MMP3

Summary

MMP3 (matrix metallopeptidase 3, HGNC:7173) is a protein-coding gene on chromosome 11q22.2, encoding Stromelysin-1 (P08254). Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans.

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.

Source: NCBI Gene 4314 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 109 total
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7173
Approved symbol	MMP3
Name	matrix metallopeptidase 3
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000149968
Ensembl biotype	protein_coding
OMIM	185250
Entrez	4314

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000299855, ENST00000434103, ENST00000524478

RefSeq mRNA: 1 — MANE Select: NM_002422 NM_002422

CCDS: CCDS8323

Canonical transcript exons

ENST00000299855 — 10 exons

Exon	Start	End
ENSE00001105420	102842154	102842279
ENSE00001105427	102840108	102840252
ENSE00001105439	102839110	102839243
ENSE00001105448	102837298	102837401
ENSE00001292630	102835801	102836226
ENSE00002171374	102843442	102843609
ENSE00002448882	102838551	102838710
ENSE00002477135	102840429	102840593
ENSE00003601812	102842672	102842916
ENSE00003674848	102842431	102842579

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 99.16.

FANTOM5 (CAGE): breadth broad, TPM avg 29.9682 / max 6404.1810, expressed in 440 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122025	29.9682	440

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.16	gold quality
cartilage tissue	UBERON:0002418	98.82	gold quality
pericardium	UBERON:0002407	98.42	gold quality
tendon of biceps brachii	UBERON:0008188	97.17	gold quality
synovial joint	UBERON:0002217	94.61	gold quality
synovial membrane of synovial joint	UBERON:0002018	94.12	gold quality
minor salivary gland	UBERON:0001830	94.08	gold quality
tendon	UBERON:0000043	93.66	gold quality
islet of Langerhans	UBERON:0000006	87.94	gold quality
mouth mucosa	UBERON:0003729	87.58	gold quality
stromal cell of endometrium	CL:0002255	86.97	gold quality
layer of synovial tissue	UBERON:0007616	85.43	gold quality
saliva-secreting gland	UBERON:0001044	83.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.04	gold quality
tibial nerve	UBERON:0001323	82.88	gold quality
vermiform appendix	UBERON:0001154	79.92	gold quality
skin of leg	UBERON:0001511	77.32	gold quality
gastrocnemius	UBERON:0001388	76.52	gold quality
periodontal ligament	UBERON:0008266	76.08	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.17	gold quality
caecum	UBERON:0001153	73.01	gold quality
muscle of leg	UBERON:0001383	71.92	gold quality
tongue squamous epithelium	UBERON:0006919	70.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.61	gold quality
body of stomach	UBERON:0001161	68.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	67.68	silver quality
rectum	UBERON:0001052	67.10	gold quality
epithelial cell of pancreas	CL:0000083	66.92	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	66.74	gold quality
zone of skin	UBERON:0000014	66.59	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	39992.32
E-MTAB-7052	yes	10105.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, CTSH, ERG, ESR1, ETS1, ETS2, ETV1, ETV6, ETV7, FOS, FOXC1, FOXO3, HIF1A, IL1B, JUN, JUNB, MAFB, NFKB1, NFKB, NFKBIA, NR3C1, NR4A2, RELA, SOX2, STAT3, TBP, TCF20, TCF3, UBTF, ZMYND8, ZNF148

miRNA regulators (miRDB)

37 targeting MMP3, 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-574-5P	100.00	66.01	989
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-5581-5P	97.91	66.50	965

Literature-anchored findings (GeneRIF, showing 40)

