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
• GTEx eGene: eQTL in 4 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 3 curated mechanism-of-action drugs; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Doxycycline
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.46 (unconstrained)
• MANE Select transcript: NM_002424
• Notable: 84 clinical variants but no curated precision-oncology (CIViC) evidence yet

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

MANE Select: ENST00000236826

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 3, TSL 5: 2

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.

Highest expression (Bgee): trabecular bone tissue, bone marrow, bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MMP8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	1.8e-02	-0.19	11:102691969:C:T
Whole Blood	eqtl	3.4e-02	+0.32	11:102684301:A:C
Artery Tibial	eqtl	4.9e-02	+0.20	11:102512513:C:T
Thyroid	eqtl	5.0e-02	+0.32	11:103726369:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
121984	2.5258	130

Top tissues by expression

showing 100 of 273 tissues 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
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
nasal cavity epithelium	UBERON:0005384	50.01	gold quality
right lobe of liver	UBERON:0001114	49.76	gold quality
muscle tissue	UBERON:0002385	49.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
layer of synovial tissue	UBERON:0007616	48.57	gold quality
upper leg skin	UBERON:0004262	48.55	silver quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
kidney epithelium	UBERON:0004819	47.99	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
ileal mucosa	UBERON:0000331	47.50	silver quality
liver	UBERON:0002107	47.49	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
omental fat pad	UBERON:0010414	46.94	gold quality
peritoneum	UBERON:0002358	46.92	gold quality
placenta	UBERON:0001987	46.89	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
descending thoracic aorta	UBERON:0002345	46.71	gold quality
lymph node	UBERON:0000029	46.67	gold quality
adipose tissue of abdominal region	UBERON:0007808	46.59	gold quality
vermiform appendix	UBERON:0001154	46.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	46.24	silver quality
visceral pleura	UBERON:0002401	46.11	silver quality
subcutaneous adipose tissue	UBERON:0002190	46.03	gold quality
oocyte	CL:0000023	46.01	gold quality
connective tissue	UBERON:0002384	45.99	gold quality
caecum	UBERON:0001153	45.75	gold quality
stromal cell of endometrium	CL:0002255	45.60	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
adipose tissue	UBERON:0001013	45.31	gold quality
heart left ventricle	UBERON:0002084	45.30	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
cardiac ventricle	UBERON:0002082	45.12	gold quality
palpebral conjunctiva	UBERON:0001812	44.31	gold quality
muscle organ	UBERON:0001630	43.90	gold quality
cranial nerve II	UBERON:0000941	43.82	silver quality
skin of hip	UBERON:0001554	43.75	silver quality
trachea	UBERON:0003126	43.44	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	43.06	gold quality
heart	UBERON:0000948	43.00	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
epithelium of bronchus	UBERON:0002031	42.87	gold quality
bronchus	UBERON:0002185	42.75	gold quality
pleura	UBERON:0000977	42.68	silver quality
cartilage tissue	UBERON:0002418	42.59	gold quality
kidney	UBERON:0002113	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
colonic epithelium	UBERON:0000397	42.47	gold quality
gastrocnemius	UBERON:0001388	42.38	gold quality
right lobe of thyroid gland	UBERON:0001119	42.18	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

HPA expression

RNA tissue specificity: Tissue enriched

25 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	473.9	high
Thymus	tissue	2.4
Endometrium 1	tissue	1.8	not detected
Spleen	tissue	0.7	high
Placenta	tissue	0.6	not detected
Skin 1	tissue	0.5	not detected
Choroid plexus	tissue	0.5
Liver	tissue	0.4	not detected
Appendix	tissue	0.3	not detected
Adipose tissue	tissue	0.2	not detected
Salivary gland	tissue	0.2	not detected
Smooth muscle	tissue	0.2	not detected
Substantia nigra	tissue	0.2
Pituitary gland	tissue	0.1
Lymph node	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected
Nucleus accumbens	tissue	0.1
Locus coeruleus	tissue	0.1
Spinal cord	tissue	0.1
Hippocampus	tissue	0.1	not detected
Corpus callosum	tissue	0.1
Postcentral gyrus	tissue	0.1
Ventral forebrain	tissue	0.1
Periaqueductal gray	tissue	0.1
Septum	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 172; highest nTPM — Anterior thalamic nucleus, ventral (1.6), Temporo-occipital transitional zone (0.6), Centromedial thalamic nucleus (0.5), Dorsal cochlear nucleus (0.5), Spinal trigeminal nucleus, oral (0.5).

