MMP8

Summary

MMP8 (matrix metallopeptidase 8, HGNC:7175) is a protein-coding gene on chromosome 11q22.2, encoding Neutrophil collagenase (P22894). Can degrade fibrillar type I, II, and III collagens.

This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4317 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 84 total — 1 pathogenic
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7175
Approved symbol	MMP8
Name	matrix metallopeptidase 8
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000118113
Ensembl biotype	protein_coding
OMIM	120355
Entrez	4317

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 nonsense_mediated_decay, 2 protein_coding

ENST00000236826, ENST00000438475, ENST00000528662, ENST00000531168, ENST00000532799, ENST00000533258

RefSeq mRNA: 3 — MANE Select: NM_002424 NM_001304441, NM_001304442, NM_002424

CCDS: CCDS8320

Canonical transcript exons

ENST00000236826 — 10 exons

Exon	Start	End
ENSE00001322445	102711796	102713457
ENSE00002691337	102724754	102724954
ENSE00003464128	102713754	102713857
ENSE00003481417	102721614	102721762
ENSE00003483799	102714556	102714709
ENSE00003502319	102722429	102722673
ENSE00003510095	102715304	102715437
ENSE00003629849	102718414	102718575
ENSE00003637733	102721401	102721526
ENSE00003688478	102716302	102716419

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 98.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.5258 / max 1792.8899, expressed in 130 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121984	2.5258	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	98.55	gold quality
bone marrow	UBERON:0002371	98.49	gold quality
bone marrow cell	CL:0002092	98.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.18	silver quality
monocyte	CL:0000576	78.89	gold quality
mononuclear cell	CL:0000842	78.58	gold quality
leukocyte	CL:0000738	77.47	gold quality
blood	UBERON:0000178	75.86	gold quality
amniotic fluid	UBERON:0000173	75.61	gold quality
spleen	UBERON:0002106	74.00	gold quality
granulocyte	CL:0000094	66.06	gold quality
upper lobe of left lung	UBERON:0008952	61.87	gold quality
upper lobe of lung	UBERON:0008948	61.65	gold quality
right lung	UBERON:0002167	60.69	gold quality
lower lobe of lung	UBERON:0008949	59.00	silver quality
tibialis anterior	UBERON:0001385	56.92	silver quality
pancreatic ductal cell	CL:0002079	56.24	silver quality
lung	UBERON:0002048	56.03	gold quality
deltoid	UBERON:0001476	55.24	gold quality
buccal mucosa cell	CL:0002336	54.81	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
epithelial cell of pancreas	CL:0000083	51.98	gold quality
quadriceps femoris	UBERON:0001377	51.90	gold quality
myocardium	UBERON:0002349	51.72	gold quality
left ventricle myocardium	UBERON:0006566	51.17	gold quality
cardiac muscle of right atrium	UBERON:0003379	51.07	gold quality
vastus lateralis	UBERON:0001379	50.66	gold quality
upper arm skin	UBERON:0004263	50.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.44	gold quality
frontal pole	UBERON:0002795	50.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.04

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IL10	Repression
IL6	Activation
NOS2	Activation

Upstream regulators (CollecTRI, top): CEBPA, CEBPE, GFI1

miRNA regulators (miRDB)

80 targeting MMP8, 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-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-892A	99.54	68.16	1141

Literature-anchored findings (GeneRIF, showing 40)