• induction in fibroblasts by basic calcium phosphate crystals (PMID:11836255)
• can cleave all subclasses of igG at a specific conserved site (PMID:11841844)
• The 6A6A MMP3 genotype is a genetic susceptibility factor for restenosis after angioplasty without stenting. (PMID:11977998)
• Stromelysin-1 activation correlates with invasiveness in squamous cell carcinoma (PMID:11982752)
• involvement of MAPKs, AP-1 and NF-kappa B transcription factors in the IL-1 induction of MMP-3 and MMP-13 in chondrocytes (PMID:12009331)
• destruction of the surrounding matrix by endometriosis might be caused by various MMPs, which are mainly produced in stromal cells. (PMID:12034345)
• cooperative binding of promoter with ETS-1 transcription factor (PMID:12034715)
• lack of expresion in Ewing sarcoma may be due to loss of accessibility of regulatory element to the specific fusion protein in vivo (PMID:12054564)
• Activation of protein kinase CK2 is an early step in the ultraviolet B-mediated increase in interstitial collagenase (matrix metalloproteinase-1; MMP-1) and stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts. (PMID:12071839)
• The severe coronary atherosclerotic lesions were significantly associated with the MMP3 genotype as an independent factor of the coronary lesions. (PMID:12204805)
• data provide evidence that MMP-3 can inhibit breast tumour cell invasion in vitro by a mechanism involving plasminogen degradation to fragments that limit plasminogen activation and the degradation of laminin (PMID:12230559)
• With regard to the MMP-3 polymorphism, unexpectedly, the frequency of the 6A/6A genotype causing lower enzyme activity was significantly increased in patients (p = 0.0129; OR = 2.110; 95% CI = 1.165-3.822). (PMID:12432557)
• A single nucleotide polymorphism in MMP-3 promoter is associated with invasive behaviour in breast cancer (PMID:12473595)
• The presence of this protein has a higher risk for arteriosclerosis in men who are smokers. (PMID:12485468)
• N-TIMP-1 interaction with the catalytic domain of MMP-3 investigation by titration calorimetry and 15N NMR (PMID:12634064)
• expression and regulation by intestinal myofibroblasts in inflammatory bowel disease (PMID:12651627)
• Data demonstrate that blockade of the ERK pathway suppressed the expression of matrix metalloproteinases 3, 9, and 14, and CD44, and markedly inhibited the invasiveness of tumor cells. (PMID:12727228)
• stromelysin-1, which has the ability to degrade the mucosal extra-cellular matrix, may be responsible for the extensive tissue injury in infants with necrotizing enterocolitis (PMID:12736398)
• Matrix metalloproteinase-3 polymorphism contributes to age-related aortic stiffening through modulation of gene and protein expression. (PMID:12750310)
• regulation of expression by ATP (PMID:12761889)
• The proliferative response to a MMP-3 epitope was similar in rheumatoid arthritis patients and controls; the MMP-3 epitope increased IL-4, and IL-1beta and tumor necrosis factor-a production of arthritis lymphocytes, but not cytokines in controls. (PMID:12784383)
• The increase in antigenic levels of uPA and MMP-3 in endometrium of women with endometriosis might contribute to the invasive potential of endometrial cells (PMID:12832381)
• MMP3 is a senescence-associated gene in normal human oral keratinocytes. (PMID:12837283)
• Increased matrix metalloproteinase-3 expression accounts for invasive properties of human astrocytoma cell lines (PMID:12866026)
• proteolysis of SPARC by MMP-3 produced peptides that regulate endothelial cell proliferation and influence angiogenesis (PMID:12867428)
• The present results indicate that MMP-2 can be helpful in diagnosing Takayasu arteritis [TA] and that MMP-3 and MMP-9 can be used as activity markers for TA (PMID:12952836)
• Cultured vascular smooth muscle cells infected with Chlamydia pneumoniae secreted increased quantities of MMP-3 protein (PMID:13129650)
• The observations are consistent with a downstream mediation role of MMP-3 in phosphoglucose isomerase/AMF-stimulated tumor cell metastasis. (PMID:14715248)
• The results suggest that the 5A/6A polymorphism of MMP-3 gene may not be linked with appearance and/or progression of ovarian cancer. (PMID:14998290)
• Polymorphism is not associated with myocardial infarct in Japan. (PMID:15009479)
• MMP3, MMP9, and TGFbeta1 are important for the modulation, composition, and maintenance of the ECM in oral squamous cell carcinoma (PMID:15033492)
• cleaves IGFBP-1 at (145)Lys/Lys(146), resulting in a small (9-kDa) C-terminal peptide of IGFBP-1 in first trimester decidua (PMID:15070833)
• MMP-3 is specifically expressed in squamous cell carcinomas of the head and neck and its expression correlates with their invasion capacity. (PMID:15094779)
• MMP3 may have a role in response to chemotherapy in head and neck squamous cell carcinoma, as demonstrated by an analysis of its polymorphism (PMID:15102660)
• MMP3 5A/6A promoter polymorphism does not appear to influence breast cancer susceptibility but may be linked to a higher risk for metastasizing among breast cancer patients (PMID:15161710)
• Data suggest that proMMP-3 (prostromelysin 1) may play an essential role in degrading and remodeling the extracellular matrix in workers with pneumoconiosis, and that proMMP-3 may also reflect the stage of pneumoconiosis disease. (PMID:15203551)
• Recent large Japanese case-control studies identified connexin-37 (GJA-4), plasminogen activator inhibitor-1 (PAI-1), and stromelysin-1 (MMP-3) polymorphisms as risk factors for myocardial infarction. (PMID:15234427)
• The presence of the MMP1-2G and MMP3-6A alleles seemed to be associated with decreased risk of head and neck squamous cell carcinoma but mainly when they were carried by the same haplotype. (PMID:15274394)
• No general associations of MMP-1 and MMP-3 genes to primary sclerosing cholangitis(PSC) or ulcerative colitis(UC) among Norwegians, but specific alleles were associated to subsets of PSC patients with UC and cholangiocarcinoma. (PMID:15288468)
• CD154 induced production of TNF-alpha, IL-6, and MMP-3 in rheumatoid arthritis chondrocytes. (PMID:15290728)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp23bb	ENSDARG00000009825
danio_rerio	mmp25b	ENSDARG00000010556
danio_rerio	hpxa	ENSDARG00000012609
danio_rerio	mmp30	ENSDARG00000045887
danio_rerio	mmp25a	ENSDARG00000077290
danio_rerio	mmp13b	ENSDARG00000100794
mus_musculus	Mmp3	ENSMUSG00000043613
rattus_norvegicus	Mmp3	ENSRNOG00000032626
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), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Stromelysin-1 — P08254 (reviewed: P08254)

Alternative names: Matrix metalloproteinase-3, Transin-1

All UniProt accessions (3): P08254, E9PKX2, H7C139

UniProt curated annotations — full annotation on UniProt →

Function. Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates different molecules including growth factors, plasminogen or other matrix metalloproteinases such as MMP9. Once released into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin cascade signaling pathway. Also acts intracellularly. For example, in dopaminergic neurons, gets activated by the serine protease HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration by mediating microglial activation and alpha-synuclein/SNCA cleavage. In addition, plays a role in immune response and possesses antiviral activity against various viruses such as vesicular stomatitis virus, influenza A virus (H1N1) and human herpes virus 1. Mechanistically, translocates from the cytoplasm into the cell nucleus upon virus infection to influence NF-kappa-B activities.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Nucleus. Cytoplasm.

Post-translational modifications. Directly cleaved by HTRA2 to produce active form.

Disease relevance. Coronary heart disease 6 (CHDS6) [MIM:614466] A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. Disease susceptibility is associated with variants affecting the gene represented in this entry. A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.

Activity regulation. Enzymatic activity is activated by HTRA2 in dopaminergic cells upon mitochondrial stress.

