MMP9

Summary

MMP9 (matrix metallopeptidase 9, HGNC:7176) is a protein-coding gene on chromosome 20q13.12, encoding Matrix metalloproteinase-9 (P14780). Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. In precision oncology, MMP9 SERUM LEVELS is associated with resistance to Bevacizumab in Inflammatory Breast Carcinoma (CIViC Level B).

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. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling.

Source: NCBI Gene 4318 — RefSeq curated summary.

At a glance

• Gene–disease (curated): metaphyseal anadysplasia 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 466 total — 2 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 26 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_004994

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7176
Approved symbol	MMP9
Name	matrix metallopeptidase 9
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100985
Ensembl biotype	protein_coding
OMIM	120361
Entrez	4318

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000372330, ENST00000898203, ENST00000898204

RefSeq mRNA: 1 — MANE Select: NM_004994 NM_004994

CCDS: CCDS13390

Canonical transcript exons

ENST00000372330 — 13 exons

Exon	Start	End
ENSE00000662462	46009866	46010098
ENSE00000845116	46010483	46010631
ENSE00000845117	46010922	46011050
ENSE00000845118	46011143	46011316
ENSE00000845119	46011574	46011747
ENSE00000845120	46012137	46012313
ENSE00000845121	46012427	46012582
ENSE00000845122	46013255	46013534
ENSE00000845123	46013657	46013796
ENSE00000845124	46014124	46014274
ENSE00000845125	46014371	46014474
ENSE00001457551	46016250	46016561
ENSE00001457585	46008908	46009064

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 99.85.

FANTOM5 (CAGE): breadth broad, TPM avg 463.3938 / max 19581.8008, expressed in 739 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184989	457.6311	714
184988	1.3704	170
185027	1.1004	121
185029	0.8792	113
185028	0.6995	101
185019	0.3515	101
185018	0.3258	94
185022	0.2531	92
185038	0.1414	60
185021	0.1249	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.85	gold quality
trabecular bone tissue	UBERON:0002483	99.62	gold quality
tibia	UBERON:0000979	99.52	gold quality
bone marrow	UBERON:0002371	98.03	gold quality
bone marrow cell	CL:0002092	96.75	gold quality
vermiform appendix	UBERON:0001154	95.86	gold quality
blood	UBERON:0000178	95.38	gold quality
cartilage tissue	UBERON:0002418	95.15	gold quality
skin of hip	UBERON:0001554	95.06	gold quality
lymph node	UBERON:0000029	93.49	gold quality
spleen	UBERON:0002106	92.96	gold quality
ileal mucosa	UBERON:0000331	92.39	gold quality
caecum	UBERON:0001153	89.91	gold quality
epithelium of nasopharynx	UBERON:0001951	89.23	gold quality
amniotic fluid	UBERON:0000173	88.37	gold quality
granulocyte	CL:0000094	88.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.95	gold quality
superficial temporal artery	UBERON:0001614	85.42	gold quality
thymus	UBERON:0002370	83.64	gold quality
right lung	UBERON:0002167	83.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.34	gold quality
upper lobe of left lung	UBERON:0008952	79.81	gold quality
upper lobe of lung	UBERON:0008948	78.96	gold quality
leukocyte	CL:0000738	78.40	gold quality
mononuclear cell	CL:0000842	77.54	gold quality
monocyte	CL:0000576	77.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.83	gold quality
pleura	UBERON:0000977	74.56	gold quality
connective tissue	UBERON:0002384	74.28	gold quality
adipose tissue	UBERON:0001013	74.25	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	14998.32
E-CURD-112	yes	14889.75
E-MTAB-8322	yes	14824.25
E-MTAB-7381	yes	4392.12
E-MTAB-8207	yes	1932.71
E-ANND-5	yes	779.76
E-MTAB-8142	yes	83.17
E-ANND-3	yes	17.50
E-MTAB-9801	yes	8.19
E-MTAB-7249	no	38.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ATF2, ATF3, BARX2, BMPR1A, CIITA, CITED2, CREB1, CREB3, CRKL, CTNNB1, DDRGK1, DLX3, EGR1, ELF3, ELF4, ELK1, EP300, ERG, ESR1, ETS1, ETS2, ETV4, ETV7, FOS, FOSL1, FOXC1, FOXM1, FOXN1, FOXO3, FOXO4, FOXP3, GSK3B, HDAC1, HIF1A, HMGA1, HOXB2, ID1

miRNA regulators (miRDB)

5 targeting MMP9, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6734-3P	99.15	66.27	1627

Literature-anchored findings (GeneRIF, showing 40)

