LPO

Summary

LPO (lactoperoxidase, HGNC:6678) is a protein-coding gene on chromosome 17q22, encoding Lactoperoxidase (P22079). Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2).

This gene encodes a member of the peroxidase family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Following its secretion from salivary, mammary, and other mucosal glands, this enzyme catalyzes the generation of the antimicrobial substance hypothiocyanous acid. This gene is present in a gene cluster on chromosome 17. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed.

Source: NCBI Gene 4025 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 125 total — 1 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6678
Approved symbol	LPO
Name	lactoperoxidase
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	SPO
Ensembl gene	ENSG00000167419
Ensembl biotype	protein_coding
OMIM	150205
Entrez	4025

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000262290, ENST00000389576, ENST00000421678, ENST00000543544, ENST00000578403, ENST00000578643, ENST00000580346, ENST00000580890, ENST00000581008, ENST00000582328, ENST00000582684, ENST00000866990

RefSeq mRNA: 2 — MANE Select: NM_006151 NM_001160102, NM_006151

CCDS: CCDS32689, CCDS54149

Canonical transcript exons

ENST00000262290 — 13 exons

Exon	Start	End
ENSE00002204284	58252182	58252506
ENSE00002227590	58250415	58250621
ENSE00003525065	58249566	58249695
ENSE00003533774	58267787	58268518
ENSE00003555595	58267349	58267586
ENSE00003584486	58254811	58254971
ENSE00003589986	58249060	58249177
ENSE00003597948	58243994	58244081
ENSE00003607267	58266153	58266326
ENSE00003636259	58242978	58243055
ENSE00003666965	58247478	58247638
ENSE00003678442	58264722	58264974
ENSE00003889096	58238584	58238739

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 99.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.7884 / max 3878.4082, expressed in 50 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161902	2.5260	15
161900	2.5084	38
161898	0.5710	18
161901	0.1562	7
161899	0.0267	5

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.61	gold quality
trachea	UBERON:0003126	97.49	gold quality
saliva-secreting gland	UBERON:0001044	87.16	gold quality
minor salivary gland	UBERON:0001830	83.82	gold quality
mouth mucosa	UBERON:0003729	79.68	gold quality
nasal cavity mucosa	UBERON:0001826	79.39	gold quality
Brodmann (1909) area 10	UBERON:0013541	70.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.00	gold quality
bone marrow cell	CL:0002092	65.19	silver quality
endometrium epithelium	UBERON:0004811	64.72	gold quality
frontal pole	UBERON:0002795	64.43	gold quality
middle frontal gyrus	UBERON:0002702	64.24	gold quality
paraflocculus	UBERON:0005351	64.10	gold quality
bone marrow	UBERON:0002371	63.08	gold quality
diaphragm	UBERON:0001103	61.61	gold quality
gingiva	UBERON:0001828	61.36	silver quality
pharyngeal mucosa	UBERON:0000355	61.35	silver quality
substantia nigra	UBERON:0002038	60.09	gold quality
substantia nigra pars reticulata	UBERON:0001966	60.07	gold quality
superior surface of tongue	UBERON:0007371	60.02	gold quality
sperm	CL:0000019	59.96	gold quality
pancreatic ductal cell	CL:0002079	59.89	silver quality
male germ cell	CL:0000015	59.36	gold quality
midbrain	UBERON:0001891	58.17	gold quality
tongue	UBERON:0001723	57.60	silver quality
tonsil	UBERON:0002372	57.17	gold quality
stromal cell of endometrium	CL:0002255	57.08	gold quality
vena cava	UBERON:0004087	56.31	gold quality
gingival epithelium	UBERON:0001949	56.24	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	13.00
E-ANND-3	yes	6.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting LPO, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-4800-5P	97.22	65.91	324
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-6874-5P	95.73	64.94	545
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 9)

