66.01 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 65.73 | gold quality |
| prefrontal cortex | UBERON:0000451 | 64.41 | gold quality |
| upper lobe of lung | UBERON:0008948 | 64.11 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 63.76 | gold quality |
| gastrocnemius | UBERON:0001388 | 62.39 | gold quality |
| pancreatic ductal cell | CL:0002079 | 61.74 | silver quality |
| muscle of leg | UBERON:0001383 | 61.69 | gold quality |
| nasal cavity mucosa | UBERON:0001826 | 61.38 | gold quality |
| vena cava | UBERON:0004087 | 61.33 | gold quality |
| adenohypophysis | UBERON:0002196 | 60.50 | gold quality |
| tibia | UBERON:0000979 | 60.43 | silver quality |
| right lobe of liver | UBERON:0001114 | 60.40 | gold quality |
| right frontal lobe | UBERON:0002810 | 60.40 | gold quality |
| cingulate cortex | UBERON:0003027 | 60.34 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 60.06 | gold quality |
| pituitary gland | UBERON:0000007 | 59.16 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 59.15 | gold quality |
| frontal cortex | UBERON:0001870 | 59.01 | gold quality |
| muscle organ | UBERON:0001630 | 58.99 | gold quality |
| tonsil | UBERON:0002372 | 58.61 | gold quality |
| neocortex | UBERON:0001950 | 58.57 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 57.86 | gold quality |
| lung | UBERON:0002048 | 57.39 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 57.18 | gold quality |
| tibialis anterior | UBERON:0001385 | 57.16 | silver quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 57.03 | gold quality |
| putamen | UBERON:0001874 | 56.73 | gold quality |
| vermiform appendix | UBERON:0001154 | 56.15 | gold quality |
| parotid gland | UBERON:0001831 | 56.14 | gold quality |
| myocardium | UBERON:0002349 | 56.07 | gold quality |
| cerebral cortex | UBERON:0000956 | 55.99 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 55.78 | gold quality |
| lymph node | UBERON:0000029 | 55.52 | gold quality |
| primary visual cortex | UBERON:0002436 | 55.46 | gold quality |
| hypothalamus | UBERON:0001898 | 55.29 | gold quality |
| caudate nucleus | UBERON:0001873 | 55.24 | gold quality |
| forebrain | UBERON:0001890 | 55.22 | gold quality |
| amygdala | UBERON:0001876 | 55.21 | gold quality |
| liver | UBERON:0002107 | 55.08 | gold quality |
| telencephalon | UBERON:0001893 | 54.98 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 54.97 | gold quality |
| ileal mucosa | UBERON:0000331 | 54.93 | silver quality |
| endothelial cell | CL:0000115 | 54.91 | gold quality |
| inferior olivary complex | UBERON:0002127 | 54.89 | gold quality |
| caecum | UBERON:0001153 | 54.58 | gold quality |
| brain | UBERON:0000955 | 54.54 | gold quality |
| central nervous system | UBERON:0001017 | 54.42 | gold quality |
| nucleus accumbens | UBERON:0001882 | 54.19 | gold quality |
| substantia nigra | UBERON:0002038 | 54.17 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 54.07 | gold quality |
| cranial nerve II | UBERON:0000941 | 53.76 | gold quality |
| right atrium auricular region | UBERON:0006631 | 53.60 | gold quality |
| quadriceps femoris | UBERON:0001377 | 53.46 | gold quality |
| deltoid | UBERON:0001476 | 53.34 | gold quality |
| cardiac atrium | UBERON:0002081 | 53.29 | gold quality |
| cerebellar cortex | UBERON:0002129 | 53.27 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 53.20 | gold quality |
| midbrain | UBERON:0001891 | 52.80 | gold quality |
| cerebellum | UBERON:0002037 | 52.79 | gold quality |
| epithelium of esophagus | UBERON:0001976 | 52.74 | gold quality |
| nasal cavity epithelium | UBERON:0005384 | 52.72 | gold quality |
| heart left ventricle | UBERON:0002084 | 52.56 | gold quality |
| vastus lateralis | UBERON:0001379 | 52.41 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 52.39 | gold quality |
| heart | UBERON:0000948 | 52.36 | gold quality |
| cardiac ventricle | UBERON:0002082 | 52.34 | gold quality |
| thoracic aorta | UBERON:0001515 | 52.08 | gold quality |
| muscle tissue | UBERON:0002385 | 51.81 | gold quality |
| Ammon’s horn | UBERON:0001954 | 51.77 | gold quality |
| occipital lobe | UBERON:0002021 | 51.75 | gold quality |
| ascending aorta | UBERON:0001496 | 51.67 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 51.60 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 51.50 | gold quality |
| apex of heart | UBERON:0002098 | 51.41 | gold quality |
| temporal lobe | UBERON:0001871 | 51.26 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 51.25 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 51.14 | gold quality |
| right coronary artery | UBERON:0001625 | 51.10 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 51.07 | gold quality |
| spinal cord | UBERON:0002240 | 50.67 | gold quality |
Single-cell (SCXA)
Detected in 15 experiment(s), a significant marker in 15.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-9801 | yes | 28866.69 |
| E-MTAB-9067 | yes | 23589.16 |
| E-GEOD-89232 | yes | 18532.04 |
| E-GEOD-100618 | yes | 10251.11 |
| E-CURD-112 | yes | 9740.02 |
| E-CURD-6 | yes | 9221.90 |
| E-CURD-122 | yes | 8671.28 |
| E-MTAB-10432 | yes | 7989.05 |
| E-HCAD-6 | yes | 6014.37 |
| E-MTAB-7407 | yes | 4799.12 |
| E-MTAB-10042 | yes | 4335.14 |
| E-HCAD-4 | yes | 4312.68 |
| E-MTAB-8884 | yes | 3351.29 |
| E-GEOD-76312 | yes | 3050.07 |
| E-ANND-3 | no | 0.00 |
HPA expression
RNA tissue specificity: Tissue enriched
34 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Bone marrow | tissue | 3249.5 | high |
| Salivary gland | tissue | 9.9 | not detected |
| Thymus | tissue | 6.9 | |
| Skin 1 | tissue | 3.7 | not detected |
| Pituitary gland | tissue | 1.5 | |
| Spleen | tissue | 1.5 | not detected |
| Lymph node | tissue | 1.2 | not detected |
| Placenta | tissue | 0.9 | not detected |
| Liver | tissue | 0.7 | not detected |
| Amygdala | tissue | 0.4 | |
| Locus coeruleus | tissue | 0.4 | |
| Postcentral gyrus | tissue | 0.4 | |
| Hippocampal formation | tissue | 0.3 | |
| Urinary bladder | tissue | 0.2 | not detected |
| Epididymis | tissue | 0.2 | not detected |
| Nucleus accumbens | tissue | 0.2 | |
| Hippocampus | tissue | 0.2 | not detected |
| Adrenal gland | tissue | 0.2 | not detected |
| Appendix | tissue | 0.2 | not detected |
| Testis | tissue | 0.1 | not detected |
| Cerebral cortex | tissue | 0.1 | not detected |
| Retina | tissue | 0.1 | |
| Vagina | tissue | 0.1 | not detected |
| Rectum | tissue | 0.1 | not detected |
| Smooth muscle | tissue | 0.1 | not detected |
| Tongue | tissue | 0.1 | |
| Hypothalamus | tissue | 0.1 | |
| Thyroid gland | tissue | 0.1 | not detected |
| Lung | tissue | 0.1 | not detected |
| Small intestine | tissue | 0.1 | not detected |
| Tonsil | tissue | 0.1 | not detected |
| Periaqueductal gray | tissue | 0.1 | |
| Fallopian tube | tissue | 0.1 | not detected |
| Temporal cortex | tissue | 0.1 |
Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Area parastriata, superior (0.4), Dorsal raphe nucleus (0.4), Inferior parietal lobule (0.4), Mammillary body (0.4), Medial vestibular nucleus (0.4).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CEBPA, CEBPE, CEBPG, FOXC1, HBP1, MYC, MYCN, NR1H3, PITX3, PPARA, PPARG, RARA, RUNX1, RUNX2, RXRA, SP1, SPI1, TAL1, TFDP1, TP53, WT1, ZNF296
miRNA regulators (miRDB)
Targeting MPO by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 34 miRNAs:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-12118 | 100.00 | 65.88 | 1270 |
| HSA-MIR-4795-3P | 100.00 | 74.62 | 4024 |
| HSA-MIR-4789-3P | 99.99 | 70.75 | 2484 |
| HSA-MIR-6891-5P | 99.98 | 66.53 | 1372 |
| HSA-MIR-3173-3P | 99.98 | 66.49 | 1217 |
| HSA-MIR-95-5P | 99.89 | 72.17 | 3973 |
| HSA-MIR-6780A-5P | 99.88 | 66.69 | 2776 |
| HSA-MIR-4694-3P | 99.79 | 69.53 | 2640 |
| HSA-MIR-1273H-5P | 99.77 | 66.32 | 2471 |
| HSA-MIR-30B-3P | 99.70 | 65.76 | 2325 |
| HSA-MIR-3689A-3P | 99.70 | 65.73 | 2306 |
| HSA-MIR-3689B-3P | 99.70 | 65.71 | 2311 |
| HSA-MIR-3689C | 99.70 | 65.71 | 2311 |
| HSA-MIR-6779-5P | 99.70 | 65.76 | 2363 |
| HSA-MIR-4666B | 99.64 | 68.69 | 1282 |
| HSA-MIR-4276 | 99.56 | 67.66 | 2514 |
| HSA-MIR-451B | 99.55 | 68.28 | 1380 |
| HSA-MIR-5683 | 99.36 | 68.59 | 2083 |
| HSA-MIR-183-5P | 99.31 | 72.27 | 1164 |
| HSA-MIR-7158-5P | 99.25 | 67.95 | 796 |
| HSA-MIR-877-3P | 99.09 | 68.10 | 1637 |
| HSA-MIR-224-3P | 98.91 | 68.42 | 1815 |
| HSA-MIR-522-3P | 98.91 | 68.56 | 1817 |
| HSA-MIR-887-5P | 98.82 | 65.90 | 1347 |
| HSA-MIR-4297 | 98.77 | 66.95 | 2013 |
| HSA-MIR-4710 | 98.61 | 65.96 | 1048 |
| HSA-MIR-6827-5P | 98.46 | 64.88 | 1256 |
| HSA-MIR-6847-5P | 97.93 | 66.74 | 1808 |
| HSA-MIR-5581-5P | 97.91 | 66.50 | 965 |
| HSA-MIR-30C-1-3P | 97.80 | 66.36 | 1499 |
Functional genomics
gnomAD constraint: pLI 3.39e-16, LOEUF 0.992, missense Z 0.82 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD RMC): no regional variation along ENST00000225275 — one region, missense o/e 0.96.