Cofactor. Binds 4 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 (1): NP_002413* (*=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 3.4.24.17 — stromelysin 1 (BRENDA: 6 organisms, 110 substrates, 260 inhibitors, 9 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ARG-PRO-LYS-PRO-GLN-GLN-PHE-PHE-GLY-LEU-NORLEUCI	0.9–1.4	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-T	0.066	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-V	0.025	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LYS-PRO-GLN-G	0.05	1
2,4-DINITROPHENYL-PRO-TYR-ALA-TYR-TRP-MET-ARG-NH	0.1	1
ACETYL-PRO-LEU-GLY-THIOESTER-LEU-LEU-GLY-ETHYLES	0.27	1
ACETYL-PRO-LEU-GLY-[2-MERCAPTO-4-METHYL-PENTANOY	0.395	1
ACETYL-PRO-LEU-GLY-THIOESTER-LEU-LEU-GLY ETHYL E	—	0
ARG-PRO-LYS-PRO-GLN-GLN-PHE-PHE-GLY-LEU-NLE-NH2	—	0
BETA-CASEIN	—	0

UniProt features (64 total): binding site 24, strand 17, helix 8, repeat 4, signal peptide 1, propeptide 1, active site 1, chain 1, disulfide bond 1, sequence variant 1, sequence conflict 1, turn 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1HY7	X-RAY DIFFRACTION	1.5
1CIZ	X-RAY DIFFRACTION	1.64
1HFS	X-RAY DIFFRACTION	1.7
1CAQ	X-RAY DIFFRACTION	1.8
1USN	X-RAY DIFFRACTION	1.8
1C3I	X-RAY DIFFRACTION	1.83
4G9L	X-RAY DIFFRACTION	1.88
1G49	X-RAY DIFFRACTION	1.9
1SLM	X-RAY DIFFRACTION	1.9
4DPE	X-RAY DIFFRACTION	1.96
4JA1	X-RAY DIFFRACTION	1.96
1B8Y	X-RAY DIFFRACTION	2
1CQR	X-RAY DIFFRACTION	2
1D7X	X-RAY DIFFRACTION	2
1G4K	X-RAY DIFFRACTION	2
1QIA	X-RAY DIFFRACTION	2
1QIC	X-RAY DIFFRACTION	2
2D1O	X-RAY DIFFRACTION	2.02
2USN	X-RAY DIFFRACTION	2.2
1SLN	X-RAY DIFFRACTION	2.27
1B3D	X-RAY DIFFRACTION	2.3
1BQO	X-RAY DIFFRACTION	2.3
7S7L	X-RAY DIFFRACTION	2.34
3OHL	X-RAY DIFFRACTION	2.36
6MAV	X-RAY DIFFRACTION	2.37
1D8F	X-RAY DIFFRACTION	2.4
1D8M	X-RAY DIFFRACTION	2.44
1G05	X-RAY DIFFRACTION	2.45
1BIW	X-RAY DIFFRACTION	2.5
3OHO	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08254-F1	86.12	0.59

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): 219

Ligand- & substrate-binding residues (24): 92 (in inhibited form); 124; 158; 168; 170; 175; 176; 178; 180; 183; 190; 192 …

Disulfide bonds (1): 290–477

Function

Pathways and Gene Ontology

Reactome pathways

19 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-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-2179392	EGFR Transactivation by Gastrin
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-416476	G alpha (q) signalling events
R-HSA-449147	Signaling by Interleukins
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 238 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MODULE_172, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, chr11q22, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (18): proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), extracellular matrix organization (GO:0030198), regulation of cell migration (GO:0030334), collagen catabolic process (GO:0030574), positive regulation of protein-containing complex assembly (GO:0031334), cellular response to reactive oxygen species (GO:0034614), innate immune response (GO:0045087), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), cellular response to lipopolysaccharide (GO:0071222), cellular response to amino acid stimulus (GO:0071230), cellular response to UV-A (GO:0071492), cellular response to nitric oxide (GO:0071732), regulation of neuroinflammatory response (GO:0150077), response to amyloid-beta (GO:1904645), negative regulation of reactive oxygen species metabolic process (GO:2000378), immune system process (GO:0002376)

GO Molecular Function (9): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular matrix (GO:0031012), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	2
Signal Transduction	2
Collagen formation	1
Gastrin-CREB signalling pathway via PKC and MAPK	1
Signaling by Interleukins	1
ESR-mediated signaling	1
Immune System	1
Signaling by GPCR	1
GPCR downstream signalling	1
Cytokine Signaling in Immune system	1
G alpha (q) signalling events	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to oxygen-containing compound	3
cellular anatomical structure	3
protein metabolic process	2
peptidase activity	2
endopeptidase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
cell migration	1
regulation of cell motility	1
catabolic process	1
collagen metabolic process	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
immune response	1
defense response to symbiont	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
response to amino acid	1
cellular response to acid chemical	1
cellular response to UV	1
response to UV-A	1
response to nitric oxide	1
cellular response to reactive nitrogen species	1
regulation of inflammatory response	1
neuroinflammatory response	1
response to nitrogen compound	1
response to oxygen-containing compound	1

Protein interactions and networks

STRING

3098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP3	TIMP1	P01033	998
MMP3	SPP1	P10451	992
MMP3	TIMP2	P16035	959
MMP3	FN1	P02751	932
MMP3	IBSP	P21815	920
MMP3	ADAMTS5	Q9UNA0	883
MMP3	DMP1	Q13316	873
MMP3	TIMP4	Q99727	865
MMP3	ADAMTS3	O15072	864
MMP3	ELN	P15502	862
MMP3	SERPINE1	P05121	861
MMP3	ADAMTS4	O75173	859
MMP3	TIMP3	P35625	851
MMP3	TNF	P01375	846
MMP3	ACAN	P16112	843