• a functional LPO system exists in human airways and may contribute to airway host defense against infection (PMID:12626341)
• lactoperoxidase may play an important role in the metabolic events associated with Parkinson’s disease (PMID:15384204)
• Analysis of the role of thiocyanate (SCN-), in modulating the catalytic activity of myeloperoxidase (MPO) and other members of the lactoperoxidase (LPO) and eosinophil peroxidase (EPO) (PMID:15894800)
• Splice variants may contribute to LPO molecular heterogeneity and its regulation by intracellular compartmental localization in respiratory epithelium. (PMID:19059195)
• Oral peroxidase activity as a marker of chronic alcohol abuse may help in the diagnosis of alcoholism. (PMID:23042278)
• establish urate as a likely physiological substrate for LPO that will influence host defense and give rise to reactive electrophilic metabolites (PMID:24928513)
• High intensity of caries is associated with increased levels of some salivary components - sIgA, histatin-5 and lactoperoxidase. (PMID:24974109)
• LPO mRNA was undetectable in the gastric mucosa. (PMID:27048452)
• The crystal structure of the complex of LPO with MZY showed that MZY bound to LPO in the substrate-binding site on the distal heme side. MZY was oriented in the substrate-binding site in such a way that the sulfur atom is at a distance of 2.58 A from the heme iron (PMID:28653416)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	epx	ENSDARG00000012535
mus_musculus	Lpo	ENSMUSG00000009356
rattus_norvegicus	Lpo	ENSRNOG00000008422
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): MPO (ENSG00000005381), TPO (ENSG00000115705), EPX (ENSG00000121053), PXDN (ENSG00000130508), PXDNL (ENSG00000147485)

Protein

Protein identifiers

Lactoperoxidase — P22079 (reviewed: P22079)

Alternative names: Salivary peroxidase

All UniProt accessions (5): P22079, F5H386, H0Y3I2, J3KT11, J3QSD8

UniProt curated annotations — full annotation on UniProt →

Function. Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2). Also involved in the conversion of iodide (I(-)) into hypoiodite (IO(-)) in the presence of H2O2. Responsible for the inactivation of a wide range of micro-organisms and hence, important component of defense mechanism. Shows antibacterial properties against Pseudomonas aeruginosa. The lactoperoxidase-SCN(-)-H2O2 system shows antibacterial properties against Burkholderia cepacia and Haemophilus influenzae in vitro. Present in mammary and salivary gland secretions and may contribute to airway host defense against infection. May contribute to maintaining an appropriate H2O2 cellular level, therefore protecting cells from H2O2-caused injuries and inflammation.

Subcellular location. Secreted. Cytoplasm.

Tissue specificity. Mammary gland, milk and salivary gland. Found in bronchial submucosal glands.

Cofactor. Binds 1 Ca(2+) ion per heterodimer. Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.

Miscellaneous. Thiocyanate (SCN(-)) and hypothiocyanite (OSCN(-)) are bound in the distal heme cavity. The iodide ion (I(-)) occupies a position which is stabilized by the interactions with heme moiety, His-226, Arg-372 and Glu-375. Hydrogen peroxide is held between the heme iron and His-226.

Similarity. Belongs to the peroxidase family. XPO subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P22079-1	1	yes
P22079-2	2, V3

RefSeq proteins (2): NP_001153574, NP_006142* (*=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

Catalyzed reactions (Rhea), 3 shown:

• 2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2 H2O (RHEA:56136)
• thiocyanate + H2O2 + H(+) = hypothiocyanous acid + H2O (RHEA:69416)
• iodide + H2O2 = hypoiodite + H2O (RHEA:69420)

UniProt features (35 total): binding site 8, sequence variant 7, disulfide bond 6, glycosylation site 4, modified residue 2, sequence conflict 2, signal peptide 1, propeptide 1, site 1, chain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22079-F1	92.43	0.80

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 (2): 372 (transition state stabilizer); 226 (proton acceptor)

Ligand- & substrate-binding residues (8): 375 (covalent); 468 (axial binding residue); 225 (covalent); 227; 301; 303; 305; 307

Post-translational modifications (2): 315, 482

Disulfide bonds (6): 132–145, 246–256, 250–274, 354–365, 573–630, 671–696

Glycosylation sites (4): 106, 212, 322, 358

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8941413	Events associated with phagocytolytic activity of PMN cells

MSigDB gene sets: 82 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, CEBPB_01, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE, GOBP_SENSORY_PERCEPTION_OF_TASTE, WTGAAAT_UNKNOWN, GOBP_DETOXIFICATION, GGGNNTTTCC_NFKB_Q6_01, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOMF_ANTIOXIDANT_ACTIVITY