Literature-anchored findings (GeneRIF, showing 40)
- Binding studies of myeloperoxidase support a model for a single common binding site for halides and thiocyanate as substrates or as inhibitors near the delta-meso carbon of the porphyrin ring in the enzyme. (PMID:11705390)
- The photoprotein pholasin as a luminescence substrate for detection of superoxide anion radicals and myeloperoxidase activity in stimulated neutrophils (PMID:11811524)
- Increased myeloperoxidase and lipid peroxide-modified protein in gynecological malignancies (LOOH-RSA, lipid peroxide-modified protein) (PMID:11813987)
- Neutrophils use MPO to initiate lipid peroxidation in whole plasma through multiple distinct diffusible substrates. Multiple endogenous diffusible substrates for myeloperoxidase in plasma are identified. (PMID:11861298)
- investigation of molecular mechanism of MPO-mediated apoptosis and caspase-3 activation (PMID:11981455)
- up-regulated by the AML1-MTG8 fusion protein, suggesting a role in the granulocytic maturation characteristic of the t(8;21) acute myelogenous leukemia (PMID:11986950)
- A common functional MPO promoter polymorphism (-463 G/A) is associated with increased incidence and clinical aspects of ANCA-associated small vessel vasculitis (PMID:12027420)
- MPO was observed to modulate the vascular signaling and vasodilatory functions of nitric oxide (NO) during acute inflammation (PMID:12089442)
- We confirm that the MPO -463 A variant affords a protective effect against lung cancer risk in smokers, which was strongest for SCLC patients. (PMID:12432558)
- Relative to subjects with the MPO G/G genotype, a significant decreased risk of lung cancer was found for carriers of G/A genotype. (PMID:12496042)
- Myeloperoxidase gene polymorphism does not decrease lung neoplasm susceptibility in caucasians. These findings are in contrast with the earlier studies suggesting a protective effect of carrying the variant A allele. (PMID:12496043)
- Lung cancer risk associated with genetic polymorphism in myeloperoxidase (-463 G/A) in a Chinese population (PMID:12515618)
- These data reveal substantial differences between the two known heme peroxidase superfamilies and reflect the dramatic differences observed in the oxidisability of substrates by the myeloperoxidase redox intermediates compound I and compound II. (PMID:12565898)
- Mediates lipid peroxidation of low-density lipoproteins as modulated by flavonoids. (PMID:12606047)
- Using mass spectrometric method, two products of myeloperoxidase, 5-chlorouracil and 5-bromouracil, were detected in neutrophil-rich human inflammatory tissue; in vitro mechanistic studies were also performed. (PMID:12707270)
- Expression of myeloperoxidase by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies against myeloperoxidase. (PMID:12773517)
- Lacrimal fluid peroxidase activity differs in men and women: the gender-related difference accentuates during ageing, probably owing to changing estrogen levels. (PMID:12792137)
- Myeloperoxidase promotor polymorphism is associated with hepatoblastoma (PMID:12800195)
- MPO polymorphism were associated with the extent of brain damage and the functional outcome rather than with the risk of developing brain infarction. (PMID:12818404)
- Myeloperoxidase (MPO) gene variation may modify the extent of advanced atherosclerotic lesions in the human aorta in early middle age. (PMID:12861032)
- In subjects with the high expression genotype of myeloperoxidase, the progression of atherosclerosis was significantly faster in the control group than in the hormone replacement therapy group, whereas in A allele carriers there were no differences (PMID:12915675)
- chemical mechanism behind the bactericidal action of the MPO-H(2)O(2)-Cl(-) system (PMID:12950060)
- in patients with acute coronary syndromes, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events; MPO may serve as both a marker and mediator of vascular inflammation (PMID:12952835)
- study shows that peroxisome proliferator-activated receptor gamma (PPARgamma) agonists strongly regulate myeloperoxidase gene expression through the Alu element repeats (PMID:14668325)
- These findings provide evidence that myeloperoxidase polymorphism is associated with coronary artery reactivity. (PMID:14730210)
- The heme-containing protein myeloperoxidase is released from stimulated polymorphonuclear leukocytes at sites of inflammation (PMID:14972011)
- Myeloperoxidase polymorphism related to cardiovascular events in coronary artery disease (PMID:15006595)
- The presence of MPO-G/G and A2M-Val/Val genotypes synergistically increased the risk of AD (OR, 25.5; 95% CI, 4.65-139.75). (PMID:15023809)
- Analysis of polymorphism in chronic renal failure patients undergoing hemodialysis. (PMID:15068388)
- the MPO/H2O2/SCN- system may have the potential to play a significant role in the oxidative modification of LDL (PMID:15203186)
- MPO G/G genotype may be one of the genetic factors influencing the progression rate of disability in multiple sclerosis patients. (PMID:15222689)
- Myeloperoxidase was detected in neurons. The increase in neuronal myeloperoxidase expression we observed in Alzheimer disease brains raises the possibility that the enzyme contributes to the oxidative stress implicated in the pathogenesis of the disorder (PMID:15255951)
- MPO appears to be an important modulator of vasomotor function in inflammatory vascular disease (PMID:15304260)
- Insights into mechanisms for inactivating MPO and the novel mode of oxygen binding to the hemoprotein may provide important clues toward understanding the catalytic action of MPO. (PMID:15350145)
- involvement of MPO in the antituberculous, immunological response implies its connection with TNF-alpha and IL-12 activation. (PMID:15379210)
- May represent an important pathway in diabetes complications and a new mechanism in phagocyte- and systemic infection-induced exacerbation of diabetic vascular diseases. (PMID:15504976)
- Mutations of the gene associated with MPO deficiency in Italian patients. (PMID:15507752)
- Mutations of the gene associated with MPO deficiency in Japanese patients. (PMID:15507753)
- Post-translational processing of pro-MPO, MPO secretion and storage, and the role of MPO in signal transduction in granulocytes. (PMID:15507754)
- Myeloperoxidase (MPO)-specific antibodies against neutrophils, anti-neutrophil cytoplasmic antibodies (MPO-ANCA) is involved in the development of vasculitis. (PMID:15507759)
Cross-species orthologs
11 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | epx | ENSDARG00000012535 |
| mus_musculus | Mpo | ENSMUSG00000009350 |
| rattus_norvegicus | Mpo | ENSRNOG00000008310 |
| drosophila_melanogaster | Pxd | FBGN0004577 |
| drosophila_melanogaster | Pxn | FBGN0011828 |
| drosophila_melanogaster | CG4009 | FBGN0038469 |
| drosophila_melanogaster | cysu | FBGN0038511 |
| caenorhabditis_elegans | WBGENE00004256 | |
| caenorhabditis_elegans | WBGENE00004257 | |
| caenorhabditis_elegans | WBGENE00016700 | |
| caenorhabditis_elegans | WBGENE00019613 |
Paralogs (5): TPO (ENSG00000115705), EPX (ENSG00000121053), PXDN (ENSG00000130508), PXDNL (ENSG00000147485), LPO (ENSG00000167419)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:97137) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| abnormal neutrophil physiology | 3 |
| atherosclerotic lesions | 2 |
| increased susceptibility to fungal infection | 2 |
| increased susceptibility to induced morbidity/mortality | 2 |
| increased monocyte cell number | 1 |
| decreased inflammatory response | 1 |
| abnormal muscle fiber morphology | 1 |
| increased susceptibility to experimental autoimmune encephalomyelitis | 1 |
| sepsis | 1 |
| abnormal response to injury | 1 |
| abnormal metabolism | 1 |
| increased physiological sensitivity to xenobiotic | 1 |
Additional cross-species homologs
Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Bubalus bubalis | A5JUY8 | 99.4% | Diamond |
| Bos taurus | P80025 | 99.4% | Diamond |
| Capra hircus | A0A452E9Y6 | 95.1% | Diamond |
| Oryctolagus cuniculus | O02768 | 90.9% | Diamond |
| Equus caballus | O19183 | 90.9% | Diamond |
| Cavia porcellus | P70682 | 90.2% | Diamond |
| Caenorhabditis briggsae | A8WQH2 | 87.3% | Diamond |
| Mesocricetus auratus | Q8R481 | 84.6% | Diamond |
| Gallus gallus | P27607 | 82.1% | Diamond |
| Xenopus tropicalis | A4IGL7 | 81.7% | Diamond |
| Canis lupus familiaris | Q8HYB7 | 74.2% | Diamond |
| Sus scrofa | P09933 | 73.3% | Diamond |
| Anopheles gambiae | Q7QH73 | 51.4% | Diamond |
| Aedes aegypti | P82600 | 49.3% | Diamond |
| Lottia gigantea | B3A0P3 | 45.9% | Diamond |
| Pinctada margaritifera | H2A0M7 | 36.6% | Diamond |
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| MIR4736 | ncRNA | 100616220 |
| MIR142HG | ncRNA | 123466215 |
| HSF5 | protein-coding | 124535 |
| LPO | protein-coding | 4025 |
| MIR142 | ncRNA | 406934 |
| RNF43 | protein-coding | 54894 |
| SUPT4H1 | protein-coding | 6827 |
| MTMR4 | protein-coding | 9110 |
| TSPOAP1 | protein-coding | 9256 |
| MKS1 | protein-coding | 54903 |
| EPX | protein-coding | 8288 |
| TSPOAP1-AS1 | ncRNA | 100506779 |
| OR4D2 | protein-coding | 124538 |
Protein
Protein identifiers
Myeloperoxidase — P05164 (reviewed: P05164)
All UniProt accessions (3): P05164, A0A8V8TPE5, J3QSF7
UniProt curated annotations — full annotation on UniProt →
Function. Peroxidase that plays a central role in the host defense system of polymorphonuclear leukocytes by mediating both (1) formation of neutrophil extracellular trap (NETs) and (2) microbicidal activity. Promotes NET formation by mediating chromatin disassembly: translocates to the nucleus and specifically binds to nucleosomes, both as monomer and homodimer, leading to nucleosome unstacking and initial chromatin decondensation. Homodimers clash with one end of the nucleosomal DNA, leading to DNA unwrapping, initiating complete disassembly of nucleosomes and chromatin transformation into NETs in an ATP-independent manner. NETs, which are mainly composed of DNA fibers and globular proteins, are then extruded into the extracellular space by neutrophils to trap pathogens and release antimicrobial proteins to destroy them. Participates to the microbicidal activity against a wide range of organisms by acting as a peroxidase that catalyzes the formation of oxidants in presence of hydrogen peroxide. Mediates the formation of hypohalous acids, mainly hypochlorous acid (HOCl) in physiologic situations, that greatly enhance polymorphonuclear leukocyte microbicidal activity. In addition to hypochlorous acid, catalyzes formation of hypobromous acid (HOBr), hypoiodous acid (HOI) and hypothiocyanous acid (HOSCN). Also catalyzes oxidation of nitrite into the highly reactive nitrogen dioxide radical. Formation of oxidants are widely believed to be responsible for much of the anti-bactericidal activity of neutrophils. Oxidants, such as hypochlorous acid or nitrogen dioxide radical, can also oxidize amino acid residues on proteins and generate chlorination and nitration post-translational modifications, respectively. Chlorination and nitration of the lipid-free form of APOA1 impairs cholesterol transport. Superoxides generated by MPO can also promote dioxygenation of tryptophan residues on proteins. Also able to oxidize melatonin into N1-acetyl-N2-formyl-5-methoxykynuramine either in presence of hydrogen peroxide or superoxide. Oxidizes urate into 5-hydroxyisourate. Functions as a nitric oxide (NO) oxidase during inflammation, by catalytically consuming NO, impairing NO’s ability to maintain vascular tone and function. May also mediate 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. Light chain of the mature myeloperoxidase. Heavy chain of the mature myeloperoxidase. (Microbial infection) The peroxidase activity is inhibited by S.aureus peroxidase inhibitor SPIN that blocks substrate access to the catalytic heme.