• expression in normal and malignant melanocytic cells (PMID:11731274)
• MMP-8 cleaves TFPI following Ser(174) within the connecting region between the second and third Kunitz domains (PMID:12117418)
• gelatinase B and neutrophil collagenase cleave MIG and IP-10 (PMID:14550288)
• Matrix metalloproteinase-8 is produced primarily by chorionic cells in human fetal membranes, and the level of matrix metalloproteinase-8 protein and messenger RNA expression in fetal membranes increases during labor. (PMID:15042023)
• membrane-bound MMP-8 on PMN cleaves types I and II collagens, and alpha(1)-proteinase inhibitor, but is substantially resistant to inhibition by tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. (PMID:15187163)
• Functionally significant single nucleotide polymorphisms of the MMP8 promoter haplotypes and preterm premature rupture of membranes were evaluated. (PMID:15367487)
• in the later stages of myeloid development, MMP8 and other SGP genes are coordinately upregulated, and members of the C/EBP family, in particular C/EBPalpha and C/EBPepsilon, play specific and unique roles in upregulating their expression (PMID:15661397)
• Significantly elevated metalloproteinase 8 in broncho-alveolar lavage fluid is associated with Bronchiolitis obliterans (PMID:15888067)
• significantly elevated sinus mucus levels associated with elevated IL-8 levels in chronic rhinosinusitis with nasal polyposis (CRSwNP); IL-8 and MMP-8 seemingly form an inductive cytokine-proteinase cascade in CRSwNP pathogenesis (PMID:16134994)
• x-ray crystallographic analysis reveals that in a complex with MMP-8, N-hydroxyurea binds the catalytic zinc ion in a monodentate rather than bidentate mode and with high out-of-plane distortion of the amide bonds (PMID:16242329)
• MMP-8 has a role in carotid plaque progression (PMID:16259988)
• A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and abdominal aortic aneurysm rupture. (PMID:16432074)
• findings show that bacterial vaginosis is associated with increased levels of matrix metalloproteinase-8(MMP-8) in vaginal fluid (PMID:16872847)
• The expression of matrix-modeling genes in chronic idiopathic myelofibrosis (cIMF) is not influenced by the JAK2 mutation status but is predominantly related to the stage of disease. (PMID:16877349)
• Immunofluorescence intensity, representing MMP-8 expression, in the periodontal tissues of smokers (30 fields from 6 subjects, mean 1154+/-124 units) was significantly higher than that in the periodontal tissues of non-smokers. (PMID:16928431)
• distinct deficits in NO production and elevations in MMP-8 and -9 expression in diabetic human skin fibroblasts compared to normal (PMID:17418871)
• C-terminus of ephrin-B1 regulates activation of the extracellular release of MMP-8 without requirement of de novo protein synthesis. (PMID:17567680)
• Data show that serum MMP-8 concentration is closely associated with ACS, particularly AMI, and may serve as an indicator for predicting ACS and AMI. (PMID:17584650)
• Results show that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans. (PMID:17728507)
• Serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and associate with the worst cardiovascular outcome. (PMID:17932311)
• MMP8 gene variation may influence breast cancer prognosis and support the notion that MMP8 has an inhibitory effect on cancer metastasis. (PMID:17974962)
• In an in vitro atherosclerosis model neutrophil infiltration was mediated via IL-8-signalling and accompanied by release of MMP-8 and induction of endothelial cell apoptosis. (PMID:18278188)
• MMP8, but not MMP1 or MMP13, may affect the metastatic behaviour of breast cancer cells through protection against lymph node metastasis (PMID:18366705)
• Total MMP-8 immunoreactivity, the proportion of active MMP-9, and gelatinolytic activity in urine were significantly higher in diabetic nephropathy patients than in controls (PMID:18428024)
• high serum MMP-8 levels in melanoma patients were significantly related to presence of vascular invasion (P=0.001) in primary tumour, tumour ulceration (P=0.003) and tumour bleeding (P=0.033) (PMID:18626311)
• In patients with high-risk bacteria, MMP-8-, MMP-9- and TIMP-1-concentrations were higher than in patients with low-risk bacteria. (PMID:18700005)
• Functional polymorphisms in the promoter of MMP-8 do not significantly confer susceptibility to hepatocellular carcinoma in a southern Chinese population. (PMID:18768525)
• Non-surgical periodontal treatment was effective in reducing the levels of MMP8 in gingival crevicular fluid from diabetic patients with chronic periodontitis. (PMID:18980523)
• a C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer, but does not seem to modify or be an independent prognostic factor for overall survival (PMID:19094243)
• MMP-8 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. (PMID:19159011)
• Expression of wild-type but not mutant MMP8 in human melanoma cells inhibited growth on soft agar in vitro and tumor formation in vivo, suggesting that wild-type MMP-8 has the ability to inhibit melanoma progression. (PMID:19330028)
• Obese children and adolescents had higher circulating MMP-8 concentrations, lower plasma TIMP-1 concentrations, and higher MMP-8/TIMP-1 ratios than non obese controls. (PMID:19358835)
• Primary cultures stromal cells from giant cell tumour of bone produce MMP-1 and MMP-13 but not MMP-8.. (PMID:19442604)
• Patients with coronary heart disease showed increased levels of MMP2 and MMP9. (PMID:19460733)
• plasma MMP-8 levels were found to be high in patients with unstable angina (UAP), suggesting that MMP-8 levels in UAP may reflect coronary plaque instability and that MMP-8 is a promising biomarker for UAP. (PMID:19674746)
• Reverse transcriptase (RT)-PCR analysis revealed that Prevotella intermedia ATCC 25611 supernatant increased MMP-1 and MMP-8 mRNA expression in a concentration- and time-dependent manner. (PMID:19708869)
• Results indicate that MMP8 is an important player in atherosclerosis. (PMID:19745165)
• increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy (PMID:19751716)
• Pneumolysin induces release of matrix metalloproteinase-8 and -9 from human neutrophils (PMID:19880617)
• Higher levels of MMP-8 were found in the gingival crevicular fluid of chronic periodontitis patients compared with controls, and these markers decreased 3 months after periodontal therapy. (PMID:19995403)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mmp8	ENSMUSG00000005800
rattus_norvegicus	Mmp8	ENSRNOG00000009907
drosophila_melanogaster	Mmp1	FBGN0035049
caenorhabditis_elegans		WBGENE00006987
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00020646
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Neutrophil collagenase — P22894 (reviewed: P22894)

Alternative names: Matrix metalloproteinase-8, PMNL collagenase

All UniProt accessions (5): P22894, E9PIY7, E9PJB3, E9PL87, H7C1M3

UniProt curated annotations — full annotation on UniProt →

Function. Can degrade fibrillar type I, II, and III collagens.

Subcellular location. Cytoplasmic granule. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Neutrophils.

Activity regulation. Cannot be activated without removal of the activation peptide.

Cofactor. Binds 3 Ca(2+) ions per subunit. Binds 2 Zn(2+) ions per subunit.