GO Biological Process (6): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), response to oxidative stress (GO:0006979), defense response to bacterium (GO:0042742), hydrogen peroxide catabolic process (GO:0042744), thiocyanate metabolic process (GO:0018969), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (6): heme binding (GO:0020037), thiocyanate peroxidase activity (GO:0036393), metal ion binding (GO:0046872), lactoperoxidase activity (GO:0140825), peroxidase activity (GO:0004601), oxidoreductase activity (GO:0016491)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), basolateral plasma membrane (GO:0016323), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ROS and RNS production in phagocytes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peroxidase activity	2
cellular anatomical structure	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
response to stress	1
defense response	1
response to bacterium	1
catabolic process	1
hydrogen peroxide metabolic process	1
sulfur compound metabolic process	1
cellular detoxification	1
tetrapyrrole binding	1
thiocyanate metabolic process	1
cation binding	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
catalytic activity	1
intracellular anatomical structure	1
basal plasma membrane	1
plasma membrane region	1
extracellular vesicle	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPO	LALBA	P00709	952
LPO	LTF	P02788	945
LPO	ALB	P02768	690
LPO	CSN3	P07498	569
LPO	DUOX1	Q9NRD9	521
LPO	STATH	P02808	511
LPO	PIP	P12273	497
LPO	CSN2	P05814	491
LPO	CSN1S1	P47710	488
LPO	PIGR	P01833	478
LPO	HTN3	P15516	477
LPO	HTN1	P15515	431
LPO	CD44	P16070	420
LPO	CST4	P01036	419
LPO	CTRB2	Q6GPI1	413

IntAct

7 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
PLXNA4	CRYZL1	psi-mi:“MI:0914”(association)	0.560
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): LPO (Affinity Capture-MS), LPO (Affinity Capture-MS), LPO (Proximity Label-MS), LPO (Affinity Capture-MS), LPO (Affinity Capture-MS), LPO (Affinity Capture-RNA), LPO (Co-fractionation), LPO (Affinity Capture-MS)

ESM2 similar proteins: A0A1Y9G8H0, A0A452E9Y6, A5JUY8, A8WQH2, B3A0Q8, F9FAJ9, G4N2X9, G4N4J5, G5EG78, H2A0M7, O02768, O19183, O61213, O62664, O62698, O62725, O97554, P05979, P07202, P09933, P14650, P22079, P22437, P23219, P27607, P29812, P35354, P35355, P35419, P70682, P79208, P80025, P82600, P90820, Q01603, Q05769, Q1ENI8, Q20616, Q23490, Q4WY82

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A4IGL7, A5JUY8, B3A0P3, B3A0Q8, G5EG78, H2A0M7, O61213, P09933, P11247, P11678, P22079, P80025, P82600, P90820, Q01603, Q20616, Q23490, Q3UQ28, Q5SW46, Q6TMK4, Q7QH73, Q8CIY2, Q8HYB7, Q8R481, Q92626, Q9ES45, Q9VEG6, Q9VZZ4, A8WQH2, O02768, P05164, P07202, P14650, P35355, P35419, P49290, Q1ENI8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

125 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	106
Likely benign	4
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1710927	GRCh37/hg19 17q22(chr17:55043662-56728123)x1	Pathogenic

SpliceAI

2835 predictions. Top by Δscore:

Variant	Effect	Δscore
17:58218618:A:AC	donor_gain	1.0000
17:58218619:C:CC	donor_gain	1.0000
17:58219197:C:A	donor_gain	1.0000
17:58250410:TGTA:T	acceptor_loss	1.0000
17:58250411:GTA:G	acceptor_loss	1.0000
17:58250413:A:AG	acceptor_gain	1.0000
17:58250414:G:GG	acceptor_gain	1.0000
17:58250551:G:GT	donor_gain	1.0000
17:58250551:G:T	donor_gain	1.0000
17:58250585:G:GG	donor_gain	1.0000
17:58250636:C:G	donor_gain	1.0000
17:58252180:A:AG	acceptor_gain	1.0000
17:58252181:G:GA	acceptor_gain	1.0000
17:58252181:GTTCC:G	acceptor_gain	1.0000
17:58264990:G:T	donor_gain	1.0000
17:58266147:T:A	acceptor_gain	1.0000
17:58266148:G:A	acceptor_gain	1.0000
17:58266148:GGCA:G	acceptor_loss	1.0000
17:58266151:A:AG	acceptor_gain	1.0000
17:58266151:A:T	acceptor_loss	1.0000
17:58266151:AGGT:A	acceptor_gain	1.0000
17:58266152:G:GA	acceptor_loss	1.0000
17:58266152:G:GG	acceptor_gain	1.0000
17:58266152:GGT:G	acceptor_gain	1.0000
17:58266152:GGTG:G	acceptor_gain	1.0000
17:58266322:ACCTG:A	donor_gain	1.0000
17:58266323:CCTG:C	donor_gain	1.0000
17:58266323:CCTGG:C	donor_loss	1.0000
17:58266324:CTG:C	donor_gain	1.0000
17:58266325:TG:T	donor_gain	1.0000