Subunit / interactions. Mature myeloperoxidase is a homodimer; disulfide-linked. Each monomer is composed of myeloperoxidase heavy chain and myeloperoxidase light chain. Interacts with CP (ceruloplasmin); inhibiting the peroxidase activity of MPO. Found in a complex with CP and LTF; protects CP antioxidant properties by MPO. Mature myeloperoxidase is a homodimer; disulfide-linked. Each monomer is composed of myeloperoxidase heavy chain and myeloperoxidase light chain. Mature myeloperoxidase is a homodimer; disulfide-linked. Each monomer is composed of myeloperoxidase heavy chain and myeloperoxidase light chain.
Subcellular location. Lysosome. Cytolytic granule. Cytoplasmic vesicle. Phagosome. Secreted. Nucleus. Chromosome.
Tissue specificity. Specifically expressed in neutrophils and monocytes.
Post-translational modifications. Mature myeloperoxidase is a homodimer linked by disulfide bond, with each monomer composed of a heavy and light chain. Myeloperoxidase encompasses a series of critical proteolytic processing steps during maturation: after cotranslational cleavage of the signal peptide and N-linked glycosylation followed by limited deglucosylation, myeloperoxidase acquires heme in the endoplasmic reticulum (ER) to form the 84 kDa myeloperoxidase (also named promyeloperoxidase). A proconvertase then eliminates the propeptide region (49-164) in a post-ER compartment producing an intermediate species that is subsequently processed by cysteine proteases to the light chain and heavy chain followed by homodimerization. Myeloperoxidase monomers are linked by an interchain disulfide bond at Cys-319. During maturation, the 84 kDa myeloperoxidase (also named promyeloperoxidase) precursor contains a disulfide bond between Cys-158 and Cys-319 that prevents homodimerization. N-glycosylated; all sites contain a fraction of paucimannose-type glycans. Asn-323 contains phosphorylated (probably mannose-6-phosphate) and paucimannose-type N-glycans. Asn-355 and Asn-391 primarily show high-mannose or paucimannose glycan-types without core-fucosylation, but are partially deglucosylated during maturation of the protein. Truncation of N-glycans leads to increased myeloperoxidase activity. Asn-483 contains paucimannose-type glycans, with abundant signals of sialylated complex glycans. Asn-729 only contains paucimannose-type glycans.
Disease relevance. Myeloperoxidase deficiency (MPOD) [MIM:254600] A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. The disease is caused by variants affecting the gene represented in this entry.
Activity regulation. The peroxidase activity is inhibited by CP (ceruloplasmin). The peroxidase activity is inhibited by 2-thioxanthines which form a covalent attachment with the heme group. Inhibited by 3-(2-ethoxypropyl)- 2-thioxo-2,3-dihydro-1H-purin-6(9H)-one, a derivative of 2-thioxanthine that couples with the heme group. Specifically inhibited by aromatic hydroxamates, such as trifluoromethyl-substituted aromatic hydroxamate HX1.
Cofactor. Binds 1 Ca(2+) ion per monomer. Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per monomer.
Similarity. Belongs to the peroxidase family. XPO subfamily.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P05164-1 | H17, B | yes |
| P05164-2 | H14 | |
| P05164-3 | H7, A |
RefSeq proteins (1): NP_000241* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR010255 | Haem_peroxidase_sf | Homologous_superfamily |
| IPR019791 | Haem_peroxidase_animal | Family |
| IPR037120 | Haem_peroxidase_sf_animal | Homologous_superfamily |
Pfam: PF03098
Enzyme classification (BRENDA)
- EC 1.11.2.2 — myeloperoxidase (BRENDA: 9 organisms, 109 substrates, 246 inhibitors, 35 Km, 33 kcat entries)
Substrate kinetics (BRENDA)
21 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| 1-ACETYL-4-(METHYLSULFANYL)BENZENE | 0.016–0.039 | 2 |
| 1-CHLORO-4-(METHYLSULFANYL)BENZENE | 0.027–0.067 | 2 |
| 1-METHOXY-4-(METHYLSULFANYL)BENZENE | 0.012–0.03 | 2 |
| 1-METHYL-4-(METHYLSULFANYL)BENZENE | 0.032–0.04 | 2 |
| 1-NITRO-4-(METHYLSULFANYL)BENZENE | 0.066–0.076 | 2 |
| 3,4-DIHYDROXYPHENYLACETIC ACID | 0.52–21.9 | 2 |
| 4-(METHYLSULFANYL)ANILINE | 0.057–0.104 | 2 |
| BENZOTHIOPHENE | 0.072–0.081 | 2 |
| BENZYL METHYL SULFIDE | 0.05–0.083 | 2 |
| CATECHOL | 1.84–21.1 | 2 |
| DOPAMINE | 0.64–136.3 | 2 |
| H2O2 | 0.03–0.07 | 2 |
| PHENYL PROPAN-2-YL SULFIDE | 0.026–0.041 | 2 |
| SCN- | 0.25–0.29 | 2 |
| THIOANISOLE | 0.018–0.02 | 2 |
Catalyzed reactions (Rhea)
- chloride + H2O2 + H(+) = hypochlorous acid + H2O (RHEA:28218)
- bromide + H2O2 = hypobromite + H2O (RHEA:66016)
- thiocyanate + H2O2 + H(+) = hypothiocyanous acid + H2O (RHEA:69416)
- iodide + H2O2 = hypoiodite + H2O (RHEA:69420)
UniProt features (124 total): helix 38, strand 21, turn 11, binding site 9, disulfide bond 8, sequence variant 8, chain 7, mutagenesis site 7, glycosylation site 6, site 2, splice variant 2, signal peptide 1, modified residue 1, propeptide 1, sequence conflict 1, active site 1
Structure
Experimental structures (PDB)
showing 30 of 49 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 5MFA | Crystal structure of human promyeloperoxidase (proMPO) | X-RAY DIFFRACTION | 1.2 |
| 5FIW | CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE AT 1.7 ANGSTROMS RESOLUTION | X-RAY DIFFRACTION | 1.7 |
| 1D2V | CRYSTAL STRUCTURE OF BROMIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5 | X-RAY DIFFRACTION | 1.75 |
| 1CXP | CRYOGENIC CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C | X-RAY DIFFRACTION | 1.8 |
| 1DNU | STRUCTURAL ANALYSES OF HUMAN MYELOPEROXIDASE-THIOCYANATE COMPLEX | X-RAY DIFFRACTION | 1.85 |
| 1D5L | CRYSTAL STRUCTURE OF CYANIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5 | X-RAY DIFFRACTION | 1.9 |
| 1D7W | CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C COMPLEXED WITH CYANIDE AND BROMIDE … | X-RAY DIFFRACTION | 1.9 |
| 1DNW | HUMAN MYELOPEROXIDASE-CYANIDE-THIOCYANATE COMPLEX | X-RAY DIFFRACTION | 1.9 |
| 9QEX | Structure of native leukocyte myeloperoxidase in complex with a truncated version of the … | X-RAY DIFFRACTION | 1.9 |
| 4C1M | Myeloperoxidase in complex with the revesible inhibitor HX1 | X-RAY DIFFRACTION | 2 |
| 4DL1 | Crystal Structure of human Myeloperoxidase with covalent thioxanthine analog | X-RAY DIFFRACTION | 2 |
| 9QE3 | Structure of native leukocyte myeloperoxidase in complex with a truncated version of the … | X-RAY DIFFRACTION | 2.06 |
| 6WY7 | CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH Compound-41 A.K.A … | X-RAY DIFFRACTION | 2.09 |
| 7NI3 | CRYSTAL STRUCTURE OF NATIVE HUMAN MYELOPEROXIDASE IN COMPLEX WITH CPD 3 | X-RAY DIFFRACTION | 2.1 |
| 7NI1 | CRYSTAL STRUCTURE OF NATIVE HUMAN MYELOPEROXIDASE IN COMPLEX WITH CPD 9 | X-RAY DIFFRACTION | 2.11 |
| 7QZR | Structure of native leukocyte myeloperoxidase in complex with the Staphyloccal Peroxidase … | X-RAY DIFFRACTION | 2.18 |
| 9QJO | Structure of native leukocyte myeloperoxidase in complex with the Staphylococcal … | X-RAY DIFFRACTION | 2.18 |
| 9QGA | Structure of native leukocyte myeloperoxidase in complex with a truncated version of the … | X-RAY DIFFRACTION | 2.21 |
| 6WXZ | CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH Compound-29 A.K.A … | X-RAY DIFFRACTION | 2.23 |
| 1MHL | CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C CRYSTALLIZED IN SPACE GROUP P2(1) AT … | X-RAY DIFFRACTION | 2.25 |
| 7LAN | CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH COMPOUND-30 AKA … | X-RAY DIFFRACTION | 2.28 |