Domain organisation. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (3): NP_001291370, NP_001291371, NP_002415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR002477	Peptidoglycan-bd-like	Domain
IPR006026	Peptidase_Metallo	Domain
IPR018486	Hemopexin_CS	Conserved_site
IPR018487	Hemopexin-like_repeat	Repeat
IPR021158	Pept_M10A_Zn_BS	Binding_site
IPR021190	Pept_M10A	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471

Enzyme classification (BRENDA):

• EC 3.4.24.34 — neutrophil collagenase (BRENDA: 3 organisms, 57 substrates, 73 inhibitors, 21 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BOVINE COLLAGEN I	0.0002–14.4	6
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-CYCLOHEXYLALA	0.0279–0.0622	4
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LEU-GLY-LEU-L	0.0194–0.0465	3
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LEU-GLY-LEU-D	0.0265–0.046	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LEU-GLY-LEU-D	0.0184	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LEU-GLY-LEU-D	0.0208	1
GUINEA PIG COLLAGEN TYPE I	0.0006	1
HUMAN COLLAGEN TYPE I	0.0007	1
HUMAN COLLAGEN TYPE II	0.0011	1
HUMAN COLLAGEN TYPE III	0.0018	1

UniProt features (64 total): binding site 21, strand 14, sequence variant 8, glycosylation site 5, repeat 4, helix 3, sequence conflict 2, signal peptide 1, propeptide 1, chain 1, disulfide bond 1, turn 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
1I76	X-RAY DIFFRACTION	1.2
4QKZ	X-RAY DIFFRACTION	1.2
5H8X	X-RAY DIFFRACTION	1.3
1I73	X-RAY DIFFRACTION	1.4
2OY2	X-RAY DIFFRACTION	1.5
1ZS0	X-RAY DIFFRACTION	1.56
3DPE	X-RAY DIFFRACTION	1.6
1BZS	X-RAY DIFFRACTION	1.7
2OY4	X-RAY DIFFRACTION	1.7
1KBC	X-RAY DIFFRACTION	1.8
1ZP5	X-RAY DIFFRACTION	1.8
1JAP	X-RAY DIFFRACTION	1.82
1ZVX	X-RAY DIFFRACTION	1.87
3TT4	X-RAY DIFFRACTION	1.88
1A85	X-RAY DIFFRACTION	2
1A86	X-RAY DIFFRACTION	2
1JJ9	X-RAY DIFFRACTION	2
3DNG	X-RAY DIFFRACTION	2
1MMB	X-RAY DIFFRACTION	2.1
1MNC	X-RAY DIFFRACTION	2.1
3DPF	X-RAY DIFFRACTION	2.1
1JAO	X-RAY DIFFRACTION	2.4
1JAQ	X-RAY DIFFRACTION	2.4
1JAN	X-RAY DIFFRACTION	2.5
1JH1	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22894-F1	90.56	0.81

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 (1): 218

Ligand- & substrate-binding residues (21): 157; 167; 169; 174; 175; 177; 179; 182; 189; 191; 193; 195 …

Disulfide bonds (1): 279–464

Glycosylation sites (5): 54, 73, 112, 204, 246

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-6798695	Neutrophil degranulation
R-HSA-1474244	Extracellular matrix organization
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 215 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, chr11q22, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (10): proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), positive regulation of tumor necrosis factor production (GO:0032760), endodermal cell differentiation (GO:0035987), cellular response to lipopolysaccharide (GO:0071222), positive regulation of neuroinflammatory response (GO:0150078), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), positive regulation of microglial cell activation (GO:1903980)

GO Molecular Function (9): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), zinc ion binding (GO:0008270), tumor necrosis factor binding (GO:0043120), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), specific granule lumen (GO:0035580), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	1
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidase activity	2
endopeptidase activity	2
protein metabolic process	1
cellular component disassembly	1
extracellular matrix organization	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
endoderm formation	1
cell differentiation	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
positive regulation of inflammatory response	1
neuroinflammatory response	1
regulation of neuroinflammatory response	1
positive regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
microglial cell activation	1
positive regulation of macrophage activation	1
positive regulation of neuroinflammatory response	1
regulation of microglial cell activation	1
metallopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
cytokine binding	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1
secretory granule lumen	1
specific granule	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP8	SERPINH1	P29043	862
MMP8	TIMP2	P16035	831
MMP8	TIMP4	Q99727	813
MMP8	TIMP1	P01033	809
MMP8	TCN1	P20061	742
MMP8	MPO	P05164	736
MMP8	LCN2	P30150	733
MMP8	TIMP3	P35625	729
MMP8	A2M	P01023	724
MMP8	LTF	P02788	705
MMP8	IL10	P22301	681
MMP8	ELANE	P08246	674
MMP8	IL1B	P01584	667
MMP8	DEFA4	P12838	650
MMP8	IL6	P05231	636

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): MMP8 (Biochemical Activity), MMP8 (Synthetic Lethality), BCAN (Biochemical Activity), MMP8 (Affinity Capture-MS), MMP8 (Affinity Capture-MS), MMP8 (Affinity Capture-MS), MMP8 (Affinity Capture-MS), MMP8 (Negative Genetic), MMP8 (Negative Genetic), MMP8 (Negative Genetic), MMP8 (Negative Genetic), MMP9 (Negative Genetic), MMP8 (Negative Genetic), MMP8 (Negative Genetic), MMP8 (Negative Genetic)