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)

Targeting MMP8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 80 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.01e-22, LOEUF 1.46, missense Z -1.35 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000236826 — one region, missense o/e 1.17.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1202395) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal inflammatory response	1
increased papilloma incidence	1
increased tumor incidence	1
increased susceptibility to bacterial infection	1
chronic inflammation	1
decreased circulating free fatty acids level	1
increased heart weight	1
increased fibrosarcoma incidence	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
Pongo abelii	Q5RES1	98.8%	Diamond
Sus scrofa	Q9XT90	96.7%	Diamond
Oryctolagus cuniculus	P50757	95.2%	Diamond
Bos taurus	Q9GLE4	95.2%	Diamond
Equus caballus	O18927	90.5%	Diamond
Tupaia belangeri	Q9GKE1	85.2%	Diamond
Canis lupus familiaris	Q6Y4Q5	78.9%	Diamond
Aquarana catesbeiana	Q11133	75.3%	Diamond
Felis catus	P55032	72.5%	Diamond
Arabidopsis thaliana	Q5XF51	71.1%	Diamond
Paracentrotus lividus	P22757	70.4%	Diamond
Xenopus laevis	Q10835	69.4%	Diamond
Glycine max	P29136	48.7%	Diamond
Tannerella forsythia 92A2	D0EM77	45.2%	Diamond
Spodoptera frugiperda ascovirus 1a	Q0E587	59.2%	Diamond
Invertebrate iridescent virus 6	O55761	46.9%	Diamond
Invertebrate iridescent virus 3	Q196W5	43.3%	Diamond
Trichoplusia ni ascovirus 2c	Q06VC5	41.0%	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
MMP1	protein-coding	4312
MMP10	protein-coding	4319
MMP27	protein-coding	64066
MMP7	protein-coding	4316
MMP20	protein-coding	9313
MMP20-AS1	ncRNA	101928477

Protein

Protein identifiers

Neutrophil collagenase — P22894 (reviewed: P22894)

Alternative names: Matrix metalloproteinase-8, PMNL collagenase

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

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 by resolution:

PDB	Title	Method	Resolution (Å)
1I76	COMPLEX OF 2-(BIPHENYL-4-SULFONYL)-1,2,3,4-TETRAHYDRO-ISOQUINOLINE-3-CARBOXYLIC ACID …	X-RAY DIFFRACTION	1.2
4QKZ	X-ray structure of the catalytic domain of MMP-8 with the inhibitor ML115	X-RAY DIFFRACTION	1.2
5H8X	Crystal structure of the complex MMP-8/BF471 (catechol inhibitor)	X-RAY DIFFRACTION	1.3
1I73	COMPLEX OF PRO-LEU-L-TRP PHOSPHONATE WITH THE CATALITIC DOMAIN OF MATRIX METALLO …	X-RAY DIFFRACTION	1.4
2OY2	Human MMP-8 in complex with peptide IAG	X-RAY DIFFRACTION	1.5
1ZS0	Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)	X-RAY DIFFRACTION	1.56
3DPE	Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor	X-RAY DIFFRACTION	1.6
1BZS	CRYSTAL STRUCTURE OF MMP8 COMPLEXED WITH HMR2909	X-RAY DIFFRACTION	1.7
2OY4	Uninhibited human MMP-8	X-RAY DIFFRACTION	1.7
1KBC	PROCARBOXYPEPTIDASE TERNARY COMPLEX	X-RAY DIFFRACTION	1.8
1ZP5	Crystal structure of the complex between MMP-8 and a N-hydroxyurea inhibitor	X-RAY DIFFRACTION	1.8
1JAP	COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO …	X-RAY DIFFRACTION	1.82
1ZVX	Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (R-enantiomer)	X-RAY DIFFRACTION	1.87
3TT4	Human MMP8 in complex with L-glutamate motif inhibitor	X-RAY DIFFRACTION	1.88
1A85	MMP8 WITH MALONIC AND ASPARAGINE BASED INHIBITOR	X-RAY DIFFRACTION	2
1A86	MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR	X-RAY DIFFRACTION	2
1JJ9	Crystal Structure of MMP8-Barbiturate Complex Reveals Mechanism for Collagen Substrate …	X-RAY DIFFRACTION	2
3DNG	Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor	X-RAY DIFFRACTION	2
1MMB	COMPLEX OF BB94 WITH THE CATALYTIC DOMAIN OF MATRIX METALLOPROTEINASE-8	X-RAY DIFFRACTION	2.1
1MNC	STRUCTURE OF HUMAN NEUTROPHIL COLLAGENASE REVEALS LARGE S1’ SPECIFICITY POCKET	X-RAY DIFFRACTION	2.1
3DPF	Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor	X-RAY DIFFRACTION	2.1
1JAO	COMPLEX OF 3-MERCAPTO-2-BENZYLPROPANOYL-ALA-GLY-NH2 WITH THE CATALYTIC DOMAIN OF MATRIX …	X-RAY DIFFRACTION	2.4
1JAQ	COMPLEX OF 1-HYDROXYLAMINE-2-ISOBUTYLMALONYL-ALA-GLY-NH2 WITH THE CATALYTIC DOMAIN OF …	X-RAY DIFFRACTION	2.4
1JAN	COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO …	X-RAY DIFFRACTION	2.5
1JH1	Crystal Structure of MMP-8 complexed with a 6H-1,3,4-thiadiazine derived inhibitor	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Metallopeptidases, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
218