• involvement of MMPs in microinvasive carcinomas (PMID:11168762)
• 125-kDa urinary gelatinase as being a complex of MMP-9 and NGAL and provides evidence that NGAL modulates MMP-9 activity by protecting it from degradation. (PMID:11486009)
• secretion in primary human monocytes induced by chemokines (PMID:11688724)
• Significant association with poor survival by MMP-9. (PMID:11742492)
• results indicate that two kinds of pro-form and active-form matrix metalloproteinases, MMP-2 and MMP-9, and their degradation products, are present in human seminal plasma (PMID:11756567)
• Multiple signaling pathways involved in activation of matrix metalloproteinase-9 in breast cancer cells (PMID:11781819)
• The CC chemokines CCL2 (MCP-1), CCL3 (MIP-1alpha), and CCL5 (RANTES) stimulated the release of monocyte MMP-9 protein in a bell-shaped dose-dependent manner. (PMID:11813159)
• Exposure of cryptic domains in the alpha 1-chain of laminin-1 by elastase stimulates macrophages urokinase and matrix metalloproteinase-9 expression. (PMID:11827968)
• overexpression of MMP-9 in HTLV-I- infected cells may be in part responsible for the invasiveness of adult T-cell leukemia cells. (PMID:11830485)
• in differentiating trophoblasts Nitric Oxide regulates the induction of MMP-2 and MMP-9 required for invasion during embryo (PMID:11833938)
• shed as membrane vesicle associated components by endothelial cells and this may be a mechanism for regulating focalized proteolytic activity vital to invasive and morphogenic events during angiogenesis (PMID:11839588)
• gelatinolytic activity in situ, in tissue sections of term placenta, is co-localized with gelatinase B (PMID:11839746)
• in pancreatic cancer, invasion into large veins and destroyed type veins could be a risk factor for liver metastasis and that increased expression MMP-2 and MMP-9 were related to such invasion. (PMID:11854622)
• MMP-9 activity is significantly elevated in SLE patients and correlated with disease activity in males but not females. These results suggest that MMP-9 plays a role in the pathogenesis of SLE. (PMID:11876767)
• Respiratory syncytial virus infection of HEp-2 cells induces matrix metalloproteinase-9 expression (PMID:11890521)
• C/C homozygosity at the C-1562T polymorphism of the promoter may be protective against coronary artery disease in Koreans. (PMID:11916008)
• increasing expression and endometrial carcinoma appear closely related (PMID:11920503)
• significantly increased activity seen in plasma of head and neck squamous cell carcinoma patients (PMID:11920505)
• activity significantly higher in lung cancer cells than uninvolved lung parenchyma; may be involved in tumor progression (PMID:11935310)
• The expression of MMP-9 was significantly increased in mesangial proliferative glomeruli and interstitial vascular walls of IgA nephropathy patients. (PMID:11940298)
• expression of MMP-9 in cervical cancer (PMID:11956628)
• The plasma MMP-9 levels in patients with HCC were significantly higher than those in the normal controls (PMID:11958288)
• Results suggest that gastrin increases MMP-9 expression, which is associated with increased invasion, and this is a putative mechanism regulating remodelling of the gastric epithelium. (PMID:11971760)
• Production of matrix metalloproteinase-9 in early stage B-CLL is suppressed by interferons alpha and gamma. (PMID:11986939)
• We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). (PMID:11994547)
• REVIEW: Role of gelatinase B in leukocytosis and stem cell mobilization. (PMID:11999552)
• novel regulation for the proteolytic activation of MMP-9 in human tissue (tissue-associated chymotrypsin-like proteinase, pM9A). (PMID:12004062)
• Overexpression of MMP-2 and MMP-9 in squamous cell carcinomas of immunosuppressed patients. (PMID:12029498)
• destruction of the surrounding matrix by endometriosis might be caused by various MMPs, which are mainly produced in stromal cells. (PMID:12034345)
• ox-LDL and HDL lipoproteins regulate the production by activated monocytes (PMID:12050187)
• Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor (PMID:12051944)
• FGF-2 and TPA induce matrix metalloproteinase-9 secretion in MCF-7 cells through PKC activation of the Ras/ERK pathway. (PMID:12054499)
• signalling pathways involved in MMP-9 regulation at the maternal-fetal interface (PMID:12062817)
• roughly constitutive TIMP-1 expression opposed to an inducible MMP-9 synthesis in Epstein–Barr virus-immortalized B lymphocytes (PMID:12063180)
• The X-ray crystal structure of the proform of human matrix metalloproteinase MMP9 has been solved to 2.5 A resolution (PMID:12077439)
• evaluation of the effect of increased levels of active MMP-9 in the central nervous system (PMID:12081477)
• Expression of MMP9 is elevated during PBSC mobilization by G-CSF. (PMID:12084167)
• Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B (PMID:12105194)
• structural basis of the adaptive molecular recognition by MMP9 (PMID:12126625)
• No allelic associations have been found between multiple sclerosis and the CA microsatellite marker in the promoter region of the gelatinase B gene in Belgian study populations. (PMID:12127674)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp9	ENSDARG00000042816
mus_musculus	Mmp9	ENSMUSG00000017737
rattus_norvegicus	Mmp9	ENSRNOG00000017539
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-9 — P14780 (reviewed: P14780)

Alternative names: 92 kDa gelatinase, 92 kDa type IV collagenase, Gelatinase B

All UniProt accessions (1): P14780

UniProt curated annotations — full annotation on UniProt →

Function. Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves NINJ1 to generate the Secreted ninjurin-1 form. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.

Subunit / interactions. Exists as monomer or homodimer; disulfide-linked. Also exists as heterodimer with LCN2. Macrophages and transformed cell lines produce only the monomeric form. Interacts with ECM1. (Microbial infection) Interacts with Staphylococcus aureus protein SSL5; this interaction inhibits MMP9 activity.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in neutrophils (at protein level). Produced by normal alveolar macrophages and granulocytes.

Post-translational modifications. Processing of the precursor yields different active forms of 64, 67 and 82 kDa. Sequentially processing by MMP3 yields the 82 kDa matrix metalloproteinase-9. N- and O-glycosylated.

Disease relevance. Intervertebral disc disease (IDD) [MIM:603932] A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. Disease susceptibility is associated with variants affecting the gene represented in this entry. Metaphyseal anadysplasia 2 (MANDP2) [MIM:613073] A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by histatin-3 1/24 (histatin-5). Inhibited by ECM1.

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

Induction. Activated by 4-aminophenylmercuric acetate and phorbol ester. Up-regulated by ARHGEF4, SPATA13 and APC via the JNK signaling pathway in colorectal tumor cells. (Microbial infection) Expression induced by M.bovis MPB83 (at protein level).