| 7Z53 | Structure of native leukocyte myeloperoxidase in complex with a truncated version (SPIN … | X-RAY DIFFRACTION | 2.28 |
| 6AZP | A Structurally Dynamic N-terminal Region Drives Function of the Staphylococcal Peroxidase … | X-RAY DIFFRACTION | 2.29 |
| 3ZS0 | Human Myeloperoxidase inactivated by TX2 | X-RAY DIFFRACTION | 2.3 |
| 5WDJ | CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH COMPOUND-6 AKA … | X-RAY DIFFRACTION | 2.4 |
| 5UZU | Immune evasion by a Staphylococcal Peroxidase Inhibitor that blocks myeloperoxidase | X-RAY DIFFRACTION | 2.4 |
| 6BMT | Crystal Structure of a Recombinant form of Human Myeloperoxidase Bound to an Inhibitor … | X-RAY DIFFRACTION | 2.4 |
| 9SDS | Structure of native leukocyte myeloperoxidase in complex with a truncated version of the … | X-RAY DIFFRACTION | 2.49 |
| 6WYD | CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH Compound-12 (AKA … | X-RAY DIFFRACTION | 2.55 |
| 3ZS1 | Human Myeloperoxidase inactivated by TX5 | X-RAY DIFFRACTION | 2.6 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P05164-F1 | 89.55 | 0.76 |
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Candidate cardiovascular disease genes, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): vesicles; nucleoplasm
Antibody reliability (HPA): IH enhanced · IF supported
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (3)
| Position | Role |
|---|---|
| 405 | transition state stabilizer |
| 409–410 | cleavage; by autolysis |
| 261 | proton acceptor |
Ligand- & substrate-binding residues (9)
| Position | Role |
|---|---|
| 260 | heme b |
| 262 | Ca(2+) |
| 334 | Ca(2+) |
| 336 | Ca(2+) |
| 338 | Ca(2+) |
| 340 | Ca(2+) |
| 408 | heme b |
| 409 | heme b |
| 502 | heme b |
Post-translational modifications (1)
| Type | Positions |
|---|---|
| Cysteine sulfenic acid (-soh) | 316 |
Disulfide bonds (8)
| Type | Positions |
|---|---|
| Disulfide bond | 158–319, 167–180, 281–291, 285–309, 387–398, 606–663, 704–730 |
| Interchain | 319 |
Glycosylation sites (6)
| Type | Positions |
|---|---|
| N-linked (glcnac…) asparagine | 139, 323, 355, 391, 483, 729 |
Mutagenesis-validated functional residues (7)
| Position | Phenotype |
|---|---|
| 129–136 | prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. |
| 129 | prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. decreased peroxidase activity. |
| 131 | prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. does not affect the peroxidase activity. |
| 135 | prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. does not affect the peroxidase activity. |
| 136 | prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. does not affect the peroxidase activity. |
| 260 | impaired binding to heme b, leading to decreased peroxidase activity. |
| 587 | abolished interaction with h-502, leading to abolished peroxidase activity. |
Function
Pathways and Gene Ontology
Reactome pathways
2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
5 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-8941413 | Events associated with phagocytolytic activity of PMN cells | curated |
| R-HSA-6798695 | Neutrophil degranulation | curated |
| R-HSA-168256 | Immune System | — |
| R-HSA-168249 | Innate Immune System | — |
| R-HSA-1222556 | ROS and RNS production in phagocytes | — |
MSigDB gene sets: 270 (showing top):
VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_93, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_FOOD, CHEOK_RESPONSE_TO_HD_MTX_UP, MODULE_16, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MODULE_118, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MODULE_75, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE
GO Biological Process (17): nucleosome disassembly (GO:0006337), defense response (GO:0006952), response to oxidative stress (GO:0006979), response to mechanical stimulus (GO:0009612), response to food (GO:0032094), response to lipopolysaccharide (GO:0032496), low-density lipoprotein particle remodeling (GO:0034374), defense response to bacterium (GO:0042742), hydrogen peroxide catabolic process (GO:0042744), negative regulation of apoptotic process (GO:0043066), neutrophil-mediated killing of symbiont cell (GO:0070943), neutrophil-mediated killing of bacterium (GO:0070944), neutrophil-mediated killing of fungus (GO:0070947), neutrophil extracellular trap formation (GO:0140645), response to gold nanoparticle (GO:1990268), cellular oxidant detoxification (GO:0098869), positive regulation of cholesterol import (GO:1904109)
GO Molecular Function (9): chromatin binding (GO:0003682), peroxidase activity (GO:0004601), heparin binding (GO:0008201), heme binding (GO:0020037), nucleosome binding (GO:0031491), metal ion binding (GO:0046872), protein-containing complex destabilizing activity (GO:0140776), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)
GO Cellular Component (10): extracellular region (GO:0005576), nucleus (GO:0005634), lysosome (GO:0005764), secretory granule (GO:0030141), azurophil granule lumen (GO:0035578), azurophil granule (GO:0042582), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), phagocytic vesicle lumen (GO:0097013), neutrophil extracellular trap (GO:0140644)
Reactome top-level categories
3 top-level categories:
| Category | Pathways |
|---|---|
| Innate Immune System | 2 |
| ROS and RNS production in phagocytes | 1 |
| Immune System | 1 |
GO top-level categories
55 GO namespaces:
| Category | Terms |
|---|---|
| response to stress | 2 |
| neutrophil-mediated killing of symbiont cell | 2 |
| binding | 2 |
| protein-DNA complex disassembly | 1 |
| nucleosome organization | 1 |
| response to external stimulus | 1 |
| response to abiotic stimulus | 1 |
| response to nutrient levels | 1 |
| response to chemical | 1 |
| response to molecule of bacterial origin | 1 |
| response to lipid | 1 |
| response to oxygen-containing compound | 1 |
| plasma lipoprotein particle remodeling | 1 |
| defense response | 1 |
| response to bacterium | 1 |
| catabolic process | 1 |
| hydrogen peroxide metabolic process | 1 |
| apoptotic process | 1 |
| regulation of apoptotic process | 1 |
| negative regulation of programmed cell death | 1 |
| killing of cells of another organism | 1 |
| neutrophil mediated cytotoxicity | 1 |
| defense response to bacterium | 1 |
| defense response to fungus | 1 |
| cellular component assembly | 1 |
| response to transition metal nanoparticle | 1 |
| cellular detoxification | 1 |
| positive regulation of cholesterol transport | 1 |
| regulation of cholesterol import | 1 |
| cholesterol import | 1 |
| antioxidant activity | 1 |
| oxidoreductase activity, acting on peroxide as acceptor | 1 |
| glycosaminoglycan binding | 1 |
| sulfur compound binding | 1 |
| tetrapyrrole binding | 1 |
| chromatin binding | 1 |
| protein-containing complex binding | 1 |
| cation binding | 1 |
| molecular_function | 1 |
| catalytic activity | 1 |
| cellular anatomical structure | 1 |
| intracellular membrane-bounded organelle | 1 |
| lytic vacuole | 1 |
| endomembrane system | 1 |
| secretory vesicle | 1 |
| vacuolar lumen | 1 |
| secretory granule lumen | 1 |
| azurophil granule | 1 |
| primary lysosome | 1 |
| secretory granule | 1 |
| endocytic vesicle | 1 |
| extracellular vesicle | 1 |
| phagocytic vesicle | 1 |
| endocytic vesicle lumen | 1 |
| extracellular membraneless organelle | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).