ESM2 similar proteins: B3EWZ3, B3EWZ5, B3EWZ6, F7J220, O13065, O18783, O43897, O57382, O57460, O70138, O70244, O88354, O88766, P00747, P06867, P06868, P11214, P19637, P20918, P22894, P25723, P28826, P33434, P33436, P42664, P42674, P50903, P55114, P81139, P98060, P98068, P98070, P98072, P98073, Q01177, Q02157, Q06561, Q11174, Q16820, Q19204

Diamond homologs: D0EM77, G5EBU3, O04529, O13065, O18733, O18767, O18927, O23507, O35548, O44836, O54732, O55123, O55761, O60882, O62806, O70138, O75900, O77656, O88272, O88676, O88766, O93470, P03956, P03957, P07152, P08253, P08254, P09237, P09238, P13943, P14780, P21692, P22757, P22894, P23097, P24347, P28053, P28862, P28863, P29136

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MMP8	“down-regulates quantity by destabilization”	FGA	cleavage
MMP8	up-regulates	ECM_disassembly
MMP8	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	63
Likely benign	10
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
17113	MMP8, HAPLOTYPE, TGG	Pathogenic

SpliceAI

1377 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102713455:AATC:A	acceptor_loss	1.0000
11:102713456:ATCT:A	acceptor_loss	1.0000
11:102713457:TC:T	acceptor_loss	1.0000
11:102713458:C:CC	acceptor_gain	1.0000
11:102713459:T:C	acceptor_loss	1.0000
11:102713748:A:AC	donor_gain	1.0000
11:102713748:ACT:A	donor_loss	1.0000
11:102713749:C:CC	donor_gain	1.0000
11:102713750:T:TC	donor_loss	1.0000
11:102713751:T:TG	donor_loss	1.0000
11:102713752:A:AC	donor_gain	1.0000
11:102713752:AC:A	donor_loss	1.0000
11:102713752:ACGTT:A	donor_gain	1.0000
11:102713753:C:CA	donor_gain	1.0000
11:102713753:CG:C	donor_gain	1.0000
11:102713753:CGTT:C	donor_gain	1.0000
11:102713753:CGTTC:C	donor_gain	1.0000
11:102713853:CATAT:C	acceptor_gain	1.0000
11:102713855:TAT:T	acceptor_gain	1.0000
11:102714591:A:AC	donor_gain	1.0000
11:102714592:C:CC	donor_gain	1.0000
11:102714592:CTT:C	donor_gain	1.0000
11:102714594:T:TA	donor_gain	1.0000
11:102715299:GTTA:G	donor_loss	1.0000
11:102715300:TTAC:T	donor_loss	1.0000
11:102715301:TA:T	donor_loss	1.0000
11:102715302:A:AG	donor_loss	1.0000
11:102721397:TTA:T	donor_loss	1.0000
11:102721398:TACTT:T	donor_loss	1.0000
11:102721399:A:AC	donor_gain	1.0000

AlphaMissense

3112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102721471:A:C	F184L	0.996
11:102721471:A:T	F184L	0.996
11:102721473:A:G	F184L	0.996
11:102721417:C:A	W202C	0.995
11:102721417:C:G	W202C	0.995
11:102721504:A:C	F173L	0.995
11:102721504:A:T	F173L	0.995
11:102721506:A:G	F173L	0.995
11:102722452:C:A	W108C	0.995
11:102722452:C:G	W108C	0.995
11:102718517:G:C	H227Q	0.994
11:102718517:G:T	H227Q	0.994
11:102718544:T:A	E218D	0.993
11:102718544:T:G	E218D	0.993
11:102721419:A:G	W202R	0.993
11:102721419:A:T	W202R	0.993
11:102721505:A:C	F173C	0.993
11:102718493:C:A	M235I	0.992
11:102718493:C:G	M235I	0.992
11:102718493:C:T	M235I	0.992
11:102718535:A:C	H221Q	0.992
11:102718535:A:T	H221Q	0.992
11:102721692:A:G	W140R	0.992
11:102721692:A:T	W140R	0.992
11:102722504:C:G	C91S	0.992
11:102722505:A:T	C91S	0.992
11:102714611:C:G	A379P	0.991
11:102716345:C:G	A287P	0.991
11:102718441:C:G	D253H	0.991
11:102718537:G:C	H221D	0.991

dbSNP variants (sampled 300 via entrez): RS1000241599 (11:102722345 T>C,G), RS1000421644 (11:102723065 A>G), RS1000504777 (11:102723514 C>T), RS1000980883 (11:102723850 G>A), RS1001042353 (11:102718339 G>A), RS1001181956 (11:102714183 A>G), RS1001329629 (11:102719447 A>G), RS1001400344 (11:102719742 A>G), RS1001675906 (11:102713946 C>G), RS1001911813 (11:102720531 G>A), RS1001920513 (11:102725715 T>C), RS1001986673 (11:102724628 T>C), RS1002231315 (11:102725027 A>G), RS1002438353 (11:102725503 T>C), RS1002605075 (11:102724828 G>C)