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MEOX2	MMP3	psi-mi:“MI:0915”(physical association)	0.560
MMP3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MMP3	APOE	psi-mi:“MI:0914”(association)	0.530
MMP3	MMP10	psi-mi:“MI:0914”(association)	0.530
MMP3	TIMP1	psi-mi:“MI:0407”(direct interaction)	0.440
TIGD7	MMP3	psi-mi:“MI:0914”(association)	0.350
IFNG	MMP3	psi-mi:“MI:0914”(association)	0.350
MMP3	VGF	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): MMP3 (Two-hybrid), KIAA0319L (Affinity Capture-MS), MMP10 (Affinity Capture-MS), CLU (Affinity Capture-MS), PTPRS (Affinity Capture-MS), CLN5 (Affinity Capture-MS), HBD (Affinity Capture-MS), NUCB1 (Affinity Capture-MS), APOE (Affinity Capture-MS), TIMP3 (Affinity Capture-MS), MMP10 (Affinity Capture-MS), APOE (Affinity Capture-MS), PTPRS (Affinity Capture-MS), NUCB1 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS)

ESM2 similar proteins: F1RWC3, F7A4A7, O02668, O08523, O18733, O55123, O60494, O70244, O75443, O88923, P03957, P07152, P08253, P08254, P09238, P14780, P28862, P28863, P33434, P33436, P50757, P52176, P56677, P57999, P97435, P98072, P98073, P98074, P98092, Q0IIH7, Q29RU2, Q2PC93, Q3ZCN5, Q5ZQU0, Q62635, Q6V0K7, Q6ZRI0, Q70E20, Q8BG22, Q8R4U0

Diamond homologs: A4KX75, D0EM77, G5EBU3, O04529, O18733, O18767, O18927, O23507, O55123, O55761, O60882, O62806, O77656, P03956, P03957, P07152, P08253, P08254, P09237, P09238, P13943, P14780, P21692, P22757, P23097, P28862, P28863, P29136, P33434, P33435, P33436, P34960, P39900, P41245, P41246, P45452, P50280, P50281, P50282, P50757

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
ZMYND8	“down-regulates quantity by repression”	MMP3	“transcriptional regulation”
MMP3	“down-regulates quantity by destabilization”	ACAN	cleavage
MMP3	up-regulates	HBEGF	cleavage
TCF20	“up-regulates quantity by expression”	MMP3	“transcriptional regulation”
SRC	“up-regulates activity”	MMP3
MMP3	“up-regulates activity”	SPP1	cleavage
MMP3	“down-regulates quantity by destabilization”	HAPLN1	cleavage
MMP3	“down-regulates quantity by destabilization”	DCN	cleavage
MMP3	up-regulates	ECM_disassembly
MMP3	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	12
Benign	26

Top pathogenic / likely-pathogenic (0)

SpliceAI

1118 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102836225:CC:C	acceptor_gain	1.0000
11:102836226:CC:C	acceptor_gain	1.0000
11:102837292:TCTTA:T	donor_loss	1.0000
11:102837293:CTTA:C	donor_loss	1.0000
11:102837294:TTA:T	donor_loss	1.0000
11:102837295:T:TG	donor_loss	1.0000
11:102837296:A:AC	donor_gain	1.0000
11:102837296:A:C	donor_loss	1.0000
11:102837297:C:CC	donor_gain	1.0000
11:102837397:CAAAT:C	acceptor_gain	1.0000
11:102837398:AAAT:A	acceptor_gain	1.0000
11:102837399:AAT:A	acceptor_gain	1.0000
11:102837400:AT:A	acceptor_gain	1.0000
11:102837401:TC:T	acceptor_loss	1.0000
11:102837402:C:CC	acceptor_gain	1.0000
11:102837404:G:C	acceptor_gain	1.0000
11:102837408:C:CT	acceptor_gain	1.0000
11:102837409:A:T	acceptor_gain	1.0000
11:102838593:T:TA	donor_gain	1.0000
11:102838599:T:C	donor_gain	1.0000
11:102839105:ATTAC:A	donor_loss	1.0000
11:102839106:TTAC:T	donor_loss	1.0000
11:102839107:TAC:T	donor_loss	1.0000
11:102839108:A:AT	donor_loss	1.0000
11:102840133:C:A	donor_gain	1.0000
11:102840422:CACT:C	donor_loss	1.0000
11:102840423:ACTC:A	donor_loss	1.0000
11:102840424:CTCA:C	donor_loss	1.0000
11:102840425:TCA:T	donor_loss	1.0000
11:102840426:CACCA:C	donor_loss	1.0000

AlphaMissense

3149 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102842441:A:C	F163L	0.990
11:102842441:A:T	F163L	0.990
11:102842443:A:G	F163L	0.990
11:102842695:C:A	W109C	0.990
11:102842695:C:G	W109C	0.990
11:102842509:A:G	W141R	0.989
11:102842509:A:T	W141R	0.989
11:102838612:C:G	A390P	0.985
11:102839155:C:G	A342P	0.983
11:102842697:A:G	W109R	0.983
11:102842697:A:T	W109R	0.983
11:102840151:C:G	A298P	0.982
11:102842257:A:C	F174L	0.982
11:102842257:A:T	F174L	0.982
11:102842259:A:G	F174L	0.982
11:102842507:C:A	W141C	0.982
11:102842507:C:G	W141C	0.982
11:102842172:A:G	W203R	0.980
11:102842172:A:T	W203R	0.980
11:102842170:C:A	W203C	0.979
11:102842170:C:G	W203C	0.979
11:102840557:C:T	G221D	0.976
11:102840143:G:C	S300R	0.975
11:102840143:G:T	S300R	0.975
11:102840145:T:G	S300R	0.975
11:102840456:C:G	D255H	0.975
11:102837316:C:G	A439P	0.974
11:102840553:G:C	H222Q	0.974
11:102840553:G:T	H222Q	0.974
11:102840567:G:C	H218D	0.974

dbSNP variants (sampled 300 via entrez): RS1000987215 (11:102841438 C>G,T), RS1001019605 (11:102841066 A>G), RS1001827942 (11:102836325 T>C), RS1002989563 (11:102844211 C>G), RS1003020071 (11:102843890 A>G,T), RS1003357622 (11:102845371 C>T), RS1004913378 (11:102840669 A>G), RS1005282394 (11:102835902 A>G,T), RS1005315068 (11:102835549 A>C,G), RS1005485440 (11:102841991 T>C), RS1005564060 (11:102840309 T>C), RS1007311641 (11:102838775 A>G), RS1007494221 (11:102844600 G>A), RS1007694688 (11:102838929 C>G), RS1009335181 (11:102841450 G>T)