17 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| hydrogen peroxide catabolic process | BP | direct assay |
| low-density lipoprotein particle remodeling | BP | direct assay |
| neutrophil extracellular trap formation | BP | direct assay |
| neutrophil-mediated killing of bacterium | BP | direct assay |
| neutrophil-mediated killing of fungus | BP | direct assay |
| neutrophil-mediated killing of symbiont cell | BP | direct assay |
| nucleosome disassembly | BP | direct assay |
| azurophil granule | CC | direct assay |
| extracellular exosome | CC | high-throughput assay |
| neutrophil extracellular trap | CC | direct assay |
| nucleus | CC | direct assay |
| phagocytic vesicle | CC | direct assay |
| secretory granule | CC | direct assay |
| heparin binding | MF | direct assay |
| nucleosome binding | MF | direct assay |
| peroxidase activity | MF | direct assay |
| protein-containing complex destabilizing activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 3,026 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| MPO | ELANE | P08246 | 936 |
| MPO | PRTN3 | P15637 | 913 |
| MPO | IL6 | P05231 | 865 |
| MPO | CTSG | P08311 | 861 |
| MPO | LTF | P02788 | 841 |
| MPO | IL1B | P01584 | 840 |
| MPO | IL10 | P22301 | 816 |
| MPO | TNF | P01375 | 805 |
| MPO | CRP | P02741 | 797 |
| MPO | CD68 | P34810 | 792 |
| MPO | F5H3C5 | F5H3C5 | 783 |
| MPO | IFNG | P01579 | 767 |
| MPO | PADI4 | Q9UM07 | 757 |
| MPO | CSF3 | P09919 | 746 |
| MPO | TLR4 | O00206 | 744 |
IntAct
Human interaction partners of MPO in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
16 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| CALR | direct interaction | 0.580 | 3 |
| STUB1 | physical association | 0.560 | 3 |
| CFP | direct interaction | 0.540 | 1 |
| EGFL8 | association | 0.530 | 1 |
| C3 | physical association | 0.400 | 2 |
| C9 | physical association | 0.400 | 1 |
| CCDC47 | physical association | 0.400 | 1 |
| GYPA | physical association | 0.400 | 1 |
| GYPB | physical association | 0.400 | 1 |
| HNRNPK | physical association | 0.400 | 1 |
| SLC4A1 | physical association | 0.400 | 1 |
| C9orf85 | association | 0.350 | 1 |
| HS1BP3 | association | 0.350 | 1 |
| MAEA | association | 0.350 | 1 |
| MNAT1 | association | 0.350 | 1 |
| PTEN | proximity | 0.270 | 1 |
BioGRID (60 interactions; top human partners by supporting records): ICE2 (Affinity Capture-MS; 3 records), APCDD1 (Affinity Capture-MS; 2 records), FRMD1 (Affinity Capture-MS; 2 records), PLB1 (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS), ALB (Co-fractionation), CAT (Co-fractionation), CCR1 (Affinity Capture-MS), CEBPA (Protein-peptide), CLCN2 (Affinity Capture-MS), CYP3A43 (Affinity Capture-MS), EGFL8 (Affinity Capture-MS), ELANE (Co-fractionation), ERO1L (Affinity Capture-MS), ESR2 (Affinity Capture-MS)
SIGNOR signaling
3 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| KRT1 | “up-regulates quantity” | MPO | binding |
| MPO | “down-regulates activity” | APOA1 | oxidation |
| MPO | “up-regulates activity” | MPO-ANCA | binding |
Protein complexes (CORUM) (2)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
2 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| CP-LTF-MPO complex | 3 | LTF, MPO, CP |
| CP-MPO complex | 2 | CP, MPO |
Disease & clinical
Genetic variants
Variant evidence for MPO: 101 ClinVar records (6 pathogenic / likely pathogenic); 32 GWAS associations. Per-variant detail is on Sugi Variant.
ClinVar
101 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 5 |
| Uncertain significance | 61 |
| Likely benign | 22 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (6)
Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.
| Variant ID | HGVS | Classification | Review | Submitters |
|---|---|---|---|---|
| 452644 | NM_000250.2(MPO):c.1281del (p.Thr428fs) | Likely pathogenic | criteria provided, multiple submitters, no conflicts | 3 |
| 4845803 | NM_000250.2(MPO):c.1805G>A (p.Trp602Ter) | Likely pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 4857469 | NM_000250.2(MPO):c.625_626del (p.Leu209fs) | Pathogenic | criteria provided, single submitter | 1 |
| 3779889 | NM_000250.2(MPO):c.817dup (p.Ala273fs) | Likely pathogenic | criteria provided, single submitter | 1 |
| 3893371 | NM_000250.2(MPO):c.760_764del (p.Gln254fs) | Likely pathogenic | criteria provided, single submitter | 1 |
| 3351076 | NM_000250.2(MPO):c.604dup (p.Glu202fs) | Likely pathogenic | no assertion criteria provided | 1 |
Per-variant reference — Sugi Variant
Explore MPO’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 928):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 17:58271893–58271894 | acceptor_loss | 1.0000 | 2 |
| 17:58272746–58272747 | donor_loss | 1.0000 | 5 |
| 17:58272919–58272920 | acceptor_loss | 1.0000 | 5 |
| 17:58275704 | acceptor_gain | 1.0000 | |
| 17:58277826 | donor_loss | 1.0000 | 2 |
| 17:58279006–58279007 | donor_loss | 1.0000 | 3 |
| 17:58279041 | donor_gain | 1.0000 | |
| 17:58279215–58279216 | acceptor_loss | 1.0000 | 6 |
| 17:58279537 | donor_gain | 1.0000 | |
| 17:58279647–58279648 | acceptor_loss | 1.0000 | 5 |
AlphaMissense
1,810 missense substitutions predicted likely pathogenic (of 4,867 scored), across 442 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| D582 | 8 | 0.995 | 0.997 |
| H261 | 8 | 0.993 | 0.998 |
| D300 | 8 | 0.985 | 0.993 |
| H502 | 8 | 0.985 | 0.993 |
| D403 | 8 | 0.984 | 0.997 |
| H423 | 8 | 0.984 | 0.990 |
| D338 | 8 | 0.981 | 0.992 |
| F573 | 8 | 0.977 | 0.997 |
| D676 | 8 | 0.974 | 0.990 |
| D262 | 8 | 0.972 | 0.992 |
| D593 | 8 | 0.971 | 0.997 |
| F494 | 8 | 0.961 | 0.997 |
| D641 | 8 | 0.957 | 0.989 |
| H594 | 8 | 0.954 | 0.991 |
| D260 | 8 | 0.950 | 0.988 |
| F686 | 8 | 0.940 | 0.986 |
| F718 | 8 | 0.936 | 0.982 |
| F399 | 8 | 0.933 | 0.985 |
| D245 | 8 | 0.929 | 0.953 |
| N424 | 8 | 0.923 | 0.989 |
HPA cancer prognostics
RNA cancer specificity: Cancer enhanced (Stomach Adenocarcinoma)
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
1 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Stomach Adenocarcinoma (TCGA) | unfavorable | 0.000787 |
Disease associations
OMIM: gene MIM:606989 | disease phenotypes: MIM:254600
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| myeloperoxidase deficiency | Moderate | Autosomal recessive |
Genomics England panels (PanelApp)
Clinical diagnostic gene panels including this gene (2 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.
2 panels:
| Panel | Rating |
|---|---|
| COVID-19 research | green |
| Primary immunodeficiency or monogenic inflammatory bowel disease | amber |
Mondo (1): myeloperoxidase deficiency (MONDO:0009694)
Orphanet (1): Myeloperoxidase deficiency (Orphanet:2587)
HPO phenotypes
14 phenotypes (HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000726 | Dementia |
| HP:0001300 | Parkinsonism |
| HP:0001871 | Abnormality of blood and blood-forming tissues |
| HP:0001939 | Abnormality of metabolism/homeostasis |
| HP:0002185 | Neurofibrillary tangles |
| HP:0002423 | Long-tract sign |
| HP:0002511 | Alzheimer disease |
| HP:0002715 | Abnormality of the immune system |
| HP:0003581 | Adult onset |
| HP:0410054 | Decreased circulating GABA concentration |
| HP:6000375 | Reduced neutrophil myeloperoxidase activity |
| HP:6000513 | Diminished neutrophil myeloperoxidase activity |
GWAS associations
showing 30 of 32 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST90002394_402 | Monocyte percentage of white cells | 7e-71 |
| GCST004609_148 | Monocyte percentage of white cells | 4e-63 |
| GCST004608_200 | Granulocyte percentage of myeloid white cells | 9e-57 |
| GCST90002393_199 | Monocyte count | 9e-50 |
| GCST004625_244 | Monocyte count | 8e-41 |
| GCST90002394_399 | Monocyte percentage of white cells | 2e-31 |
| GCST90002379_85 | Basophil count | 3e-30 |
| GCST90002399_332 | Neutrophil percentage of white cells | 5e-30 |
| GCST90002380_104 | Basophil percentage of white cells | 5e-26 |
| GCST90002379_84 | Basophil count | 3e-23 |
| GCST004620_114 | Sum basophil neutrophil counts | 2e-18 |
| GCST004629_107 | Neutrophil count | 2e-18 |
| GCST90002398_393 | Neutrophil count | 9e-18 |
| GCST004613_26 | Sum neutrophil eosinophil counts | 3e-17 |
| GCST90002394_401 | Monocyte percentage of white cells | 3e-17 |
| GCST004626_12 | Myeloid white cell count | 4e-17 |
| GCST004614_11 | Granulocyte count | 6e-17 |
| GCST90002407_635 | White blood cell count | 2e-16 |
| GCST009731_51 | Blood protein levels in cardiovascular risk | 5e-16 |
| GCST004633_120 | Neutrophil percentage of white cells | 2e-15 |
| GCST004610_25 | White blood cell count | 9e-13 |
| GCST90002389_260 | Lymphocyte percentage of white cells | 1e-12 |
| GCST90002393_197 | Monocyte count | 5e-12 |
| GCST90002399_334 | Neutrophil percentage of white cells | 2e-11 |
| GCST90002398_395 | Neutrophil count | 2e-10 |
| GCST90002394_400 | Monocyte percentage of white cells | 3e-10 |
| GCST90002380_103 | Basophil percentage of white cells | 7e-10 |
| GCST90002393_198 | Monocyte count | 2e-9 |
| GCST90002399_333 | Neutrophil percentage of white cells | 2e-9 |
| GCST001980_2 | Circulating myeloperoxidase levels (plasma) | 4e-9 |
EFO canonical traits (from GWAS)
12 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0005243 | myeloperoxidase measurement |
| EFO:0004713 | FEV/FVC ratio |
| EFO:0007997 | granulocyte percentage of myeloid white cells |
| EFO:0007989 | monocyte percentage of leukocytes |
| EFO:0004833 | neutrophil count |
| EFO:0004842 | eosinophil count |
| EFO:0007987 | granulocyte count |
| EFO:0005090 | basophil count |
| EFO:0005091 | monocyte count |
| EFO:0007990 | neutrophil percentage of leukocytes |
| EFO:0007992 | basophil percentage of leukocytes |
| EFO:0007993 | lymphocyte percentage of leukocytes |
MeSH disease descriptors
1 disease descriptors:
| Descriptor | Name | Tree numbers |
|---|---|---|
| C562864 | Myeloperoxidase Deficiency *(supp.)* |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL2439 (SINGLE PROTEIN)
Drugs by curated mechanism of action (ChEMBL)
Drugs whose curated ChEMBL mechanism of action targets the MPO protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.