Disease associations

OMIM: gene MIM:120355 | disease phenotypes: MIM:610504

GenCC curated gene-disease

Mondo (1): preterm premature rupture of the membranes (MONDO:0012511)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001942_2	Prostate cancer	2.000000e-11
GCST002547_6	Epilepsy	2.000000e-08
GCST006585_246	Blood protein levels	2.000000e-14

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563032	Preterm Premature Rupture of the Membranes (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095216 (PROTEIN FAMILY), CHEMBL4588 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 181,735 (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
CHEMBL1200699	DOXYCYCLINE	4	93,821
CHEMBL1350	TILUDRONIC ACID	4	14,784
CHEMBL4303669	ZOLEDRONIC ACID	4	523
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL75094	PRINOMASTAT	3	8,839
CHEMBL115653	CIPEMASTAT	2	359
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL279786	BATIMASTAT	2	21,247
CHEMBL440498	CTS-1027	2	615
CHEMBL4859268	AGG-523	1	35

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
SL422	Inhibition	9.3	pKi
ONO-4817	Inhibition	9.0	pKi
ilomastat	Inhibition	8.96	pIC50
marimastat	Inhibition	8.89	pIC50
CGS-27023A	Inhibition	8.11	pIC50
MMP13 tracer [18F]5j	Inhibition	5.92	pIC50
TP0556351	Inhibition	5.43	pIC50
doxycycline	Inhibition	4.6	pIC50

Binding affinities (BindingDB)

203 measured of 262 human assays (262 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-hydroxy-1-(2-methoxyethyl)-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide hydrochloride	KI	0.1 nM
1-Cyclopropyl-N-hydroxy-4-{[4-(phenylthio)phenyl]-sulfonyl}piperidine-4-carboxamide Hydrochloride	KI	0.1 nM
N-Hydroxy-4-{[4-(phenoxyphenyl]sulfonyl}-1- (2-propynyl)4-piperidinecarboxamide, Monohydrochloride	KI	0.13 nM
N-hydroxy-1-[(3-methoxyphenyl)methyl]-4-{[(4-phenoxybenzene)sulfonyl]methyl}piperidine-4-carboxamide hydrochloride	KI	0.2 nM
1-cyclopropyl-N-hydroxy-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide hydrochloride	KI	0.2 nM
N-hydroxy-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide	KI	0.22 nM
N-hydroxy-4-{[(4-phenoxybenzene)sulfonyl]methyl}-1-(prop-2-yn-1-yl)piperidine-4-carboxamide hydrochloride	KI	0.25 nM
N-Hydroxy-4-{[(4-phenoxyphenyl)sulfonyl]methyl}-1-(2-phenylethyl)piperidine-4-carboxamide Hydrochloride	KI	0.3 nM
N-hydroxy-1-(2-methoxyethyl)-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide hydrochloride	KI	0.3 nM
N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}-1-(prop-2-yn-1-yl)piperidine-4-carboxamide hydrochloride	KI	0.33 nM
alpha-tetrahydropyran beta-sulfone 1B	KI	0.4 nM
1-acetyl-N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	0.4 nM
N-Hydroxy-1-methyl-4-{[4-(phenylthio)phenyl]sulfonyl}-piperidine-4-carboxamide Hydrochloride	KI	0.5 nM
N-Pentafluorophenylsulfonyl-N-4-nitrobenzyl-glycine hydroxamate	KI	0.7 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	0.7 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	0.8 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	0.8 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}propanamide	KI	0.8 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxypropanamide	KI	0.9 nM
4-({[4-(3,4-Dimethylphenoxy)phenyl]sulfonyl}methyl)-N-hydroxy-1-prop-2-ynylpiperidine-4-carboxamide Hydrochloride	KI	0.9 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}acetamide	KI	1.4 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	1.4 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxyacetamide	KI	1.5 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}acetamide	KI	1.5 nM
2-{(2-chlorophenyl)methylsulfonamido}-N-hydroxypropanamide	KI	1.5 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	1.9 nM
N-hydroxy-1-methanesulfonyl-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	2 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	2.4 nM
N-hydroxy-4-{[(4-phenoxybenzene)sulfonyl]methyl}piperidine-4-carboxamide hydrochloride	KI	2.8 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}propanamide	KI	2.9 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxypropanamide	KI	3.2 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}acetamide	KI	3.7 nM
2-{(2-chlorophenyl)methylsulfonamido}-N-hydroxypropanamide	KI	3.7 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxyacetamide	KI	3.9 nM
(R)-[1-(4-Methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonic Acid	KI	5 nM
2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	10 nM
N-4-Methoxyphenylsulfonyl-N-benzyl-L-valine hydroxamate	KI	11 nM
hydroxamate deriv. B24	KI	12 nM
(4S)-5-[3-(carboxymethyl)piperidin-1-yl]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	12 nM	US-8691753
N-4-Methoxyphenylsulfonyl-N-2-nitrobenzyl-L-alanine hydroxamate	KI	13 nM
2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxypropanamide	KI	15 nM
N-hydroxy-2-[(4-methoxybenzene)[(2-nitrophenyl)methyl]sulfonamido]acetamide	KI	15 nM
N-hydroxy-2-[(4-methoxybenzene)[(4-nitrophenyl)methyl]sulfonamido]propanamide	KI	15 nM
CGS 27023A Analog 22	KI	18 nM
N-hydroxy-2-[(4-methoxybenzene)[(4-nitrophenyl)methyl]sulfonamido]acetamide	KI	18 nM
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	18.1 nM	US-8691753
2-{4-(but-2-yn-1-yloxy)benzenesulfonamido}-N-hydroxyacetamide	KI	27 nM
(4S)-5-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	31 nM	US-8691753
N-hydroxy-4-methyl-2-[(2,3,4,5,6-pentafluorobenzene)sulfonamido]pentanamide	KI	39 nM
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	39 nM	US-8691753