Ligand- & substrate-binding residues (21)

Position	Role
157	Ca(2+)
167	Zn(2+)
169	Zn(2+)
174	Ca(2+)
175	Ca(2+)
177	Ca(2+)
179	Ca(2+)
182	Zn(2+)
189	Ca(2+)
191	Ca(2+)
193	Ca(2+)
195	Zn(2+)
197	Ca(2+)
200	Ca(2+)
217	Zn(2+)
221	Zn(2+)
227	Zn(2+)
286	Ca(2+)
378	Ca(2+)
425	Ca(2+)
91	Zn(2+)

Disulfide bonds (1)

Type	Positions
Disulfide bond	279–464

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	54, 73, 112, 204, 246

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-1592389	Activation of Matrix Metalloproteinases	curated
R-HSA-1442490	Collagen degradation	curated
R-HSA-1474228	Degradation of the extracellular matrix	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate 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 (4): extracellular region (GO:0005576), extracellular matrix (GO:0031012), specific granule lumen (GO:0035580), tertiary granule lumen (GO:1904724)

Reactome top-level categories

4 top-level categories:

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

GO top-level categories

42 GO namespaces:

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
intracellular organelle lumen	1
tertiary granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
endodermal cell differentiation	BP	expression pattern
positive regulation of tumor necrosis factor production	BP	mutant phenotype
proteolysis	BP	direct assay
extracellular matrix	CC	high-throughput assay
endopeptidase activity	MF	mutant phenotype
peptidase activity	MF	direct assay
serine-type endopeptidase activity	MF	direct assay
tumor necrosis factor binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,494 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP8	SERPINH1	P29043	861
MMP8	TIMP1	P01033	775
MMP8	MTF2	Q9Y483	758
MMP8	TIMP2	P16035	719
MMP8	TIMP4	Q99727	696
MMP8	IL1B	P01584	676
MMP8	ELANE	P08246	665
MMP8	TCN1	P20061	665
MMP8	IL6	P05231	653
MMP8	CDK5	Q00535	630
MMP8	TNF	P01375	611
MMP8	CXCL8	P10145	610
MMP8	ELN	P15502	596
MMP8	TIMP3	P35625	594
MMP8	MPO	P05164	593