1 curated-mechanism drugs:
| Drug | Modality | Max phase |
|---|---|---|
| VERDIPERSTAT | Small molecule | 3 |
Molecules with ChEMBL bioactivity
Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,179,323 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
19 molecules by phase:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1043 | DAPSONE | 4 | 65,329 |
| CHEMBL276832 | HYDRALAZINE | 4 | 23,974 |
| CHEMBL64 | ISONIAZID | 4 | 145,747 |
| CHEMBL686 | MEFENAMIC ACID | 4 | 62,458 |
| CHEMBL45 | MELATONIN | 4 | 57,288 |
| CHEMBL86 | METOCLOPRAMIDE | 4 | 38,126 |
| CHEMBL56367 | NIMESULIDE | 4 | 25,616 |
| CHEMBL490 | PAROXETINE | 4 | 46,771 |
| CHEMBL1518 | PROPYLTHIOURACIL | 4 | 15,154 |
| CHEMBL54976 | TRYPTOPHAN | 4 | 555,773 |
| CHEMBL4297594 | VERDIPERSTAT | 3 | 141 |
| CHEMBL50 | QUERCETIN | 3 | 75,572 |
| CHEMBL23588 | FLUFENAMIC ACID | 2 | 35,023 |
| CHEMBL2105120 | FTIVAZIDE | 2 | 118 |
| CHEMBL267044 | LEVOSULPIRIDE | 2 | 4,291 |
| CHEMBL5095218 | MITIPERSTAT | 2 | 57 |
| CHEMBL1232461 | MOLIBRESIB | 2 | 1,601 |
| CHEMBL150 | KAEMPFEROL | 1 | 26,246 |
| CHEMBL3633460 | PF-06282999 | 1 | 38 |
PharmGKB: 1 entry (CPIC guideline: no)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — Oxidoreductases
Most potent curated ligand interactions (6 total), top 6:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| mitiperstat | Inhibition | 9.15 | pIC50 |
| compound 28 [PMID: 28671460] | Inhibition | 7.36 | pIC50 |
| aminopyridine 2 | Inhibition | 6.8 | pIC50 |
| AZD5904 | Inhibition | 6.7 | pIC50 |
| PF-06282999 | Inhibition | 6.5 | pKi |
| verdiperstat | Inhibition | 6.2 | pIC50 |
Binding affinities (BindingDB)
621 measured of 730 human assays (753 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 1-[[2-[(2S,4R)-4-(difluoromethyl)piperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 1 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 2-sulfanylidene-1-[[2-[(2R,4S)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 1.5 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| CHEMBL4763667 | IC50 | 2 nM | |
| 1-[[2-[(2S)-piperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 2 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 2-sulfanylidene-3-[[2-[(2S,4R)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-5,7,8,9-tetrahydro-4H-purin-6-one | IC50 | 2 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 1-[[2-[(2S)-4,4-difluoropiperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 2.7 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 2-sulfanylidene-3-[[2-[(2R,4R)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-5,7,8,9-tetrahydro-4H-purin-6-one | IC50 | 2.7 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 1-[[2-[(2S)-azepan-2-yl]phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 2.8 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| CHEMBL4752248 | IC50 | 2.9 nM | |
| CHEMBL2347170 | IC50 | 3 nM | |
| 1-[[4-chloro-2-[(2R)-pyrrolidin-2-yl]phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 3 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 1-[(2-piperidin-3-ylphenyl)methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 3 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 2-sulfanylidene-1-[[2-[(2S,4S)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 3.4 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 1-[[4-chloro-2-[(2S)-piperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 3.6 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 2-sulfanylidene-1-[[2-[(2R,4S)-4-(trifluoromethyl)piperidin-2-yl]-3-pyridinyl]methyl]-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 3.9 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| CHEMBL2347168 | IC50 | 4 nM | |
| 7-[(2,6-dichlorophenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 4.6 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[(3R,4S,6S,10S)-4-benzyl-2-oxa-7,13,14-triazatetracyclo[14.3.1.13,6.111,14]docosa-1(19),11(21),12,16(20),17-pentaen-10-yl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 5 nM | US-10577383: Macrocyclic inhibitors of myeloperoxidase |
| CHEMBL4068067 | IC50 | 5 nM | |
| 5-(5-fluoro-1H-indol-3-yl)pentan-1-amine | IC50 | 5 nM | |
| CHEMBL4740830 | IC50 | 5 nM | |
| CHEMBL5197968 | IC50 | 5 nM | |
| 1-[[3-(1-aminocyclobutyl)phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 5 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 2-sulfanylidene-1-[[3-[(2R,4S)-4-(trifluoromethyl)piperidin-2-yl]-2-pyridinyl]methyl]-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 5.7 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| CHEMBL4782307 | IC50 | 6 nM | |
| 2-sulfanylidene-1-[[2-[(2S,4R)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 6 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| CHEMBL4453728 | IC50 | 6.7 nM | |
| 1-[2-(1-Aminoethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 7 nM | US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase |
| CHEMBL4855931 | IC50 | 7.1 nM | |
| 3-[[2-(azepan-2-yl)-4-chlorophenyl]methyl]-2-sulfanylidene-5,7,8,9-tetrahydro-4H-purin-6-one | IC50 | 7.1 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 3-[[2-(4,4-difluoropiperidin-2-yl)phenyl]methyl]-2-sulfanylidene-5,7,8,9-tetrahydro-4H-purin-6-one | IC50 | 7.2 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| US10407422, Example 130 | IC50 | 8 nM | US-10407422: Triazolopyridine inhibitors of myeloperoxidase |
| 1-{2-[(1R)-1-Aminopropyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 8.6 nM | US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase |
| CHEMBL4751166 | IC50 | 9.3 nM | |
| 1-{2-[(Cyclobutylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 10 nM | US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase |
| 7-(1-phenylethylsulfanyl)-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[[2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[[2,5-bis(trifluoromethyl)phenyl]methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[[5-fluoro-2-(trifluoromethoxy)phenyl]methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[(2-chloro-4-methylsulfonylphenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[[1-phenyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| 7-[[1-(6-pyrrolidin-1-yl-3-pyridinyl)-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | IC50 | 10 nM | US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase |
| CHEMBL2347167 | IC50 | 10 nM | |
| CHEMBL2347166 | IC50 | 10 nM | |
| 2-sulfanylidene-1-(1,2,3,4-tetrahydroisoquinolin-8-ylmethyl)-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 10 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| 1-[[2-(4-methylpiperazin-2-yl)phenyl]methyl]-2-sulfanylidene-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 10.1 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
| US10407422, Example 5 | IC50 | 11 nM | US-10407422: Triazolopyridine inhibitors of myeloperoxidase |
| CHEMBL2347176 | IC50 | 11 nM | |
| CHEMBL4862053 | IC50 | 11 nM | |
| 2-sulfanylidene-1-[[3-[(2R,4S)-4-(trifluoromethyl)piperidin-2-yl]-4-pyridinyl]methyl]-5,6,7,7a-tetrahydro-4aH-pyrrolo[3,2-d]pyrimidin-4-one | IC50 | 11.5 nM | US-20240166642: INHIBITORS OF MYELOPEROXIDASE |
ChEMBL bioactivities
936 potent at pChembl≥5 of 966 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
481 with measured affinity, of 1175 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 7-[(1R)-1-phenyl-3-[[(1S,3S)-3-phenyl-2,3-dihydro-1H-inden-1-yl]amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0010 | uM |
| 7-[(1R)-1-phenyl-3-[(4-phenyl-1-bicyclo[2.2.2]octanyl)amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1753665: Inhibition of MPO (unknown origin) chlorination activity incubated for 10 mins followed by NaCl addition by aminophenyl fluorescein assay | ic50 | 0.0010 | uM |
| 1-[[2-[(2S,4R)-4-(difluoromethyl)piperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 2144486: Inhibition of human MPO using H2O2 as substrate measured after 15 mins by chemiluminescence based assay | ic50 | 0.0010 | uM |
| 1-[[2-[amino(phenyl)methyl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0013 | uM |
| 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0015 | uM |
| 7-[(1R)-1-phenyl-3-[(4-phenylcyclohexyl)amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0020 | uM |
| 2-sulfanylidene-1-[[2-[(2R,4S)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-5H-pyrrolo[3,2-d]pyrimidin-4-one | 2144486: Inhibition of human MPO using H2O2 as substrate measured after 15 mins by chemiluminescence based assay | ic50 | 0.0020 | uM |
| 2-sulfanylidene-3-[[2-[(2S,4R)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-7H-purin-6-one | 2144486: Inhibition of human MPO using H2O2 as substrate measured after 15 mins by chemiluminescence based assay | ic50 | 0.0020 | uM |
| 1-[[2-[(2S)-piperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 2144486: Inhibition of human MPO using H2O2 as substrate measured after 15 mins by chemiluminescence based assay | ic50 | 0.0020 | uM |
| 7-[(1R)-1-phenyl-3-[[(1R,4S)-4-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl]amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0029 | uM |
| 2-sulfanylidene-3-[[2-[(2R,4R)-4-(trifluoromethyl)piperidin-2-yl]phenyl]methyl]-7H-purin-6-one | 2144486: Inhibition of human MPO using H2O2 as substrate measured after 15 mins by chemiluminescence based assay | ic50 | 0.0030 | uM |
| 1-[[2-[(2S)-4,4-difluoropiperidin-2-yl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 2144486: Inhibition of human MPO using H2O2 as substrate measured after 15 mins by chemiluminescence based assay | ic50 | 0.0030 | uM |
| 2-[2-(7-fluoro-1H-indol-3-yl)ethylsulfanyl]ethanamine | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0030 | uM |
| 3-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-7H-purin-6-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0036 | uM |