ChEMBL bioactivities

1372 potent at pChembl≥5 of 1606 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL2064547
10.52	IC50	0.03	nM	CHEMBL2064548
10.40	IC50	0.04	nM	CHEMBL2064549
10.34	IC50	0.046	nM	CHEMBL11306
10.30	IC50	0.05	nM	CHEMBL2425938
10.01	IC50	0.097	nM	CTS-1027
10.00	Ki	0.1	nM	CHEMBL293503
10.00	Ki	0.1	nM	CHEMBL306524
9.96	IC50	0.11	nM	CHEMBL2064542
9.96	Ki	0.11	nM	CHEMBL70417
9.74	Ki	0.18	nM	ILOMASTAT
9.70	IC50	0.2	nM	CHEMBL2064541
9.70	IC50	0.2	nM	CHEMBL439983
9.70	IC50	0.2	nM	CHEMBL2425943
9.70	IC50	0.2	nM	CHEMBL2425950
9.62	Ki	0.24	nM	CHEMBL71482
9.54	IC50	0.29	nM	CHEMBL471537
9.54	Ki	0.29	nM	CHEMBL310249
9.52	Ki	0.3	nM	CHEMBL123775
9.52	IC50	0.3	nM	CHEMBL2425944
9.52	IC50	0.3	nM	CHEMBL2425941
9.52	Ki	0.3	nM	CHEMBL70430
9.52	Ki	0.3	nM	CHEMBL68890
9.48	Ki	0.33	nM	CHEMBL302311
9.47	Ki	0.34	nM	CHEMBL306224
9.46	Ki	0.35	nM	CHEMBL420932
9.43	IC50	0.37	nM	CHEMBL227824
9.41	IC50	0.39	nM	CHEMBL227484
9.41	Ki	0.39	nM	CHEMBL422948
9.40	Ki	0.4	nM	CHEMBL281795
9.40	IC50	0.4	nM	CHEMBL4524116
9.40	IC50	0.4	nM	CHEMBL2425936
9.40	IC50	0.4	nM	CHEMBL2425947
9.40	IC50	0.4	nM	CHEMBL227501
9.40	IC50	0.4	nM	CHEMBL515980
9.40	IC50	0.4	nM	CHEMBL1801399
9.40	IC50	0.4	nM	CHEMBL1801054
9.40	IC50	0.4	nM	CHEMBL1801044
9.39	Ki	0.41	nM	CHEMBL70571
9.37	Ki	0.43	nM	CHEMBL70965
9.35	Ki	0.45	nM	CHEMBL419751
9.35	Ki	0.45	nM	CHEMBL306912
9.33	IC50	0.47	nM	MARIMASTAT
9.31	Ki	0.49	nM	CHEMBL306871
9.31	Ki	0.49	nM	CHEMBL72788
9.30	Ki	0.5	nM	CHEMBL285418
9.30	IC50	0.5	nM	CHEMBL2064552
9.30	Ki	0.5	nM	CHEMBL88520
9.30	Ki	0.5	nM	CHEMBL293357
9.30	IC50	0.5	nM	CHEMBL2425949