Miscellaneous. In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_004985* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000562	FN_type2_dom	Domain
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR006026	Peptidase_Metallo	Domain
IPR013806	Kringle-like	Homologous_superfamily
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
IPR036943	FN_type2_sf	Homologous_superfamily

Pfam: PF00040, PF00045, PF00413

Enzyme classification (BRENDA):

• EC 3.4.24.35 — gelatinase B (BRENDA: 11 organisms, 258 substrates, 185 inhibitors, 17 Km, 18 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-3-(2,4-DINITROPHENYL)-L-2,3-DIAMINOPROPIONYL-7	0.0042–0.005	2
STROMELYSIN1	—	2
65000 MW FORM OF VITRONECTIN	0.0015	1
SGFGSRYLTA	0.8	1
SGKGPRQITA	3.7	1
SGKIPRRLTA	1.4	1
SGKIPRTATA	4.7	1
SGKIPRTLTA	1.3	1
SGLKALMITA	2.4	1
SGLRPAKSTA	13.5	1
SGPLFYSVTA	0.5	1
SGPRAVSTTA	2.9	1
SGQPHYLTTA	1	1
VITRONECTIN	0.0013	1
(7-METHOXYCOUMARYL-4YL)ACETYLPLGLA2PR(2,4-DINITR	—	0

UniProt features (131 total): strand 48, binding site 21, helix 16, sequence variant 9, disulfide bond 7, turn 6, repeat 4, glycosylation site 3, domain 3, propeptide 2, compositionally biased region 2, chain 2, site 2, signal peptide 1, region of interest 1, short sequence motif 1, active site 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
6ESM	X-RAY DIFFRACTION	1.1
4XCT	X-RAY DIFFRACTION	1.3
8K5Y	X-RAY DIFFRACTION	1.52
4H1Q	X-RAY DIFFRACTION	1.59
5I12	X-RAY DIFFRACTION	1.59
5UE3	X-RAY DIFFRACTION	1.6
4WZV	X-RAY DIFFRACTION	1.65
4JIJ	X-RAY DIFFRACTION	1.7
5TH6	X-RAY DIFFRACTION	1.7
8K5V	X-RAY DIFFRACTION	1.7
4H3X	X-RAY DIFFRACTION	1.76
5UE4	X-RAY DIFFRACTION	1.8
5CUH	X-RAY DIFFRACTION	1.83
4JQG	X-RAY DIFFRACTION	1.85
4H82	X-RAY DIFFRACTION	1.9
8K5X	X-RAY DIFFRACTION	1.9
4HMA	X-RAY DIFFRACTION	1.94
1ITV	X-RAY DIFFRACTION	1.95
2OVX	X-RAY DIFFRACTION	2
2OVZ	X-RAY DIFFRACTION	2
2OW0	X-RAY DIFFRACTION	2
8K5W	X-RAY DIFFRACTION	2
1GKD	X-RAY DIFFRACTION	2.1
2OW1	X-RAY DIFFRACTION	2.2
1GKC	X-RAY DIFFRACTION	2.3
1L6J	X-RAY DIFFRACTION	2.5
2OW2	X-RAY DIFFRACTION	2.9
4H2E	X-RAY DIFFRACTION	2.9
5TH9	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14780-F1	82.96	0.52

Antibody-complex structures (SAbDab): 1 — 5TH9

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 402; 59–60 (cleavage; by mmp3); 106–107 (cleavage; by mmp3)

Ligand- & substrate-binding residues (21): 99 (in inhibited form); 131; 165; 175; 177; 182; 183; 185; 187; 190; 197; 199 …

Disulfide bonds (7): 230–256, 244–271, 288–314, 302–329, 347–373, 361–388, 516–704

Glycosylation sites (3): 38, 120, 127

Mutagenesis-validated functional residues (1):

Position	Phenotype
402	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-1433557	Signaling by SCF-KIT
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-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-1266738	Developmental Biology
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-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-422475	Axon guidance
R-HSA-449147	Signaling by Interleukins
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9675108	Nervous system development

MSigDB gene sets: 573 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, MODULE_172, VERHAAK_AML_WITH_NPM1_MUTATED_DN, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (27): skeletal system development (GO:0001501), positive regulation of protein phosphorylation (GO:0001934), proteolysis (GO:0006508), apoptotic process (GO:0006915), embryo implantation (GO:0007566), cell migration (GO:0016477), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), macrophage differentiation (GO:0030225), collagen catabolic process (GO:0030574), endodermal cell differentiation (GO:0035987), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA binding (GO:0043388), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), ephrin receptor signaling pathway (GO:0048013), positive regulation of keratinocyte migration (GO:0051549), cellular response to lipopolysaccharide (GO:0071222), cellular response to UV-A (GO:0071492), positive regulation of release of cytochrome c from mitochondria (GO:0090200), regulation of neuroinflammatory response (GO:0150077), negative regulation of cation transmembrane transport (GO:1904063), response to amyloid-beta (GO:1904645), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), negative regulation of epithelial cell differentiation involved in kidney development (GO:2000697), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243), regulation of multicellular organismal process (GO:0051239)

GO Molecular Function (11): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), collagen binding (GO:0005518), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	2
Immune System	2
Signaling by Receptor Tyrosine Kinases	1
Collagen formation	1
EPH-Ephrin signaling	1
Signaling by Interleukins	1
Innate Immune System	1
ESR-mediated signaling	1
Dengue Virus Infection	1
Axon guidance	1
Nervous system development	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
regulation of apoptotic process	2
peptidase activity	2
endopeptidase activity	2
intracellular organelle lumen	2
system development	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
protein metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
cell motility	1
cellular component disassembly	1
extracellular matrix organization	1
extracellular structure organization	1
external encapsulating structure organization	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
catabolic process	1
collagen metabolic process	1
endoderm formation	1
cell differentiation	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
DNA binding	1
positive regulation of binding	1
regulation of DNA binding	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
positive regulation of epithelial cell migration	1
keratinocyte migration	1
regulation of keratinocyte migration	1