IntAct

BioGRID (19 interactions; top human partners by supporting records): BCAN (Biochemical Activity), CSK (Synthetic Lethality), FBXO7 (Biochemical Activity), GNG8 (Affinity Capture-MS), KLK10 (Affinity Capture-MS), MMP1 (Negative Genetic), MMP11 (Negative Genetic), MMP13 (Negative Genetic), MMP15 (Negative Genetic), MMP16 (Negative Genetic), MMP2 (Negative Genetic), MMP20 (Negative Genetic), MMP24 (Negative Genetic), MMP25 (Negative Genetic), MMP27 (Negative Genetic)

SIGNOR signaling

showing 3 of 4 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for MMP8: 84 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

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)

Showing all 1 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
17113	MMP8, HAPLOTYPE, TGG	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore MMP8’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; 36 predictions of 721):

Position(s)	Effect	Δscore	Sites
11:102713458–102713459	acceptor_loss	1.0000	5
11:102713752–102713753	donor_loss	1.0000	5
11:102715302–102715303	donor_loss	1.0000	5
11:102721399–102721400	donor_loss	1.0000	3
11:102721527–102721528	acceptor_loss	1.0000	2
11:102713458	acceptor_loss	0.9900
11:102713858–102713859	acceptor_loss	0.9900	6
11:102715438–102715439	acceptor_loss	0.9900	4
11:102715448	acceptor_gain	0.9900
11:102716300–102716301	donor_loss	0.9900	4

AlphaMissense

841 missense substitutions predicted likely pathogenic (of 3,112 scored), across 210 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
M235	9	0.931	0.992
H221	8	0.981	0.992
H217	8	0.976	0.991
D253	8	0.975	0.991
F173	8	0.974	0.995
H227	8	0.973	0.994
H182	8	0.968	0.987
D169	8	0.956	0.981
H195	8	0.948	0.982
H167	8	0.935	0.979
D197	8	0.935	0.971
F162	8	0.926	0.990
F196	8	0.900	0.990
D95	8	0.889	0.958
D174	8	0.880	0.942
D193	8	0.874	0.934
F344	8	0.853	0.966
F390	8	0.838	0.932
F298	8	0.798	0.965
E218	7	0.983	0.993

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Skin Cutaneous Melanoma)

Disease associations

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

GenCC curated gene-disease

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

GWAS associations

3 associations:

Study	Trait	p-value
GCST006585_1974	Blood protein levels	2e-14
GCST001942_2	Prostate cancer	2e-11
GCST002547_6	Epilepsy	2e-8

MeSH disease descriptors

1 disease descriptors:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MMP8 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.

3 curated-mechanism drugs:

Drug	Modality	Max phase
DOXYCYCLINE	Small molecule	4
CTS-1027	Small molecule	2
REBIMASTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 183,707 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1200699	DOXYCYCLINE	4	94,976
CHEMBL1350	TILUDRONIC ACID	4	14,868
CHEMBL4303669	ZOLEDRONIC ACID	4	528
CHEMBL279785	MARIMASTAT	3	29,705
CHEMBL75094	PRINOMASTAT	3	8,942
CHEMBL440498	CTS-1027	2	651
CHEMBL279786	BATIMASTAT	2	21,436
CHEMBL115653	CIPEMASTAT	2	380
CHEMBL19611	ILOMASTAT	2	12,186
CHEMBL4859268	AGG-523	1	35

PharmGKB: 1 entry (CPIC guideline: no)

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)