PubChem BioAssay actives

1340 with measured affinity, of 2082 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
(2R)-N’-hydroxy-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-2-(2-methylpropyl)butanediamide	362878: Inhibition of human recombinant MMP8	ic50	<0.0001	uM
(2R)-2-[[1-(2-fluoroethyl)triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	675789: Inhibition of MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	<0.0001	uM
2-[2-[2-[2-[4-[[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate	675789: Inhibition of MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	<0.0001	uM
(2R)-2-[[1-[2-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]ethyl]triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	675789: Inhibition of MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	<0.0001	uM
N-hydroxy-2-[(4-nitrophenyl)methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]acetamide	107977: Inhibitory activity against Matrix metalloprotease-8	ki	0.0001	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(pyridin-3-ylmethylamino)propan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0001	uM
(2R)-N’-hydroxy-N-[(2S)-1-[2-(4-hydroxyphenyl)ethylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0001	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162788: Inhibition of human recombinant MMP8 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0001	uM
(2R)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-[[4-[2-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethoxy]ethoxy]phenyl]methyl]amino]-3-methylbutanamide	675789: Inhibition of MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	0.0001	uM
(2R)-2-[[4-(2-fluoroethoxy)phenyl]sulfonyl-[2-[4-[4-[(2-fluoro-3-pyridinyl)oxy]butyl]triazol-1-yl]ethyl]amino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0001	uM
(2R)-2-hexyl-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0002	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-(2-methylpropyl)-3-(quinolin-8-ylmethylamino)butanediamide	107849: Inhibition of MMP-8 (matrix metalloprotease-8)	ic50	0.0002	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0002	uM
(2R)-2-[[4-[2-[2-[2-[2-[[1-(2-fluoroethyl)triazol-4-yl]methoxy]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	675789: Inhibition of MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	0.0002	uM
(2R)-2-[2-[4-[[(4-fluorophenyl)sulfonylamino]methyl]triazol-1-yl]ethyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0002	uM
(2R)-2-[[1-[2-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]ethyl]triazol-4-yl]methyl-[4-(2-fluoroethoxy)phenyl]sulfonylamino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0002	uM
(2R)-2-butyl-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0003	uM
(2R)-N’-hydroxy-N-[(2S)-1-(2-hydroxyethylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0003	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylmethylamino)propan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0003	uM
(2R)-N-[(2S)-1-(cyclopropylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0003	uM
N-hydroxy-2-[(4-nitrophenyl)methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]propanamide	107977: Inhibitory activity against Matrix metalloprotease-8	ki	0.0003	uM
(2R)-N-hydroxy-3-methyl-2-[[2-oxo-2-[2-(4-sulfamoylphenyl)ethylamino]ethyl]-(4-phenoxyphenyl)sulfonylamino]butanamide	413958: Inhibition of MMP8	ic50	0.0003	uM
(2R)-N’-hydroxy-2-(2-methylpropyl)-N-[(2R)-1-(3-morpholin-4-ylpropylamino)-3-naphthalen-1-yl-1-oxopropan-2-yl]butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0003	uM
(2R)-N’-hydroxy-N-[(2R)-1-[2-(4-hydroxyphenyl)ethylamino]-1-oxo-3-pyridin-4-ylpropan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0003	uM
(2R)-2-[[4-(2-fluoroethoxy)phenyl]sulfonyl-[[1-[2-[2-[2-[2-[(2-fluoro-3-pyridinyl)oxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methyl]amino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0003	uM
(2R)-2-[cyanomethyl-[4-(2-fluoroethoxy)phenyl]sulfonylamino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0003	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(pyridin-2-ylmethylamino)propan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0004	uM
(2S,3R)-N,2-dihydroxy-N’-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-3-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0004	uM
(2R)-N’-hydroxy-2-[(4-hydroxyphenyl)methyl]-N-[(2S)-3-(4-methoxyphenyl)-1-(methylamino)-1-oxopropan-2-yl]butanediamide	107980: Inhibition of matrix metalloprotease-8	ki	0.0004	uM
N-hydroxy-1-[(3-methoxyphenyl)methyl]-4-[(4-phenoxyphenyl)sulfonylmethyl]piperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0004	uM
N-hydroxy-4-(4-phenoxyphenyl)sulfonyloxane-4-carboxamide	604452: Inhibition of human MMP8 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0004	uM
2-[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-phenoxyphenyl)sulfonylamino]acetic acid	413958: Inhibition of MMP8	ic50	0.0004	uM
(2R)-N-[(2R)-3-(1-benzothiophen-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0004	uM
[(1R)-2-methyl-1-[[4-(4-methylphenyl)phenyl]sulfonylamino]propyl]phosphonic acid	284480: Inhibition of MMP8	ic50	0.0004	uM
[(1R)-1-[[4-(4-ethoxyphenyl)phenyl]sulfonylamino]-2-methylpropyl]phosphonic acid	284480: Inhibition of MMP8	ic50	0.0004	uM
[(1R)-2-methyl-1-[[4-(3-methylphenyl)phenyl]sulfonylamino]propyl]phosphonic acid	284480: Inhibition of MMP8	ic50	0.0004	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	107847: Inhibition of neutrophil collagenase (Matrix metalloprotease-8)	ic50	0.0004	uM
N-hydroxy-1-propan-2-yl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604452: Inhibition of human MMP8 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0004	uM
(2R)-2-[2-[4-(3-fluoropropyl)triazol-1-yl]ethyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0004	uM
(2R)-2-[[4-(2-fluoroethoxy)phenyl]sulfonyl-[2-[4-(3-fluoropropyl)triazol-1-yl]ethyl]amino]-N-hydroxy-3-methylbutanamide	769893: Inhibition of MMP-8 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	0.0004	uM
(1S,5R)-3-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-N-hydroxy-8-oxabicyclo[3.2.1]octane-3-carboxamide	107993: Inhibition of matrix metalloprotease-8	ic50	0.0004	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(3-morpholin-4-ylpropylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0004	uM
N-hydroxy-4-[4-[4-(trifluoromethylsulfanyl)phenoxy]phenyl]sulfonyloxane-4-carboxamide	604452: Inhibition of human MMP8 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0004	uM
2-[1-(2-methoxyethoxycarbonyl)piperidin-4-yl]-2-[[4-(4-methoxyphenyl)phenyl]sulfonylamino]acetic acid	107850: Inhibitory activity against matrix metalloprotease-8	ic50	0.0005	uM
(6S,7R,10S)-6-N-hydroxy-10-N-[2-(methylamino)-2-oxoethyl]-7-(2-methylpropyl)-8-oxo-2-oxa-9-azabicyclo[10.2.2]hexadeca-1(14),12,15-triene-6,10-dicarboxamide	107978: Inhibition of matrix metalloprotease-8	ki	0.0005	uM
2-[[4-[(4-fluorophenyl)sulfonylcarbamoylamino]phenyl]sulfonyl-[(4-nitrophenyl)methyl]amino]-N-hydroxyacetamide	108588: Inhibitory activity against the Matrix Metalloprotease-8	ki	0.0005	uM
(2R)-N-[(2S)-1-(furan-2-ylmethylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0005	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(2-pyridin-2-ylethylamino)propan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0005	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	107991: Inhibition of Matrix metalloprotease-8 (MMP-8) in fluorimetric assay	ic50	0.0005	uM
(2R)-N’-hydroxy-N-[(2R)-1-(methylamino)-1-oxo-3-quinolin-8-ylpropan-2-yl]-2-(2-methylpropyl)butanediamide	107987: The compound was tested for its binding affinity towards neutrophil collagenase (Matrix metalloprotease-8)	ki	0.0005	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases reaction, increases expression	3
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance, affects cotreatment, decreases expression	2
perfluorooctanoic acid	increases expression	1
1,10-phenanthroline	decreases activity	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
epigallocatechin gallate	decreases reaction, increases expression	1
3-hydroxypicolinic acid	decreases activity	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
CGS 27023A	affects activity	1
prinomastat	decreases activity	1
perfluorohexanesulfonic acid	increases expression	1
oligofectamine	increases expression	1
dieckol	decreases reaction, increases expression	1
diphlorethohydroxycarmalol	decreases reaction, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Aluminum Oxide	decreases expression	1
Calcitriol	increases expression	1
Doxycycline	decreases activity	1
Edetic Acid	decreases activity	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases abundance, increases expression	1
Tetracycline	decreases activity	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1
Tretinoin	increases expression	1
Zinc	affects cotreatment, affects expression	1
Simvastatin	decreases reaction, increases expression	1