Protein interactions and networks

STRING

6610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP9	TIMP1	P01033	999
MMP9	TIMP2	P16035	998
MMP9	CD44	P16070	996
MMP9	LCN2	P30150	996
MMP9	CTSG	P08311	987
MMP9	DMP1	Q13316	982
MMP9	ELANE	P08246	973
MMP9	ELN	P15502	972
MMP9	MPO	P05164	968
MMP9	THBS1	P07996	964
MMP9	THBS2	P35442	954
MMP9	TIMP3	P35625	942
MMP9	SPP1	P10451	942
MMP9	IL1B	P01584	932
MMP9	IL6	P05231	931

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ITGB1	ITGA5	psi-mi:“MI:0914”(association)	0.910
MMP9	MMP9	psi-mi:“MI:0407”(direct interaction)	0.760
MMP9	MMP9	psi-mi:“MI:0915”(physical association)	0.760
MMP9	TIMP1	psi-mi:“MI:0914”(association)	0.640
TIMP1	MMP9	psi-mi:“MI:2364”(proximity)	0.640
MMP9	VCAN	psi-mi:“MI:0407”(direct interaction)	0.600
MEP1A	MMP9	psi-mi:“MI:0194”(cleavage reaction)	0.560
MMP9	MEP1B	psi-mi:“MI:0194”(cleavage reaction)	0.560
MMP9	MEP1A	psi-mi:“MI:0194”(cleavage reaction)	0.560
MEP1B	MMP9	psi-mi:“MI:0194”(cleavage reaction)	0.560
set3	MMP9	psi-mi:“MI:0915”(physical association)	0.540
set3	MMP9	psi-mi:“MI:0407”(direct interaction)	0.540
VCAN	SRGN	psi-mi:“MI:0915”(physical association)	0.520
MMP9	APP	psi-mi:“MI:0570”(protein cleavage)	0.440
MMP9	SCUBE3	psi-mi:“MI:0570”(protein cleavage)	0.440
SCUBE3	MMP9	psi-mi:“MI:0570”(protein cleavage)	0.440
ELN	MMP9	psi-mi:“MI:0194”(cleavage reaction)	0.440
SRGN	MMP9	psi-mi:“MI:0407”(direct interaction)	0.440
MMP9	LCN2	psi-mi:“MI:0915”(physical association)	0.400
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
EGFL8	IGLC7	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
CYP3A43	HP	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): MMP9 (Co-localization), MMP9 (Affinity Capture-Western), CLU (Affinity Capture-Western), COL12A1 (Affinity Capture-MS), TIMP1 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), COL5A1 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), FN1 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL6A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), SCARA3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0Q3IBS1, I1H0V9, O08619, O18733, O54732, O82088, O88917, O94910, O97831, P00488, P08587, P13696, P14780, P22735, P22758, P23606, P30086, P31044, P41245, P41246, P51176, P51511, P52176, P52181, P52183, P54185, P93003, Q3YIX4, Q41261, Q5R4R0, Q656A5, Q80TR1, Q8MK67, Q8VIN1, Q8VWH2, Q93WI9, Q95220, Q9ASJ1, Q9D9G2, Q9FIT4

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

18 interactions.

A	Effect	B	Mechanism
USP6	“up-regulates quantity by expression”	MMP9	“transcriptional regulation”
SPRY4	“down-regulates activity”	MMP9
ETS1	“up-regulates quantity by expression”	MMP9	“transcriptional regulation”
NfKb-p65/p50	“up-regulates quantity by expression”	MMP9	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	MMP9	“transcriptional regulation”
SPDEF	“down-regulates quantity by repression”	MMP9	“transcriptional regulation”
MMP9	up-regulates	Cellular_extravasation
CCR6	“up-regulates activity”	MMP9
TIMP1	“down-regulates activity”	MMP9	binding
MMP9	up-regulates	TGFB1	cleavage
MMP9	“down-regulates quantity by destabilization”	HAPLN1	cleavage
MMP9	“down-regulates quantity by destabilization”	A2M	cleavage
MMP9	“down-regulates quantity by destabilization”	PZP	cleavage
A2M	“down-regulates activity”	MMP9	binding
PZP	“down-regulates activity”	MMP9	binding
MMP9	up-regulates	ECM_disassembly
MMP9	down-regulates	ECM

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Extracellular matrix organization	5	24.3×	9e-05
Hemostasis	5	13.9×	4e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	263
Likely benign	140
Benign	35

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2498120	NM_004994.3(MMP9):c.929del (p.Gly310fs)	Likely pathogenic
2498140	NM_004994.3(MMP9):c.151C>T (p.Arg51Cys)	Likely pathogenic

SpliceAI

1409 predictions. Top by Δscore:

Variant	Effect	Δscore
20:46009861:CACA:C	acceptor_loss	1.0000
20:46009863:CAGG:C	acceptor_loss	1.0000
20:46009864:A:AG	acceptor_gain	1.0000
20:46009864:A:G	acceptor_loss	1.0000
20:46009864:AG:A	acceptor_gain	1.0000
20:46009865:G:GG	acceptor_gain	1.0000
20:46009865:GG:G	acceptor_gain	1.0000
20:46009865:GGA:G	acceptor_gain	1.0000
20:46009865:GGAAT:G	acceptor_gain	1.0000
20:46010099:G:GG	donor_gain	1.0000
20:46010099:GTG:G	donor_loss	1.0000
20:46010100:T:G	donor_loss	1.0000
20:46010466:T:TA	acceptor_gain	1.0000
20:46010467:G:A	acceptor_gain	1.0000
20:46010474:A:AG	acceptor_gain	1.0000
20:46010474:AC:A	acceptor_gain	1.0000
20:46010475:C:A	acceptor_gain	1.0000
20:46010475:C:G	acceptor_gain	1.0000
20:46010478:TACAG:T	acceptor_loss	1.0000
20:46010479:ACAG:A	acceptor_gain	1.0000
20:46010480:C:G	acceptor_gain	1.0000
20:46010480:CAGG:C	acceptor_loss	1.0000
20:46010481:A:AG	acceptor_gain	1.0000
20:46010481:AG:A	acceptor_gain	1.0000
20:46010482:G:A	acceptor_gain	1.0000
20:46010482:G:GC	acceptor_gain	1.0000
20:46010482:GGA:G	acceptor_gain	1.0000
20:46010482:GGAT:G	acceptor_gain	1.0000
20:46010482:GGATC:G	acceptor_gain	1.0000
20:46010619:T:G	donor_gain	1.0000