| 2-[2-(5-fluoro-1H-indol-3-yl)ethylsulfanyl]ethanamine | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0040 | uM |
| 7-[(2,6-dichlorophenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1533019: Inhibition of human PMN leukocytes MPO peroxidation activity using H2O2 as substrate preincubated for 10 mins followed by H2O2 addition and measured for 15 mins by amplex red reagent based assay | ic50 | 0.0046 | uM |
| 2-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-N-hydroxy-4-oxo-1,3-diazinane-5-carboxamide | 1802478: Myeloperoxidase Assay from Article 10.1074/jbc.M113.507756: “Potent reversible inhibition of myeloperoxidase by aromatic hydroxamates.” | ic50 | 0.0050 | uM |
| 7-[(3R,4S,6S,10S)-4-benzyl-2-oxa-7,13,14-triazatetracyclo[14.3.1.13,6.111,14]docosa-1(19),11(21),12,16(20),17-pentaen-10-yl]-2H-triazolo[4,5-b]pyridin-5-amine | 1753665: Inhibition of MPO (unknown origin) chlorination activity incubated for 10 mins followed by NaCl addition by aminophenyl fluorescein assay | ic50 | 0.0050 | uM |
| 7-[(1R)-3-[2-fluoroethyl-(4-phenyl-1-bicyclo[2.2.2]octanyl)amino]-1-phenylpropyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0050 | uM |
| 5-(5-fluoro-1H-indol-3-yl)pentan-1-amine | 1446226: Inhibition of recombinant MPO (unknown origin) assessed as reduction in taurine chloramine production preincubated with enzyme and taurine followed by H2O2 addition measured after 5 mins | ic50 | 0.0050 | uM |
| 3-(5-fluoro-1H-indol-3-yl)propyl thiocyanate | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0050 | uM |
| 2-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-N-hydroxy-6-oxo-1H-pyrimidine-5-carboxamide | 1446226: Inhibition of recombinant MPO (unknown origin) assessed as reduction in taurine chloramine production preincubated with enzyme and taurine followed by H2O2 addition measured after 5 mins | ic50 | 0.0050 | uM |
| 7-[(1R)-3-[methyl-(4-phenyl-1-bicyclo[2.2.2]octanyl)amino]-1-phenylpropyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0060 | uM |
| 4-(7-fluoro-1H-indol-3-yl)butan-1-amine | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0060 | uM |
| 7-[(2,6-dichlorophenyl)methoxy]-2H-triazolo[4,5-b]pyridin-5-amine | 1533019: Inhibition of human PMN leukocytes MPO peroxidation activity using H2O2 as substrate preincubated for 10 mins followed by H2O2 addition and measured for 15 mins by amplex red reagent based assay | ic50 | 0.0067 | uM |
| 7-[(2-fluorophenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1533018: Inhibition of human PMN leukocytes MPO chlorination activity using H2O2 as substrate preincubated for 10 mins followed by H2O2 addition and measured for 15 mins in presence of NaCl by aminophenyl fluorescein based assay | ic50 | 0.0068 | uM |
| 7-[(17S)-18-phenyl-16-oxa-2,8,9-triazapentacyclo[16.2.2.11,17.16,9.111,15]pentacosa-6(25),7,11(24),12,14-pentaen-5-yl]-2H-triazolo[4,5-b]pyridin-5-amine | 1753665: Inhibition of MPO (unknown origin) chlorination activity incubated for 10 mins followed by NaCl addition by aminophenyl fluorescein assay | ic50 | 0.0070 | uM |
| 4-(5-fluoro-1H-indol-3-yl)butan-1-amine | 1446226: Inhibition of recombinant MPO (unknown origin) assessed as reduction in taurine chloramine production preincubated with enzyme and taurine followed by H2O2 addition measured after 5 mins | ic50 | 0.0080 | uM |
| 7-(17-oxa-3,4,10-triazatetracyclo[17.3.1.13,6.112,16]pentacosa-1(23),4,6(25),12(24),13,15,19,21-octaen-7-yl)-2H-triazolo[4,5-b]pyridin-5-amine | 1753665: Inhibition of MPO (unknown origin) chlorination activity incubated for 10 mins followed by NaCl addition by aminophenyl fluorescein assay | ic50 | 0.0080 | uM |
| 7-[[5-(difluoromethyl)-2-phenyltriazol-4-yl]methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1533019: Inhibition of human PMN leukocytes MPO peroxidation activity using H2O2 as substrate preincubated for 10 mins followed by H2O2 addition and measured for 15 mins by amplex red reagent based assay | ic50 | 0.0085 | uM |
| 3-[[(2R)-oxolan-2-yl]methyl]-2-sulfanylidene-7H-purin-6-one | 1416577: Inhibition of human MPO assessed as reduction in enzyme-mediated chlorination by measuring reduction in HOCl formation preincubated for 10 mins followed by H2O2/NaCl addition and measured at 30 secs time interval for 5 mins by APF dye based fluorescence assay | ic50 | 0.0090 | uM |
| 7-[1-phenyl-3-[(1-phenyl-2-oxabicyclo[2.2.2]octan-4-yl)amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0093 | uM |
| 2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethanol | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0100 | uM |
| 2-[2-(5-fluoro-1H-indol-3-yl)ethylamino]ethanol | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0100 | uM |
| N-[3-(5-fluoro-1H-indol-3-yl)propyl]hydroxylamine | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0110 | uM |
| 7-[[5-(difluoromethyl)-2-phenyltriazol-4-yl]methoxy]-2H-triazolo[4,5-b]pyridin-5-amine | 1533019: Inhibition of human PMN leukocytes MPO peroxidation activity using H2O2 as substrate preincubated for 10 mins followed by H2O2 addition and measured for 15 mins by amplex red reagent based assay | ic50 | 0.0120 | uM |
| 1-[[4-chloro-2-[(1R)-1-(methylamino)ethyl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0127 | uM |
| N-benzyl-3-(5-fluoro-1H-indol-3-yl)propan-1-amine | 1331722: Inhibition of MPO chlorination activity (unknown origin) assessed as taurine chloramine formation after 5 mins in presence of H2O2/Cl- by HTS method | ic50 | 0.0130 | uM |
| 7-(18-oxa-3,4,10-triazatetracyclo[17.3.1.13,6.113,17]pentacosa-1(23),4,6(25),13(24),14,16,19,21-octaen-7-yl)-2H-triazolo[4,5-b]pyridin-5-amine | 1753665: Inhibition of MPO (unknown origin) chlorination activity incubated for 10 mins followed by NaCl addition by aminophenyl fluorescein assay | ic50 | 0.0140 | uM |
| N-ethyl-N-[2-(5-fluoro-1H-indol-3-yl)ethyl]methanesulfonamide | 738129: Inhibition of human recombinant MPO-mediated taurine chlorination after 5 mins by microplate assay | ic50 | 0.0140 | uM |
| 1-[[2-(aminomethyl)-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0150 | uM |
| 7-[(1R)-1-phenyl-3-[[(1R,3R)-3-phenylcyclopentyl]amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698296: Inhibition of recombinant human MPO incubated for 10 mins in presence of 120 mM NaCl by aminophenyl fluorescein based assay | ic50 | 0.0150 | uM |
| 1-[[2-(azetidin-1-ylmethyl)phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0151 | uM |
| 1-[[4-chloro-2-(methylaminomethyl)phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one | 1875005: Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay | ic50 | 0.0159 | uM |
| 7-[(3-chlorophenyl)methyl]-2H-triazolo[4,5-b]pyridin-5-amine | 1698277: Inhibition of recombinant human MPO incubated for 10 mins in presence of 240 mM NaCl and 10 uM H2O2 by aminophenyl fluorescein based assay | ic50 | 0.0160 | uM |
| methyl 3-[(5-amino-2H-triazolo[4,5-b]pyridin-7-yl)methyl]benzoate | 1698278: Inhibition of recombinant human MPO incubated for 10 mins by amplex red dye based assay | ic50 | 0.0170 | uM |
| 3-[(5-amino-2H-triazolo[4,5-b]pyridin-7-yl)methyl]benzonitrile | 1698277: Inhibition of recombinant human MPO incubated for 10 mins in presence of 240 mM NaCl and 10 uM H2O2 by aminophenyl fluorescein based assay | ic50 | 0.0170 | uM |
| 7-(18-oxa-3,4,10-triazatetracyclo[18.3.1.13,6.113,17]hexacosa-1(24),4,6(26),13(25),14,16,20,22-octaen-7-yl)-2H-triazolo[4,5-b]pyridin-5-amine | 1753665: Inhibition of MPO (unknown origin) chlorination activity incubated for 10 mins followed by NaCl addition by aminophenyl fluorescein assay | ic50 | 0.0170 | uM |
| N-[3-(5-fluoro-1H-indol-3-yl)propyl]butan-1-amine | 547368: Inhibition of recombinant MPO mediated LDL oxidation using MPO/Cl-/H2O2 system | ic50 | 0.0170 | uM |
| 4-(5-fluoro-1H-indol-3-yl)butanamide | 1446226: Inhibition of recombinant MPO (unknown origin) assessed as reduction in taurine chloramine production preincubated with enzyme and taurine followed by H2O2 addition measured after 5 mins | ic50 | 0.0180 | uM |
CTD chemical–gene interactions
201 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Hydrogen Peroxide | increases response to substance, affects activity, increases activity, increases chemical synthesis, increases degradation (+10 more) | 13 |
| Tetradecanoylphorbol Acetate | increases secretion, increases expression, increases activity, affects cotreatment, increases reaction (+2 more) | 7 |
| hydroquinone | affects cotreatment, increases metabolic processing, increases hydroxylation, affects reaction, increases cleavage (+4 more) | 5 |
| Benzene | increases metabolic processing, affects response to substance, increases response to substance | 5 |
| Hypochlorous Acid | increases chemical synthesis, increases metabolic processing, increases oxidation, increases abundance, increases reaction (+4 more) | 5 |
| Tretinoin | affects cotreatment, decreases expression, increases reaction, decreases reaction | 5 |
| Glutathione | increases glutathionylation, increases oxidation, increases activity, affects cotreatment, increases reaction (+3 more) | 4 |
| 4-aminobenzhydrazide | decreases reaction, increases chemical synthesis, increases oxidation, decreases activity, affects response to substance | 3 |
| Benzo(a)pyrene | increases methylation, increases mutagenesis, affects response to substance | 3 |
| N-Formylmethionine Leucyl-Phenylalanine | decreases reaction, increases secretion, increases activity, increases reaction | 3 |
| Sodium Azide | increases activity, increases reaction, affects cotreatment, increases oxidation, increases chemical synthesis (+1 more) | 3 |
| chlorodimedone | increases metabolic processing, increases reaction, affects binding, decreases reaction, increases abundance | 2 |
| 5,5-dimethyl-1-pyrroline-1-oxide | affects cotreatment, increases glutathionylation, increases reaction, increases activity, increases oxidation (+2 more) | 2 |