ChEMBL screening assays

238 unique, capped per target: 225 binding, 9 admet, 3 functional, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4481593	Binding	Inhibition of collagenase (unknown origin) at 200 uM relative to control	Deleting a Chromatin Remodeling Gene Increases the Diversity of Secondary Metabolites Produced by Colletotrichum higginsianum. — J Nat Prod
CHEMBL663111	Functional	In vitro antagonist activity against collagenase induced gel-filtered platelet (GFP) aggregation at 50 uM; NA=Inactive	Discovery and optimization of a novel series of thrombin receptor (par-1) antagonists: potent, selective peptide mimetics based on indole and indazole templates. — J Med Chem
CHEMBL1738687	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development efforts to identify inhibitors of Matrix Metalloprotease-13 (MMP-13). (Class of assay: screening) [Related pubchem assays (depositor defined):AID1931, AID570, AID734, AID735, A	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7YB	Abcam Raji MMP8 KO	Cancer cell line	Male
CVCL_B9Z1	Abcam THP-1 MMP8 KO	Cancer cell line	Male
CVCL_C7AR	Abcam PC-3 MMP8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05322252	PHASE4	COMPLETED	Simultaneous Mifepristone and Misoprostol Versus Misoprostol Alone for Induction of Labor of Nonviable Second Trimester Pregnancy: a Pilot Randomized Controlled Trial
NCT01401179	PHASE3	COMPLETED	Antibiotics Study in Preterm Premature Rupture of the Membranes
NCT02939742	PHASE2/PHASE3	TERMINATED	Does a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?
NCT00397735	PHASE1/PHASE2	COMPLETED	N-acetylcysteine in Intra-amniotic Infection/Inflammation
NCT02069587	Not specified	UNKNOWN	Pomegranate to Reduce Maternal and Fetal Oxidative Stress and to Improve Outcome in Pregnancies Complicated With Preterm Premature Rupture of Membranes
NCT02327637	Not specified	TERMINATED	A Comparison of Bed Rest Versus Moderate Activity in Preterm Premature Rupture of Membranes (PPROM)
NCT02386644	Not specified	COMPLETED	Transperineal Ultrasonography and Premature Rupture of Membranes
NCT02997345	Not specified	RECRUITING	PPROM Registry (Preterm Premature Rupture of Membranes)
NCT03739463	Not specified	UNKNOWN	Pro-omega-3, Reduction of Inflammation and Modulation of Prematurity
NCT03819192	Not specified	UNKNOWN	Predicting EONS in PPROM Patients
NCT04230967	Not specified	COMPLETED	Ambulation for Latency During Expectant Management of PPROM
NCT05773014	Not specified	RECRUITING	Digital vs. Speculum Exams for PPROM
NCT06443788	Not specified	COMPLETED	Trans-perineal Ultrasound in Assessment of PPROMs
NCT06878443	Not specified	WITHDRAWN	Vaginal Probiotics During Pregnancy After Premature Rupture of Membranes
NCT06906757	Not specified	NOT_YET_RECRUITING	Preterm Rupture of Membranes Optimising Antibiotics Trial
NCT06965049	Not specified	NOT_YET_RECRUITING	Vaginal Probiotics During Pregnancy After Premature (24-32 Weeks of Gestation) Preterm Rupture of Membranes
NCT07191366	Not specified	NOT_YET_RECRUITING	Antenatal Breastmilk Expression in Pregnant Women at High Risk of Preterm Birth