AlphaMissense

4596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:46010942:T:C	F181L	0.999
20:46010943:T:G	F181C	0.999
20:46010944:C:A	F181L	0.999
20:46010944:C:G	F181L	0.999
20:46011029:T:A	W210R	0.999
20:46011029:T:C	W210R	0.999
20:46011031:G:C	W210C	0.999
20:46011031:G:T	W210C	0.999
20:46011689:G:C	W313C	0.999
20:46011689:G:T	W313C	0.999
20:46010075:G:C	W116C	0.998
20:46010075:G:T	W116C	0.998
20:46010553:T:A	W148R	0.998
20:46010553:T:C	W148R	0.998
20:46010619:T:C	F170L	0.998
20:46010621:T:A	F170L	0.998
20:46010621:T:G	F170L	0.998
20:46011012:T:C	F204S	0.998
20:46012255:G:C	W372C	0.998
20:46012255:G:T	W372C	0.998
20:46010073:T:A	W116R	0.997
20:46010073:T:C	W116R	0.997
20:46010555:G:C	W148C	0.997
20:46010555:G:T	W148C	0.997
20:46010620:T:G	F170C	0.997
20:46010975:T:C	F192L	0.997
20:46010977:T:A	F192L	0.997
20:46010977:T:G	F192L	0.997
20:46011258:G:C	W255C	0.997
20:46011258:G:T	W255C	0.997

dbSNP variants (sampled 300 via entrez): RS1000804505 (20:46007002 G>A), RS1002163924 (20:46007775 C>A), RS1003176758 (20:46009153 C>A,G,T), RS1003306278 (20:46008832 G>T), RS1004812364 (20:46011574 G>A,T), RS1004890991 (20:46010935 G>A,C,T), RS1005026375 (20:46010441 C>G,T), RS1005418458 (20:46016923 G>A,T), RS1005636653 (20:46013773 C>G), RS1005655705 (20:46007320 C>G,T), RS1005788282 (20:46012931 C>CA), RS1005968641 (20:46012089 T>C), RS1007016538 (20:46014077 G>T), RS1007487388 (20:46007700 A>G), RS1007663594 (20:46011994 C>G)

Disease associations

OMIM: gene MIM:120361 | disease phenotypes: MIM:613073

GenCC curated gene-disease

Disease	Classification	Inheritance
metaphyseal anadysplasia 2	Strong	Autosomal recessive
metaphyseal anadysplasia	Supportive	Autosomal dominant

Mondo (2): metaphyseal anadysplasia 2 (MONDO:0013113), metaphyseal anadysplasia (MONDO:0015177)

Orphanet (2): Metaphyseal anadysplasia (Orphanet:1040), Orofacial clefting syndrome (Orphanet:139039)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000944	Abnormal metaphysis morphology
HP:0001387	Joint stiffness
HP:0002814	Abnormality of the lower limb
HP:0002970	Genu varum
HP:0002979	Bowing of the legs
HP:0002983	Micromelia
HP:0003016	Metaphyseal widening
HP:0003025	Metaphyseal irregularity
HP:0003593	Infantile onset
HP:0004039	Abnormal ulnar metaphysis morphology
HP:0004322	Short stature
HP:0005930	Abnormal epiphysis morphology
HP:0006487	Bowing of the long bones
HP:0006501	Aplasia/Hypoplasia of the radius
HP:0040071	Abnormal morphology of ulna
HP:0100864	Short femoral neck

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001725_65	Inflammatory bowel disease	1.000000e-13
GCST003124_2	Mild influenza (H1N1) infection	2.000000e-08
GCST003219_44	Advanced age-related macular degeneration	2.000000e-10
GCST003877_9	Abdominal aortic aneurysm	2.000000e-17
GCST005554_4	Systemic sclerosis	1.000000e-07
GCST006585_260	Blood protein levels	2.000000e-14
GCST006979_543	Heel bone mineral density	3.000000e-09
GCST009731_62	Blood protein levels in cardiovascular risk	3.000000e-25
GCST010866_167	Coronary artery disease	7.000000e-11
GCST90013406_278	Liver enzyme levels (alkaline phosphatase)	1.000000e-26

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:1001492	atrophic macular degeneration
EFO:0009270	heel bone mineral density
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567771	Metaphyseal Anadysplasia 2 (supp.)
C537351	Metaphyseal anadysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095216 (PROTEIN FAMILY), CHEMBL321 (SINGLE PROTEIN), CHEMBL3885505 (PROTEIN FAMILY), CHEMBL4523972 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

26 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 799,369 (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
CHEMBL1200596	CHLOROXINE	4	1,792
CHEMBL1370	BUDESONIDE	4	72,936
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL4303669	ZOLEDRONIC ACID	4	523
CHEMBL447	SECOBARBITAL	4	11,739
CHEMBL476	DACARBAZINE	4	132,965
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL820	BUSULFAN	4	158,774
CHEMBL140	CURCUMIN	3	93,882
CHEMBL145	CAFFEIC ACID	3	36,305
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
CHEMBL2103847	TOSEDOSTAT	2	328
CHEMBL2107228	SOLIMASTAT	2	104
CHEMBL261932	TANOMASTAT	2
CHEMBL279786	BATIMASTAT	2
CHEMBL440498	CTS-1027	2
CHEMBL76222	REBIMASTAT	2
CHEMBL87223	AMINOQUINURIDE	2
CHEMBL297792	S-3304	1

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
MMP9 SERUM LEVELS	Bevacizumab	Inflammatory Breast Carcinoma	Resistance	CIViC B	EID1157