AlphaMissense

4655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:58250499:T:A	W220R	0.988
17:58250499:T:C	W220R	0.988
17:58266303:G:C	R557P	0.988
17:58266309:G:C	R559P	0.987
17:58254868:G:C	R388P	0.986
17:58254880:G:C	R392P	0.985
17:58252461:T:A	C354S	0.981
17:58252462:G:C	C354S	0.981
17:58267574:G:C	R640P	0.979
17:58252494:T:A	C365S	0.977
17:58252494:T:C	C365R	0.977
17:58252495:G:C	C365S	0.977
17:58264958:G:C	W501C	0.977
17:58264958:G:T	W501C	0.977
17:58266295:C:A	N554K	0.977
17:58266295:C:G	N554K	0.977
17:58266317:G:T	G562W	0.977
17:58267360:T:A	W569R	0.976
17:58267360:T:C	W569R	0.976
17:58254867:C:A	R388S	0.975
17:58254895:T:C	L397P	0.975
17:58250428:C:T	S196F	0.974
17:58252496:C:G	C365W	0.974
17:58252462:G:A	C354Y	0.973
17:58254946:G:C	R414P	0.973
17:58267866:T:A	C671S	0.973
17:58267867:G:C	C671S	0.973
17:58249624:T:C	Y168H	0.972
17:58249625:A:G	Y168C	0.972
17:58252461:T:C	C354R	0.972

dbSNP variants (sampled 300 via entrez): RS1000156234 (17:58238663 G>C), RS1000159089 (17:58268652 A>G), RS1000306544 (17:58254412 T>C), RS1000358578 (17:58254120 T>TAGAA), RS1000409772 (17:58262371 C>A,T), RS1000462036 (17:58268937 T>A), RS1000549128 (17:58255748 C>T), RS1000687463 (17:58243251 C>T), RS1000835926 (17:58236941 A>G), RS1000844728 (17:58243382 G>A), RS1000895563 (17:58243659 C>A), RS1000988262 (17:58243559 A>G), RS1001332555 (17:58239161 T>C), RS1001373141 (17:58249265 G>A), RS1001509293 (17:58240816 T>C)

Disease associations

OMIM: gene MIM:150205 | disease phenotypes: MIM:254600, MIM:104300

GenCC curated gene-disease

Mondo (2): myeloperoxidase deficiency (MONDO:0009694), Alzheimer disease type 1 (MONDO:0007088)

Orphanet (1): Myeloperoxidase deficiency (Orphanet:2587)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003263_70	Post bronchodilator FEV1 in COPD	4.000000e-06
GCST003265_272	Post bronchodilator FEV1/FVC ratio in COPD	2.000000e-06
GCST003265_275	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_303	Post bronchodilator FEV1/FVC ratio in COPD	2.000000e-06
GCST004618_42	White blood cell count (basophil)	1.000000e-10
GCST006585_923	Blood protein levels	8.000000e-25
GCST90002379_183	Basophil count	4.000000e-28
GCST90002380_2	Basophil percentage of white cells	4.000000e-18
GCST90002394_405	Monocyte percentage of white cells	3.000000e-19

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536594	Alzheimer disease type 1 (supp.)
C562864	Myeloperoxidase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5898 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,518 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1515	METHIMAZOLE	4	18,943
CHEMBL1518	PROPYLTHIOURACIL	4	15,046
CHEMBL508102	CARBIMAZOLE	4	3,772
CHEMBL1330588	METHYLTHIOURACIL	2	1,757

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

8 potent at pChembl≥5 of 19 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.29	IC50	510	nM	METHIMAZOLE
6.23	IC50	590	nM	CHEMBL5517779
5.83	IC50	1490	nM	METHYLTHIOURACIL
5.66	IC50	2200	nM	CHEMBL5555319
5.26	IC50	5500	nM	CHEMBL5560226
5.14	IC50	7300	nM	CHEMBL5557885
5.12	IC50	7520	nM	PROPYLTHIOURACIL
5.00	IC50	1.01e+04	nM	CHEMBL457523