Disease associations

OMIM: gene MIM:185250 | disease phenotypes: MIM:614466

GenCC curated gene-disease

Mondo (1): coronary heart disease, susceptibility to, 6 (MONDO:0013765)

Orphanet (1): Orofacial clefting syndrome (Orphanet:139039)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001529_3	Alzheimer’s disease	1.000000e-06
GCST002665_4	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2.000000e-44
GCST003264_1314	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_1321	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_273	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_716	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003264_717	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003265_161	Post bronchodilator FEV1/FVC ratio in COPD	6.000000e-07
GCST003265_165	Post bronchodilator FEV1/FVC ratio in COPD	7.000000e-07
GCST003265_176	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_191	Post bronchodilator FEV1/FVC ratio in COPD	6.000000e-07
GCST003265_348	Post bronchodilator FEV1/FVC ratio in COPD	7.000000e-07
GCST006585_2534	Blood protein levels	2.000000e-33
GCST008474_13	Peripheral artery disease	4.000000e-09
GCST009731_48	Blood protein levels in cardiovascular risk	5.000000e-160

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004744	matrix metalloproteinase measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0004713	FEV/FVC ratio
EFO:0010608	stromelysin‐1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111321 (SELECTIVITY GROUP), CHEMBL283 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 282,741 (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
CHEMBL1356238	PYRITHIONE	4	15,582
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL50	QUERCETIN	3	74,559
CHEMBL75094	PRINOMASTAT	3	8,839
CHEMBL115653	CIPEMASTAT	2	359
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL206815	APRATASTAT	2	256
CHEMBL2107228	SOLIMASTAT	2	104
CHEMBL261932	TANOMASTAT	2	1,980
CHEMBL279786	BATIMASTAT	2	21,247
CHEMBL440498	CTS-1027	2	615
CHEMBL76222	REBIMASTAT	2	344

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs35068180	Efficacy	3	chlorthalidone;lisinopril	Hypertension
rs35068180	Efficacy	3	pravastatin	Coronary Artery Disease

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs35068180	MMP3	3	6.00	2	pravastatin;chlorthalidone;lisinopril

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
batimastat	Inhibition	9.19	pIC50
UK-356618	Inhibition	8.2	pIC50
CM-352	Inhibition	7.92	pIC50
CGS-27023A	Inhibition	7.8	pIC50
ilomastat	Inhibition	7.49	pIC50
marimastat	Inhibition	6.64	pIC50

Binding affinities (BindingDB)

197 measured of 283 human assays (283 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
piperidinyl glycine derivative, 24f	KI	0.19 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
Trocade	KI	0.53 nM
4-({[4-(3,4-Dimethylphenoxy)phenyl]sulfonyl}methyl)-N-hydroxy-1-prop-2-ynylpiperidine-4-carboxamide Hydrochloride	KI	0.9 nM
(2R)-N-hydroxy-3-methyl-2-[(4-phenoxybenzene)sulfonamido]butanamide	IC50	1 nM
N-hydroxy-1-methanesulfonyl-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	2 nM
N-hydroxy-4-{[(4-phenoxybenzene)sulfonyl]methyl}piperidine-4-carboxamide hydrochloride	KI	2.8 nM
(2R)-2-{[4-(4-bromophenyl)benzene]sulfonamido}-N-hydroxy-3-methylbutanamide	IC50	3 nM
(2S)-2-{[4-(4-bromophenyl)benzene]sulfonamido}-3-methylbutanoic acid	IC50	4 nM
(R)-[1-(4-Methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonic Acid	KI	5 nM
(2R)-2-{[4-(4-bromophenyl)benzene]sulfonamido}-3-methylbutanoic acid	IC50	5 nM
(4S)-5-[3-(carboxymethyl)piperidin-1-yl]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	12 nM	US-8691753
2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxypropanamide	KI	15 nM
CGS 27023A Analog 22	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
CGS 27023	KI	20 nM
(2S)-N-hydroxy-3-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylamino]-2-(4-methylsulfonylpiperazin-1-yl)propanamide	IC50	21 nM	US-8633196: Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	23 nM
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4,4-dimethylpentanamide	KI	28 nM
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-3-phenylpropanamide	KI	29 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
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-(methylsulfanyl)butanamide	KI	31 nM
(2S)-N-hydroxy-3-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylamino]-2-(4-propan-2-ylsulfonylpiperazin-1-yl)propanamide	IC50	33 nM	US-8633196: Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	34 nM
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxypropanamide	KI	36 nM
2-[(2-cyclohexylethyl)(4-methoxybenzene)sulfonamido]-N-hydroxyacetamide	KI	38 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
(2R,3S)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-3-methylpentanamide	KI	39 nM
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]pentanoic acid	KI	39.3 nM	US-8691753
(2S)-2-(4-ethylpiperazin-1-yl)-N-hydroxy-3-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylamino]propanamide	IC50	41 nM	US-8633196: Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics
(2R)-N-hydroxy-2-[(4-methoxybenzene)(pyridin-3-ylmethyl)sulfonamido]-4,4-dimethylpentanamide	KI	42 nM
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-3-cyclohexyl-N-hydroxypropanamide	KI	44 nM
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	45 nM	US-8691753
(2R)-N-hydroxy-2-[(4-methoxybenzene)(pyridin-3-ylmethyl)sulfonamido]-4-methylpentanamide	KI	46 nM
Inhibitor, 18	KI	47 nM
(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-3-(tert-butoxy)-N-hydroxypropanamide	KI	48 nM
(4S)-5-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	49 nM	US-8691753
2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-(morpholin-4-yl)butanamide	KI	50 nM