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3918242	MMP9		0.00	0
rs2274755	MMP9		0.00	0
rs2236416	MMP9		0.00	0
rs17577	MMP9		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
compound 1a [PMID: 15055993]	Inhibition	10.2	pKi
andecaliximab	Binding	9.66	pIC50
SL422	Inhibition	9.05	pKi
ilomastat	Inhibition	9.03	pIC50
compound 29e [PMID: 23631440]	Inhibition	8.82	pKi
AZD6605	Inhibition	8.7	pIC50
marimastat	Inhibition	8.52	pIC50
AZD1236	Inhibition	8.35	pIC50
CGS-27023A	Inhibition	8.32	pIC50
(R)-ND-336	Inhibition	7.72	pKi
SB-3CT	Inhibition	6.22	pKi
TP0556351	Inhibition	5.07	pIC50

Binding affinities (BindingDB)

273 measured of 380 human assays (380 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-methanesulfonyl-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide	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
(3R)-N-hydroxy-2-{[4-(4-methoxyphenyl)phenyl]methyl}-1,1-dioxo-1,2-thiazinane-3-carboxamide	KI	0.4 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
N-Pentafluorophenylsulfonyl-N-4-nitrobenzyl-glycine hydroxamate	KI	0.7 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	0.7 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	0.8 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	0.8 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}propanamide	KI	0.8 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxypropanamide	KI	0.9 nM
4-({[4-(3,4-Dimethylphenoxy)phenyl]sulfonyl}methyl)-N-hydroxy-1-prop-2-ynylpiperidine-4-carboxamide Hydrochloride	KI	0.9 nM
(3R)-N-hydroxy-1,1-dioxo-2-{[4-(pyridin-4-yl)phenyl]methyl}-1,2-thiazinane-3-carboxamide	KI	1 nM
(R)-N4-Hydroxy-N1-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide	IC50	1 nM	US-9487462: Inhibitors of matrix metalloproteinases
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}acetamide	KI	1.4 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	1.4 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxyacetamide	KI	1.5 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}acetamide	KI	1.5 nM
2-{(2-chlorophenyl)methylsulfonamido}-N-hydroxypropanamide	KI	1.5 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	1.9 nM
N-hydroxy-1-methanesulfonyl-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	2 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	2.4 nM
N-hydroxy-4-{[(4-phenoxybenzene)sulfonyl]methyl}piperidine-4-carboxamide hydrochloride	KI	2.8 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}propanamide	KI	2.9 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxypropanamide	KI	3.2 nM
(3R)-2-[(4-tert-butyl-1,1-biphenyl-4-yl)methyl]-N-hydroxy-1,2-thiazinane-3-carboxamide 1,1-dioxide	KI	3.2 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}acetamide	KI	3.7 nM
2-{(2-chlorophenyl)methylsulfonamido}-N-hydroxypropanamide	KI	3.7 nM
N-hydroxy-2-[(4-methoxy-1,1-biphenyl-4-yl)methyl]isothiazolidine-3-carboxamide 1,1-dioxide	KI	3.8 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxyacetamide	KI	3.9 nM
(3S)-4-{[4-(but-2-yn-1-yloxy)benzene]sulfonyl}-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide	IC50	4.7 nM
2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	10 nM
N-4-Methoxyphenylsulfonyl-N-benzyl-L-valine hydroxamate	KI	11 nM
hydroxamate deriv. B24	KI	12 nM
(4S)-5-[3-(carboxymethyl)piperidin-1-yl]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	12 nM	US-8691753
N-4-Methoxyphenylsulfonyl-N-2-nitrobenzyl-L-alanine hydroxamate	KI	13 nM
2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxypropanamide	KI	15 nM
N-hydroxy-2-[(4-methoxybenzene)[(2-nitrophenyl)methyl]sulfonamido]acetamide	KI	15 nM

ChEMBL bioactivities

3023 potent at pChembl≥5 of 3416 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL323090
10.52	IC50	0.03	nM	CHEMBL2064547
10.52	Ki	0.03	nM	PRINOMASTAT
10.32	IC50	0.048	nM	PRINOMASTAT
10.30	IC50	0.05	nM	CHEMBL2064549
10.30	IC50	0.05	nM	ILOMASTAT
10.22	IC50	0.06	nM	CHEMBL2064548
10.22	Ki	0.06	nM	CHEMBL61193
10.21	Ki	0.061	nM	CHEMBL61193
10.15	IC50	0.07	nM	CHEMBL2425941
10.15	IC50	0.07	nM	CHEMBL2425947
10.10	Ki	0.08	nM	CHEMBL355797
10.10	Ki	0.07943	nM	CHEMBL189690
10.04	IC50	0.092	nM	CHEMBL75164
10.04	IC50	0.092	nM	CHEMBL5270698
10.01	Ki	0.097	nM	CHEMBL56837
10.00	Ki	0.1	nM	CHEMBL425316
10.00	Ki	0.1	nM	CHEMBL190621
10.00	IC50	0.1	nM	ILOMASTAT
10.00	IC50	0.1	nM	CHEMBL1801396
10.00	IC50	0.1	nM	CHEMBL1801394
10.00	IC50	0.1	nM	CHEMBL1800089
9.96	IC50	0.11	nM	CTS-1027
9.96	Ki	0.11	nM	CHEMBL4797032
9.91	IC50	0.122	nM	CHEMBL4535400
9.89	Ki	0.13	nM	CHEMBL417537
9.85	IC50	0.14	nM	CHEMBL16519
9.85	IC50	0.14	nM	CHEMBL16554
9.82	IC50	0.15	nM	CHEMBL1801430
9.75	IC50	0.177	nM	ILOMASTAT
9.74	IC50	0.18	nM	CHEMBL1801398
9.74	IC50	0.18	nM	CHEMBL1771212
9.70	IC50	0.2	nM	CHEMBL2425944
9.70	IC50	0.2	nM	CHEMBL2425943
9.70	IC50	0.2	nM	PRINOMASTAT
9.70	Ki	0.2	nM	ILOMASTAT
9.70	IC50	0.2	nM	CHEMBL5285908
9.70	IC50	0.2	nM	CHEMBL5283673
9.70	IC50	0.2	nM	ILOMASTAT
9.70	IC50	0.2	nM	CHEMBL433426
9.70	IC50	0.2	nM	BATIMASTAT
9.70	IC50	0.2	nM	CHEMBL1771212
9.70	IC50	0.2	nM	CHEMBL1801431
9.70	IC50	0.2	nM	CHEMBL1801052
9.70	IC50	0.2	nM	CHEMBL1801412
9.70	IC50	0.2	nM	CHEMBL1916212
9.70	IC50	0.2	nM	CHEMBL296761
9.70	IC50	0.2	nM	CHEMBL47728
9.70	IC50	0.2	nM	CHEMBL102504
9.70	IC50	0.2	nM	CHEMBL106016