PubChem BioAssay actives

7 with measured affinity, of 32 total; 7 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
Methimazole	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	0.5100	uM
1,3-dimethylimidazole-2-selone	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	0.5900	uM
6-methyl-2-sulfanylidene-1H-pyrimidin-4-one	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	1.4900	uM
1-[(3-methoxyphenyl)methyl]-3-methylimidazole-2-selone	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	2.2000	uM
1,3-bis[(3-methoxyphenyl)methyl]imidazole-2-selone	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	5.5000	uM
9989524	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	7.3000	uM
Propylthiouracil	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	7.5200	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
Estradiol	affects cotreatment, decreases expression, affects expression	2
Paraquat	decreases reaction, increases expression	2
Valproic Acid	decreases methylation, decreases expression	2
naringenin	increases expression, decreases reaction	1
fenvalerate	decreases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
cerous chloride	affects cotreatment, increases expression	1
lanthanum chloride	affects cotreatment, increases expression	1
benzidine	increases metabolic processing	1
coumarin	decreases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
fumonisin B1	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
bisphenol AF	decreases expression	1
Gabapentin	decreases expression	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Cisplatin	decreases expression	1
Colchicine	decreases expression	1
Diethylstilbestrol	decreases expression	1
Endosulfan	decreases expression	1
Fluorouracil	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases metabolic processing	1
Hydroxyurea	decreases expression	1
Lipopolysaccharides	increases expression, decreases expression, affects response to substance	1
Medroxyprogesterone	affects cotreatment, affects expression	1
Nitrites	affects cotreatment, increases metabolic processing	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4263009	Binding	Inhibition of recombinant human LPO isoform-1 (26 to 712 residues) expressed in baculovirus infected insect cells assessed as reduction in H2O2-catalyzed 3,5-iodo tyrosine formation using 3-iodotyrosine and potassium iodide preincubated for	Triazolopyrimidines identified as reversible myeloperoxidase inhibitors. — Medchemcomm

Clinical trials (associated diseases)

21 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04520308	PHASE4	UNKNOWN	An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis
NCT02380573	PHASE2	COMPLETED	Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer’s Disease
NCT03806478	PHASE2	UNKNOWN	Study of APH-1105 in Patients With Mild to Moderate Alzheimer’s Disease
NCT07011706	PHASE2	ACTIVE_NOT_RECRUITING	ATI-045 Versus Placebo in Patients With Moderate-to-Severe Atopic Dermatitis
NCT07252440	PHASE2	RECRUITING	A Study to Evaluate the Efficacy and Safety of TTYP01 Tablets in Early Symptomatic Alzheimer’s Disease
NCT03932916	PHASE1	COMPLETED	Safety and Pharmacokinetic of Donepezil Pamoate in Healthy Subjects
NCT06593626	PHASE1	COMPLETED	A Phase I Clinical Study on the Safety and Pharmacokinetics of [18F]Florbetazine Injection
NCT05984784	PHASE1/PHASE2	TERMINATED	A Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of IMG-007 in Adults With Atopic Dermatitis (AD)
NCT01733355	EARLY_PHASE1	TERMINATED	A Phase 0, Open Label, Multi-center Exploratory and Safety Study of [F-18]T807
NCT05469009	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer’s Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
NCT01190904	Not specified	COMPLETED	Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes
NCT02273895	Not specified	COMPLETED	The Use of EEG in Alzheimer’s Disease, With and Without Scopolamine - A Pilot Study
NCT04100889	Not specified	WITHDRAWN	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Alzheimer’s Disease
NCT05078944	Not specified	COMPLETED	Progress of Mild Alzheimer’s Disease in Participants on Acupuncture Versus Sham Acupuncture
NCT05372458	Not specified	UNKNOWN	The Mechanism Study of Diabetic Pancreatic Amyloid Deposition on Cognitive Dysfunction in Alzheimer’s Disease
NCT05637801	Not specified	ACTIVE_NOT_RECRUITING	A Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (HOPE Study)
NCT06039267	Not specified	COMPLETED	Brain Health & the Microbiome
NCT06155201	Not specified	UNKNOWN	Development and Application of Intelligent Diagnosis and Treatment Norms for Children and Adolescents With Mental Disorders
NCT06245031	Not specified	ENROLLING_BY_INVITATION	Extension to a Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (OLE Hope Study, CA-0015)
NCT06335836	Not specified	RECRUITING	The Effects of Social Isolation and Social Interaction on the Risk of Dementia Progression and Brain Function in SCD (Subjective Cognitive Decline, SCD)
NCT07100470	Not specified	NOT_YET_RECRUITING	Metabolic Characterization of Alzheimer’s Disease and Frontotemporal Dementia by 23Na-MRI and FDG-PET