1328 measured of 1502 human assays (1506 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
alpha-tetrahydropyran beta-sulfone 1B	IC50	0.029 nM
CHEMBL5412341	IC50	0.034 nM
CHEMBL5288452	IC50	0.0449 nM
AG-3340	IC50	0.048 nM
CHEMBL5182207	IC50	0.055 nM
CHEMBL5185612	IC50	0.068 nM
CHEMBL2064548	IC50	0.07 nM
(R)-2-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-N-hydroxy-3-methyl-butyramide	IC50	0.09 nM
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
CHEMBL1801396	IC50	0.1 nM
CHEMBL1801424	IC50	0.1 nM
CHEMBL1801413	IC50	0.1 nM
CHEMBL1229868	IC50	0.1 nM
CHEMBL1801050	IC50	0.1 nM
CHEMBL1801044	IC50	0.1 nM
CHEMBL2064549	IC50	0.1 nM
(R)-N*4*-Hydroxy-N*1*-[2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide	IC50	0.104 nM
N-Hydroxy-4-{[4-(phenoxyphenyl]sulfonyl}-1- (2-propynyl)4-piperidinecarboxamide, Monohydrochloride	KI	0.13 nM
CHEMBL2064547	IC50	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
N4-HYDROXY-2-ISOBUTYL-N1-(9-OXO-1,8-DIAZA-TRICYCLO[10.6.1.013,18]NONADECA-12(19),13,15,17-TETRAEN-10-YL)-SUCCINAMIDE	KI	0.2 nM
CHEMBL1801431	IC50	0.2 nM
CHEMBL1801428	IC50	0.2 nM
CHEMBL1801427	IC50	0.2 nM
CHEMBL1801423	IC50	0.2 nM
CHEMBL1801420	IC50	0.2 nM
CHEMBL1801057	IC50	0.2 nM
CHEMBL2064552	IC50	0.2 nM
CHEMBL5169565	IC50	0.2 nM
(R)-2-Hexyl-N*4*-hydroxy-N*1*-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-succinamide	KI	0.21 nM
N-hydroxy-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide	KI	0.22 nM
(2R,3S)-N*1*-((S)-2,2-Dimethyl-1-methylcarbamoyl-propyl)-N*4*-hydroxy-2-isobutyl-3-[(quinolin-8-ylmethyl)-amino]-succinamide	IC50	0.23 nM
CHEMBL1801421	IC50	0.25 nM
3-[4-(4-Fluoro-phenoxy)-benzenesulfonylamino]-8-oxa-bicyclo[3.2.1]octane-3-carboxylic acid hydroxyamide	IC50	0.26 nM
N-Hydroxy-4-{[(4-phenoxyphenyl)sulfonyl]methyl}-1-(2-phenylethyl)piperidine-4-carboxamide Hydrochloride	IC50	0.3 nM
N-hydroxy-1-(2-methoxyethyl)-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide hydrochloride	KI	0.3 nM
(R)-N*1*-[(S)-1-Hexylcarbamoyl-2-(1H-indol-3-yl)-ethyl]-N*4*-hydroxy-2-isobutyl-succinamide	KI	0.3 nM
CHEMBL1801426	IC50	0.3 nM
CHEMBL1801045	IC50	0.3 nM
CHEMBL5199189	IC50	0.3 nM
(R)-N4-hydroxy-N1-((S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl)-2-(5-phenoxypentyl)succinamide	IC50	0.31 nM
N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}-1-(prop-2-yn-1-yl)piperidine-4-carboxamide hydrochloride	IC50	0.33 nM
N-(4-Phenoxybenzenesulfonyl)-N-{[2-(4-sulfamoylphenyl)ethylcarbamoyl]methyl}-D-valinehydroxamic Acid	IC50	0.35 nM
CHEMBL1801047	IC50	0.35 nM
CHEMBL2064542	IC50	0.35 nM
[(R)-1-(4’-ethoxy-biphenyl-4-sulfonylamino)-2-methyl-propyl]-phosphonic acid	IC50	0.39 nM
BOC-piperidinyl glycine derivative, 34	IC50	0.398 nM
1-acetyl-N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	0.4 nM

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

1341 with measured affinity, of 2083 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	increases expression, affects response to substance, affects cotreatment, decreases expression, decreases reaction	2
perfluorooctanoic acid	increases expression	1
1,10-phenanthroline	decreases activity	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases 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)

Via MONDO — disease-level, not drug-specific.

18 trials:

NCT	Phase	Status	Title
NCT05322252	Phase 4	COMPLETED	Simultaneous Mifepristone and Misoprostol Versus Misoprostol Alone for Induction of Labor of Nonviable Second Trimester Pregnancy: a Pilot Randomized Controlled Trial
NCT07669207	Phase 4	RECRUITING	Extended Azithromycin Treatment in Prelabor Rupture of Membranes
NCT01401179	Phase 3	COMPLETED	Antibiotics Study in Preterm Premature Rupture of the Membranes
NCT02939742	Phase 2/3	TERMINATED	Does a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?
NCT00397735	Phase 1/2	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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MMP8 across ~30M SureChEMBL compounds — explore on Sugi Predict.