PubChem BioAssay actives

3001 with measured affinity, of 5176 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
4-benzylsulfanyl-2-[[2-(cyclohexylmethylamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-hydroxybutanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	108303: In vitro selective inhibition against Matrix metalloprotease-9 (MMP-9) using fluorimetric assay	ic50	<0.0001	uM
(2R)-2-[[1-(2-fluoroethyl)triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	675790: Inhibition of MMP9 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)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[(2S)-2-hydroxy-3-sulfanylpropyl]nonanamide	108018: Inhibition of matrix metalloprotease-9, gelatinase-B	ic50	0.0001	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	628298: Inhibition of MMP9	ic50	0.0001	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-(2-oxo-3-sulfanylpropyl)nonanamide	108018: Inhibition of matrix metalloprotease-9, gelatinase-B	ic50	0.0001	uM
N-[4-[(2R)-2-(hydroxycarbamoyl)cyclopentyl]sulfonylphenyl]-4-nitrobenzamide	1594392: Inhibition of MMP9 (unknown origin) pre-incubated for 5 mins before Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 fluorogenic substrate addition and measured over 30 mins by fluorometric assay	ic50	0.0001	uM
4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0001	uM
(2R)-N-hydroxy-1-[4-[(4-nitrobenzoyl)amino]phenyl]sulfonylpyrrolidine-2-carboxamide	1731966: Inhibition of MMP9 (unknown origin) using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 5 min followed by substrate addition and measured for 30 mins by fluorescence based assay	ki	0.0001	uM
N-[(3R)-3,4-dihydroxy-1-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylbutan-2-yl]-N-hydroxyformamide	1931012: Inhibition of MMP-9 (unknown origin) by fluorimetric assay	ic50	0.0001	uM
1-(2-ethoxyethyl)-N-hydroxy-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
N-hydroxy-4-[4-(4-methylsulfanylphenoxy)phenyl]sulfonyloxane-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
4-[4-(1,3-benzodioxol-5-yloxy)phenyl]sulfonyl-1-cyclopropyl-N-hydroxypiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
N-hydroxy-4-[4-(4-propan-2-yloxyphenoxy)phenyl]sulfonyloxane-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
N-hydroxy-4-[4-(4-hydroxyphenoxy)phenyl]sulfonyloxane-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
1-acetyl-N-hydroxy-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162789: Inhibition of human recombinant MMP9 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0001	uM
(2S,3R)-N-hydroxy-N’-[(2R)-3-(4-methoxyphenyl)-1-(methylamino)-1-oxopropan-2-yl]-2-methyl-3-(2-methylpropyl)butanediamide	108443: Inhibition of MMP-9 (Matrix metalloprotease-9)	ki	0.0001	uM
N-[(3S)-3,4-dihydroxy-1-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylbutan-2-yl]-N-hydroxyformamide	108303: In vitro selective inhibition against Matrix metalloprotease-9 (MMP-9) using fluorimetric assay	ic50	0.0001	uM
2-[ethoxy-(4-phenoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	108169: Inhibitory activity against matrix metalloprotease-9 (MMP-9)(gelatinase-B).	ki	0.0001	uM
2-[[4-(4-aminophenoxy)phenyl]-ethoxyphosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	108169: Inhibitory activity against matrix metalloprotease-9 (MMP-9)(gelatinase-B).	ki	0.0001	uM
(3R)-2-[[4-(4-aminophenoxy)phenyl]-ethoxyphosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	243286: Inhibition of MOCAc-Pro-Leu-Gly-Leu-A2p (Dnp)-Ala-Arg-NH2 binding to human matrix metalloprotease-9 (MMP-9)	ki	0.0001	uM
(3R)-2-[ethoxy-(4-phenoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	243286: Inhibition of MOCAc-Pro-Leu-Gly-Leu-A2p (Dnp)-Ala-Arg-NH2 binding to human matrix metalloprotease-9 (MMP-9)	ki	0.0001	uM
N-hydroxy-1-prop-2-ynyl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
N-hydroxy-1-propan-2-yl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	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	675790: Inhibition of MMP9 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	675790: Inhibition of MMP9 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-[2-[4-(3-fluoropropyl)triazol-1-yl]ethyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	769894: Inhibition of MMP-9 (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-[cyanomethyl-[4-(2-fluoroethoxy)phenyl]sulfonylamino]-N-hydroxy-3-methylbutanamide	769894: Inhibition of MMP-9 (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,3R,4R,5R)-N,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide	108166: Inhibition of human recombinant matrix metalloprotease 9	ki	0.0001	uM
N-hydroxy-1-(2-morpholin-4-ylethyl)-4-[4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
1-cyclopropyl-N-hydroxy-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
(2R,3R,4R,5S)-N,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide	108166: Inhibition of human recombinant matrix metalloprotease 9	ki	0.0001	uM
4-benzylsulfanyl-2-[[2-(dipyridin-2-ylmethylamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-hydroxybutanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0002	uM
4-benzylsulfanyl-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]amino]butanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0002	uM
N-hydroxy-1-(pyridin-2-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM
(2R)-N’-hydroxy-N-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]-2-nonylbutanediamide	108007: Activity against Matrix metalloprotease-9 (MMP-9).	ic50	0.0002	uM
2-[[2-(benzylamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-4-benzylsulfanyl-N-hydroxybutanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0002	uM
4-benzylsulfanyl-2-[[2-(cyclohexylamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-hydroxybutanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0002	uM