| epigallocatechin gallate | increases metabolic processing, affects cotreatment, decreases reaction, increases expression, increases chemical synthesis | 2 |
| Irinotecan | affects cotreatment, increases activity, decreases expression, increases reaction | 2 |
| Wortmannin | decreases reaction, increases chemical synthesis, increases phosphorylation, increases secretion, affects cotreatment | 2 |
| Arsenic Trioxide | affects cotreatment, decreases expression, decreases reaction | 2 |
| Carvedilol | decreases reaction, increases secretion | 2 |
| Acetylcysteine | increases reaction, increases chemical synthesis, affects binding, affects cotreatment, increases oxidation | 2 |
| Aminoglutethimide | affects cotreatment, increases oxidation, increases metabolic processing, increases expression | 2 |
| Chlorine | affects binding, increases oxidation, increases reaction, decreases activity | 2 |
| Cisplatin | decreases expression, affects response to substance | 2 |
| Indomethacin | increases activity, increases oxidation, increases response to substance, decreases reaction, increases chemical synthesis | 2 |
| Lipopolysaccharides | increases expression, decreases reaction | 2 |
| Penicillamine | increases oxidation, increases reaction, increases chemical synthesis, decreases secretion | 2 |
| Tobacco Smoke Pollution | increases response to substance, decreases expression | 2 |
| Valproic Acid | increases methylation, affects expression | 2 |
| aristolochic acid I | increases expression | 1 |
| 4-methoxybenzohydrazide | decreases reaction, increases oxidation, decreases activity | 1 |
| GSK484 | affects cotreatment, decreases reaction, increases activity | 1 |
ChEMBL screening assays
178 unique, capped per target: 165 binding, 9 functional, 4 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1027367 | Binding | Inhibition of MPO activity in TNF-alpha-stimulated human HL60 cells measured enzyme activity per 10'6 cells by spectrophotometrically | Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava. — *Bioorg Med Chem* |
| CHEMBL3636512 | ADMET | Drug metabolism assessed as formation of human MPO-mediated PTU-disulfide at 10 uM after 60 mins by LC-MS/MS analysis in presence of H2O2/Cl- | 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* |
| CHEMBL750554 | Functional | In vivo agonist efficacy as the maximal lysosomal myeloperoxidase (MPO) release in PMNL assay | Improvements in the minimum binding sequence of C5a: examination of His-67. — *J Med Chem* |
Cellosaurus cell lines
2 cell lines: 2 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B8KQ | Abcam HCT 116 MPO KO | Cancer cell line | Male |
| CVCL_B9MY | Abcam A-549 MPO KO | Cancer cell line | Male |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
showing 60 of 299 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04520308 | Phase 4 | UNKNOWN | An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis |
| NCT00009191 | Phase 4 | COMPLETED | The Depression in Alzheimer’s Disease Study (DIADS) |
| NCT00009217 | Phase 4 | COMPLETED | Treatment of Behavioral Symptoms in Alzheimer’s Disease |
| NCT00018278 | Phase 4 | COMPLETED | Electrophysiologic Measures of Treatment Response in Alzheimer Disease |
| NCT00035204 | Phase 4 | COMPLETED | A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease |
| NCT00042172 | Phase 4 | COMPLETED | Treatment for Early Memory Loss |
| NCT00046358 | Phase 4 | COMPLETED | The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease |
| NCT00104442 | Phase 4 | COMPLETED | Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease |
| NCT00120874 | Phase 4 | COMPLETED | Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training |
| NCT00142324 | Phase 4 | UNKNOWN | CALM-AD |
| NCT00165724 | Phase 4 | COMPLETED | Alzheimer’s Disease Long-term Follow-up Study (ALF Study) |
| NCT00165750 | Phase 4 | TERMINATED | Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients |
| NCT00202124 | Phase 4 | COMPLETED | Double Blind Study of Trp01 in Patients With Alzheimer’s Disease |
| NCT00208819 | Phase 4 | COMPLETED | A Comparison of Two Standard Therapies in the Management of Dementia With Agitation |
| NCT00216515 | Phase 4 | COMPLETED | The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type |
| NCT00230568 | Phase 4 | COMPLETED | EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD) |
| NCT00234637 | Phase 4 | COMPLETED | Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment |
| NCT00245206 | Phase 4 | COMPLETED | Side Effects of Newer Antipsychotics in Older Adults |
| NCT00254033 | Phase 4 | COMPLETED | Apathy Associated With Alzheimer’s Disease |
| NCT00260624 | Phase 4 | COMPLETED | Escitalopram Treatment of Patients With Agitated Dementia |
| NCT00303277 | Phase 4 | COMPLETED | Do HMG CoA Reductase Inhibitors Affect Abeta Levels? |
| NCT00305903 | Phase 4 | COMPLETED | Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease |
| NCT00306124 | Phase 4 | UNKNOWN | Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment |
| NCT00334906 | Phase 4 | COMPLETED | Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease) |
| NCT00369603 | Phase 4 | TERMINATED | Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients |
| NCT00375557 | Phase 4 | WITHDRAWN | Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients |
| NCT00381381 | Phase 4 | COMPLETED | The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease |
| NCT00385684 | Phase 4 | COMPLETED | Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT) |
| NCT00401167 | Phase 4 | COMPLETED | Memantine for Agitation and Aggression in Severe Alzheimer’s Disease |
| NCT00403520 | Phase 4 | COMPLETED | Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers |
| NCT00417482 | Phase 4 | COMPLETED | Antipsychotic Discontinuation in Alzheimer’s Disease |
| NCT00443014 | Phase 4 | COMPLETED | The Dementia Study in Northern Norway |
| NCT00469456 | Phase 4 | COMPLETED | Effect of Memantine on Functional Communication in Patients With Alzheimer’s Disease |
| NCT00476008 | Phase 4 | COMPLETED | Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer’s Disease |
| NCT00477659 | Phase 4 | COMPLETED | Neural Correlates In Mild Alzheimer’s Disease |
| NCT00480870 | Phase 4 | COMPLETED | The Effect of Anticholinesterase Drugs on Sleep in Alzheimer’s Disease Patients |
| NCT00495820 | Phase 4 | COMPLETED | Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study |
| NCT00523666 | Phase 4 | UNKNOWN | Diffusion Tensor Weighted MRI in Alzheimer’s Disease Modifying Treatment Effects of Galantamine (Reminyl®) |
| NCT00549601 | Phase 4 | COMPLETED | Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer’s Disease |
| NCT00551161 | Phase 4 | COMPLETED | Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer’s Disease |
| NCT00561392 | Phase 4 | COMPLETED | Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer’s Disease |
| NCT00622713 | Phase 4 | COMPLETED | A 24 Week, Multicenter, Open, Evaluation of the Clinical Effectiveness of the Once-daily 10 cm^2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer’s Disease (EXTRA) |
| NCT00626210 | Phase 4 | TERMINATED | Modafinil Treatment for Sleep/Wake Disturbances in Older Adults |
| NCT00626613 | Phase 4 | UNKNOWN | The Relationship Between Risperdal Treatment and Quality of Life in Patients With Alzheimer’s Disease and Behavioural and Psychological Symptoms of Dementia (BPSD) |
| NCT00649220 | Phase 4 | TERMINATED | Memantine and Antipsychotics Use |
| NCT00706186 | Phase 4 | TERMINATED | Safety and Feasibility of Sodium Oxybate in Mild Alzheimer’s Disease Patients |
| NCT00711204 | Phase 4 | WITHDRAWN | Evaluating The Impact Of Donepezil Hydrochloride (Aricept) On Behavioral And Psychological Symptoms In Patients With Severe Alzheimer’s Disease |
| NCT00731224 | Phase 4 | COMPLETED | Compliance and Tolerability of Rivastigmine Transdermal Patch 10 cm² in Patients With Probable Alzheimer’s Disease. |
| NCT00792662 | Phase 4 | WITHDRAWN | Improving Function, Quality of Life, Glycemia in Diabetics With Dementia |
| NCT00800709 | Phase 4 | COMPLETED | Memantine and Changes of Biological Markers and Brain PET Imaging in Alzheimer’s Disease |
| NCT00862940 | Phase 4 | COMPLETED | A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer’s Disease |
| NCT00933608 | Phase 4 | COMPLETED | Effects of Memantine on Magnetic Resonance (MR) Spectroscopy in Subjects at Risk for Alzheimer’s Disease |
| NCT00948766 | Phase 4 | COMPLETED | Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer’s Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44 |
| NCT00950430 | Phase 4 | ENROLLING_BY_INVITATION | Imaging of Brain Amyloid Plaques in the Aging Population |
| NCT00980785 | Phase 4 | COMPLETED | Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer’s |
| NCT01025466 | Phase 4 | COMPLETED | Exelon Patch and Combination With Memantine Comparative Trial |
| NCT01047579 | Phase 4 | COMPLETED | A 12 Week, Multicenter, Open Label Evaluation of Caregiver Preference, Safety and Tolerability of Exelon® Patch (Rivastigmine Transdermal) in Patients With Alzheimer’s Disease |
| NCT01054976 | Phase 4 | COMPLETED | The Efficacy of Galantamine Treatment on Attention in Patients With Alzheimer’s Disease |
| NCT01119638 | Phase 4 | COMPLETED | Escitalopram Treatment for BPSD in Alzheimer’s Disease in Comparison to Risperidone |
| NCT01122329 | Phase 4 | COMPLETED | A Positron Emission Tomography (PET) Study Evaluating Brain Metabolism of a Medical Food in Alzheimer’s Disease |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for MPO across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Associated diseases: myeloperoxidase deficiency
- Targeted by drugs: Verdiperstat
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Alzheimer disease type 1, myeloperoxidase deficiency