ChEMBL bioactivities

2188 potent at pChembl≥5 of 2422 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	PRINOMASTAT
10.42	IC50	0.038	nM	CHEMBL330028
9.72	IC50	0.191	nM	ILOMASTAT
9.70	IC50	0.2	nM	CHEMBL1801056
9.64	IC50	0.23	nM	PRINOMASTAT
9.57	Ki	0.27	nM	PRINOMASTAT
9.52	IC50	0.3	nM	CTS-1027
9.52	IC50	0.3	nM	CHEMBL400083
9.52	IC50	0.3	nM	CHEMBL473539
9.46	Ki	0.35	nM	CHEMBL56837
9.44	Ki	0.36	nM	CHEMBL168150
9.40	IC50	0.4	nM	CHEMBL251918
9.37	Ki	0.43	nM	CHEMBL291264
9.30	Ki	0.5	nM	CHEMBL425316
9.30	IC50	0.5	nM	CHEMBL154044
9.30	IC50	0.5012	nM	CHEMBL154044
9.29	Ki	0.51	nM	CHEMBL61193
9.28	Ki	0.53	nM	CHEMBL355797
9.25	IC50	0.56	nM	BATIMASTAT
9.22	IC50	0.6	nM	CHEMBL279078
9.19	IC50	0.65	nM	BATIMASTAT
9.15	IC50	0.7	nM	CHEMBL104022
9.15	IC50	0.7	nM	CHEMBL140970
9.15	IC50	0.7	nM	CHEMBL4088630
9.15	IC50	0.7079	nM	CHEMBL140970
9.15	IC50	0.7	nM	CHEMBL320402
9.15	IC50	0.7	nM	CHEMBL296911
9.15	IC50	0.7	nM	CHEMBL342172
9.15	IC50	0.7	nM	CHEMBL141080
9.14	IC50	0.73	nM	BATIMASTAT
9.12	IC50	0.75	nM	BATIMASTAT
9.10	Ki	0.8	nM	CHEMBL76158
9.10	Ki	0.8	nM	CHEMBL93395
9.10	IC50	0.8	nM	CHEMBL288896
9.05	Ki	0.9	nM	CHEMBL72511
9.05	IC50	0.9	nM	CHEMBL102438
9.02	Ki	0.96	nM	CHEMBL308533
9.02	Ki	0.96	nM	CHEMBL92828
9.00	IC50	1	nM	CHEMBL252117
9.00	IC50	1	nM	CHEMBL251917
9.00	IC50	1	nM	CHEMBL398641
9.00	IC50	1	nM	CHEMBL149977
9.00	IC50	1	nM	CHEMBL337594
8.96	IC50	1.1	nM	CHEMBL317508
8.96	IC50	1.1	nM	PRINOMASTAT
8.96	IC50	1.1	nM	CHEMBL344633
8.96	IC50	1.1	nM	CHEMBL105311
8.92	IC50	1.2	nM	CHEMBL125901
8.92	IC50	1.2	nM	CHEMBL321180
8.92	IC50	1.2	nM	CHEMBL111798

PubChem BioAssay actives

1979 with measured affinity, of 3100 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
3-methyl-2-[(4-phenylphenyl)sulfonylamino]butanoic acid	732014: Inhibition of MMP3 (unknown origin)	ic50	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	1929084: Inhibition of MMP-3 (unknown origin)	ki	<0.0001	uM
2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid	732014: Inhibition of MMP3 (unknown origin)	ic50	<0.0001	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107503: Inhibition of human matrix metalloprotease-3	ic50	0.0002	uM
N-hydroxy-4-[4-(4-methoxyphenoxy)phenyl]sulfonyl-1-prop-2-ynylpiperidine-4-carboxamide	604450: Inhibition of human MMP3 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM
N-hydroxy-1-(2-methoxyethyl)-4-(4-phenoxyphenyl)sulfonylpiperidine-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	0.0003	uM
1-cyclopropyl-N-hydroxy-4-(4-phenoxyphenyl)sulfonylpiperidine-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	0.0003	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162786: Inhibition of human recombinant MMP3 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0003	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-phenoxyphenyl)sulfonylthiomorpholine-3-carboxamide	1863876: Inhibition of MMP-3 (unknown origin)	ic50	0.0003	uM
(2R,3R,4R,5R)-N,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide	107528: Inhibition of human recombinant matrix metalloprotease 3	ki	0.0003	uM
N-hydroxy-2-methyl-2-[4-[3-methyl-4-[3-[2-(methylamino)ethoxy]phenyl]phenyl]piperidin-1-yl]sulfonylpropanamide	311965: Inhibition of MMP3	ic50	0.0003	uM
(2R,3R,4R,5R)-1-(4-but-2-ynoxyphenyl)sulfonyl-N,4,5-trihydroxy-3-methoxypiperidine-2-carboxamide	107660: Inhibition of recombinant human matrix metalloprotease-3	ki	0.0004	uM
2-[4-[4-[3-(2-aminoethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-N-hydroxy-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0004	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-[3-(3-methyl-4-phenylphenyl)propyl]butanediamide	107362: Concentration required to inhibit the catalytic domain Matrix metalloprotease-3 using Nagase fluorogenic as a substrate.	ic50	0.0005	uM
2-[ethoxy-(4-phenoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	107530: Inhibitory activity against matrix metalloprotease-3 (MMP-3)(stromelysin-1).	ki	0.0005	uM
2-[[4-(4-aminophenoxy)phenyl]-ethoxyphosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	107530: Inhibitory activity against matrix metalloprotease-3 (MMP-3)(stromelysin-1).	ki	0.0005	uM
(2R,3R,4R,5S)-N,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide	107528: Inhibition of human recombinant matrix metalloprotease 3	ki	0.0005	uM
(2S,3R)-N-hydroxy-2-methyl-N’-[(2S)-1-(methylamino)-1-oxo-3-(5,6,7,8-tetrahydronaphthalen-1-yl)propan-2-yl]-3-(2-methylpropyl)butanediamide	107358: Activity against Matrix metalloprotease-3 (MMP-3).	ic50	0.0006	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide	107358: Activity against Matrix metalloprotease-3 (MMP-3).	ic50	0.0006	uM
(3S)-N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2,2-dimethylthiomorpholine-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0007	uM
(6S)-N-hydroxy-7-(4-methoxyphenyl)sulfonyl-5,5-dimethyl-1,4,7-oxathiazonane-6-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0007	uM
4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	107491: In vitro inhibitory activity against matrix metalloprotease-3	ic50	0.0007	uM
N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2,2-dimethylthiomorpholine-3-carboxamide	1454755: Inhibition of truncated human recombinant MMP3 catalytic domain expressed in Escherichia coli BL21(DE3) after 3 hrs in presence of [H]-transferrin	ic50	0.0007	uM
(2S)-4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	104747: Inhibition of matrix metalloprotease-3	ic50	0.0007	uM
(2R)-4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	107512: Inhibition of matrix metalloprotease-3	ic50	0.0007	uM
(3S)-N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2,2-dimethyl-1,4-thiazepane-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0007	uM
3-[3-[[(2S)-2-[[(2R)-5-(4-chlorophenyl)-2-[2-(hydroxyamino)-2-oxoethyl]pentanoyl]amino]-3-cyclohexylpropanoyl]amino]propanoylamino]propanoic acid	107656: Inhibitory constant against matrix metalloprotease-3	ki	0.0008	uM
4-benzylsulfanyl-N-hydroxy-2-[[2-[(4-methoxyphenyl)methylamino]-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]butanamide	107491: In vitro inhibitory activity against matrix metalloprotease-3	ic50	0.0009	uM
(2S,3R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-3-(hydroxymethyl)-2-(4-methoxyphenyl)butanediamide	107685: Inhibitory potency against Matrix metalloprotease-3 (MMP-3)	ki	0.0009	uM
(2R,4Z)-1-[4-(4-fluorophenoxy)phenyl]sulfonyl-N-hydroxy-4-methoxyiminopyrrolidine-2-carboxamide	107492: In vitro inhibition activity of human recombinant stromelysin (Matrix metalloprotease-3)	ic50	0.0010	uM
(2R,4Z)-1-(4-butoxyphenyl)sulfonyl-N-hydroxy-4-methoxyiminopyrrolidine-2-carboxamide	107492: In vitro inhibition activity of human recombinant stromelysin (Matrix metalloprotease-3)	ic50	0.0010	uM
tert-butyl (6S,9R,10S)-10-(hydroxycarbamoyl)-6-(methylcarbamoyl)-9-(2-methylpropyl)-8-oxo-1,7-diazacyclotridecane-1-carboxylate	107532: Inhibition of matrix metalloprotease-3 (MMP-3).	ki	0.0010	uM
(2R,4Z)-1-[4-(4-fluorophenoxy)phenyl]sulfonyl-N-hydroxy-4-[(2-methylpropan-2-yl)oxyimino]pyrrolidine-2-carboxamide	107492: In vitro inhibition activity of human recombinant stromelysin (Matrix metalloprotease-3)	ic50	0.0010	uM
methyl 3-[3-[[(2S)-2-[[(2R)-5-(4-chlorophenyl)-2-[2-(hydroxyamino)-2-oxoethyl]pentanoyl]amino]-3-cyclohexylpropanoyl]amino]propanoylamino]propanoate	107656: Inhibitory constant against matrix metalloprotease-3	ki	0.0010	uM
(3S)-N-hydroxy-6-(methoxymethoxy)-4-(4-methoxyphenyl)sulfonyl-2,2-dimethyl-1,4-thiazepane-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0010	uM
N-hydroxy-2-[4-[4-[3-(2-hydroxyethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0010	uM
2-[4-[4-[3-[2-(dimethylamino)ethoxy]phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-N-hydroxy-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0010	uM
N-hydroxy-2-[4-[4-[6-(2-hydroxyethoxy)-2-pyridinyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide	311965: Inhibition of MMP3	ic50	0.0010	uM
4-benzylsulfanyl-2-[[2-(dipyridin-2-ylmethylamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-hydroxybutanamide	107491: In vitro inhibitory activity against matrix metalloprotease-3	ic50	0.0011	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(5-pyridin-2-ylthiophen-2-yl)sulfonyl-1,4-thiazepane-3-carboxamide	107361: In vitro inhibitory activity against matrix metalloprotease-3.	ic50	0.0011	uM
2-[[4-(4-cyanophenyl)phenoxy]methyl]-N-hydroxy-4-(4-oxo-1,2,3-benzotriazin-3-yl)butanamide	107502: Inhibition of Matrix metalloprotease-3	ic50	0.0011	uM
(2S,3R)-N,2-dihydroxy-N’-[(2S)-1-(1H-indol-3-yl)-3,3-dimethyl-1-oxobutan-2-yl]-3-(2-methylpropyl)butanediamide	104927: In vitro inhibitory activity against human recombinant matrix metalloprotease 3	ic50	0.0012	uM
(1R,2R,5S)-2-[(4-oxo-1,2,3-benzotriazin-3-yl)methyl]-5-(4-pyridin-4-ylphenyl)sulfanylcyclopentane-1-carboxylic acid	107514: Inhibitory activity against matrix metalloprotease-3 (MMP3)	ic50	0.0012	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(1H-indol-3-yl)-3,3-dimethyl-1-oxobutan-2-yl]-3-(2-methylpropyl)-2-prop-2-enylbutanediamide	104927: In vitro inhibitory activity against human recombinant matrix metalloprotease 3	ic50	0.0012	uM
(4R)-1-tert-butyl-N-hydroxy-3-(4-methoxyphenyl)sulfonyl-6-oxo-1,3-diazinane-4-carboxamide	107360: Inhibition of Matrix metalloprotease-3	ic50	0.0013	uM
[(2S)-2-[[(2R)-1-anilino-4-methyl-1-oxopentan-2-yl]carbamoyl]-4-phenylbutyl]-[4-(1,3-dioxoisoindol-2-yl)butyl]phosphinic acid	104899: Inhibition of recombinant matrix metalloprotease-3 (MMP-3)	ki	0.0014	uM
(2R)-2-[3-(4-chlorophenyl)propyl]-N-[(2S)-3-cyclohexyl-1-[[3-[(3-morpholin-4-yl-3-oxopropyl)amino]-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxybutanediamide	107656: Inhibitory constant against matrix metalloprotease-3	ki	0.0014	uM
(7S,8R,11S)-7-N-hydroxy-11-N-methyl-9-oxo-8-[2-(4-propylphenyl)ethyl]-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104742: Inhibition of fibroblast stromelysin (MMP-3)	ic50	0.0015	uM
N-hydroxy-4-[(4-phenoxyphenyl)sulfonylmethyl]-1-prop-2-ynylpiperidine-4-carboxamide	313839: Inhibition of MMP3	ic50	0.0015	uM
N-[[3-[4-[[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]phenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328777: Inhibition of recombinant human AMPA-activated MMP3 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases secretion, increases expression	9
Glucosamine	increases expression, increases secretion, decreases expression, affects cotreatment, decreases secretion (+2 more)	7
sodium arsenite	decreases reaction, increases expression, affects cotreatment, decreases expression	6
Estradiol	affects cotreatment, decreases secretion, decreases reaction, increases expression, decreases expression (+1 more)	5
Lipopolysaccharides	decreases reaction, increases expression, increases reaction, affects response to substance	5
Progesterone	affects cotreatment, decreases secretion, increases expression, decreases expression, decreases reaction	5
Particulate Matter	decreases reaction, increases expression, decreases expression	5
pyrazolanthrone	increases expression, decreases reaction	4
Resveratrol	decreases reaction, increases secretion, increases expression, increases activity	4
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression, increases methylation	4
Endosulfan	affects expression, increases expression	4
Tetrachlorodibenzodioxin	decreases reaction, increases expression, decreases secretion	4
Tetradecanoylphorbol Acetate	increases expression, increases reaction, decreases reaction	4
Bleomycin	decreases reaction, increases expression	3
Copper	affects cotreatment, increases activity, increases expression, affects binding, decreases expression	3
Dexamethasone	increases secretion, decreases reaction, increases expression, decreases expression	3
Hydrogen Peroxide	decreases expression, increases expression, decreases reaction, affects reaction	3
Nicotine	increases reaction, affects reaction, increases expression	3
Quercetin	increases expression, increases reaction, decreases expression, decreases reaction	3
Aflatoxin B1	affects expression, increases expression	3
cobaltiprotoporphyrin	decreases reaction, increases expression, increases reaction	2
2-methyl-4-isothiazolin-3-one	increases expression, increases secretion	2
hydroquinone	affects expression, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases secretion	2
2,2’,4,6,6’-pentachlorobiphenyl	increases expression, decreases reaction	2
Acetylcysteine	increases secretion, increases reaction, decreases reaction, increases expression	2
Calcitriol	increases expression	2
Cisplatin	affects cotreatment, increases expression, affects response to substance	2
Curcumin	increases expression	2
Folic Acid	affects expression, increases secretion	2

ChEMBL screening assays

448 unique, capped per target: 439 binding, 7 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL709182	Binding	Selectivity ratio for Matrix metalloprotease-2 over Matrix metalloprotease-3 (IC50)	MMPs inhibitors: new succinylhydroxamates with selective inhibition of MMP-2 over MMP-3. — Bioorg Med Chem Lett
CHEMBL827459	Functional	Ratio of IC50 value for MMP2 and MMP-3	N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP. — Bioorg Med Chem Lett
CHEMBL4000931	ADMET	Inhibition of APMA-activated recombinant human MMP-3 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	Discovery of Novel, Highly Potent, and Selective Matrix Metalloproteinase (MMP)-13 Inhibitors with a 1,2,4-Triazol-3-yl Moiety as a Zinc Binding Group Using a Structure-Based Design Approach. — J Med Chem

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AB53	BHK-MMP3	Spontaneously immortalized cell line	Male
CVCL_C7D9	Abcam A-549 MMP3 KO	Cancer cell line	Male
CVCL_C7DZ	Abcam HCT 116 MMP3 KO	Cancer cell line	Male
CVCL_C7EL	Abcam THP-1 MMP3 KO	Cancer cell line	Male
CVCL_D1TK	Abcam U-87MG MMP3 KO	Cancer cell line	Male
CVCL_D9KI	Ubigene HEK293 MMP3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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