4-benzylsulfanyl-N-hydroxy-2-[[2-[(4-methoxyphenyl)methylamino]-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]butanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0002	uM
N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-propylamino]-3-methylsulfanylpropanamide	1930995: Inhibition of human MMP-9	ic50	0.0002	uM
(2S)-2-decyl-N’-hydroxy-N-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]butanediamide	1930993: Inhibition of MMP-9 (unknown origin) assessed as inhibition constant using Mca-Pro-Leu-Gly-Dpa-Ala-Arg-NH2 substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by fluorimetric analysis	ic50	0.0002	uM
1-cyclopropyl-4-[4-(4-ethoxyphenoxy)phenyl]sulfonyl-N-hydroxypiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM
1-cyclopropyl-N-hydroxy-4-[4-(4-propan-2-yloxyphenoxy)phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM
N-hydroxy-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM
(2R)-N-hydroxy-3-methyl-2-[[2-oxo-2-[2-(4-sulfamoylphenyl)ethylamino]ethyl]-(4-phenoxyphenyl)sulfonylamino]butanamide	413959: Inhibition of MMP9	ic50	0.0002	uM
(2S)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]-4-[(4-phenylphenyl)methylsulfanyl]butanamide	104919: Inhibition of matrix metalloprotease-9	ic50	0.0002	uM
(2S)-N-hydroxy-2-[2-methylpropyl-(4-phenylphenyl)sulfonylamino]-4-methylsulfanylbutanamide	104919: Inhibition of matrix metalloprotease-9	ic50	0.0002	uM
4-[(4-cyclohex-2-en-1-ylphenyl)methylsulfanyl]-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]butanamide	108012: In vitro inhibition of human matrix metalloprotease-9	ic50	0.0002	uM
N-hydroxy-1-methyl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604453: Inhibition of human MMP9 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	increases expression, increases secretion, increases activity, increases reaction, affects cotreatment (+2 more)	53
Resveratrol	affects reaction, increases secretion, decreases secretion, increases expression, affects cotreatment (+6 more)	36
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases secretion, increases expression, increases activity, decreases expression (+2 more)	25
Arsenic Trioxide	affects reaction, decreases response to substance, affects cotreatment, decreases activity, decreases expression (+8 more)	22
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, decreases activity, increases secretion, increases reaction, affects cotreatment (+3 more)	21
bisphenol A	affects cotreatment, decreases expression, increases activity, decreases reaction, increases secretion (+6 more)	19
sodium arsenite	increases expression, increases activity, decreases expression, affects cotreatment, increases abundance (+2 more)	19
SB 203580	decreases expression, decreases activity, affects cotreatment, increases activity, increases expression (+3 more)	18
Curcumin	decreases reaction, increases expression, increases reaction, increases activity, decreases activity (+2 more)	17
Estradiol	decreases reaction, increases expression, decreases expression, increases activity, decreases activity (+3 more)	16
pyrazolanthrone	increases activity, increases secretion, increases expression, decreases activity, increases reaction (+4 more)	15
U 0126	increases activity, decreases expression, decreases reaction, increases expression, increases secretion	14
Lipopolysaccharides	decreases reaction, increases reaction, increases activity, increases expression, affects cotreatment (+3 more)	14
Quercetin	increases reaction, decreases activity, decreases secretion, increases expression, decreases expression (+5 more)	14
Cadmium	increases activity, affects expression, decreases activity, decreases secretion, increases secretion (+5 more)	13
Cadmium Chloride	decreases reaction, increases reaction, affects reaction, increases secretion, increases abundance (+5 more)	12
Acetylcysteine	increases expression, decreases expression, decreases secretion, decreases activity, decreases reaction (+1 more)	11
Simvastatin	decreases expression, decreases reaction, increases expression, increases secretion, increases activity (+3 more)	11
Particulate Matter	increases abundance, increases expression, decreases reaction, increases activity, increases reaction (+1 more)	11
Benzo(a)pyrene	increases expression, increases methylation, affects reaction, decreases reaction, affects expression (+2 more)	10
Plant Extracts	decreases reaction, increases expression, increases activity, decreases activity, decreases expression (+3 more)	10
Tetrachlorodibenzodioxin	affects reaction, increases activity, increases expression, decreases reaction, affects binding	9
Tobacco Smoke Pollution	decreases expression, affects cotreatment, decreases reaction, increases expression, increases activity (+2 more)	9
Arsenic	increases activity, increases secretion, decreases abundance, decreases reaction, increases expression (+3 more)	8
Cisplatin	decreases response to substance, increases expression, affects cotreatment, decreases expression, increases activity (+5 more)	8
Hydrogen Peroxide	affects reaction, decreases expression, decreases reaction, increases expression, increases activity (+1 more)	8
diallyl trisulfide	affects expression, decreases activity, decreases expression, decreases reaction, increases reaction	7
cordycepin	decreases reaction, increases expression, increases secretion, decreases activity, decreases expression (+1 more)	7
Glucose	decreases expression, decreases activity, increases reaction, affects binding, increases activity (+5 more)	7
hydroquinone	increases expression, decreases reaction, increases secretion, increases reaction, affects reaction	6

ChEMBL screening assays

713 unique, capped per target: 685 binding, 20 admet, 8 functional

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
CHEMBL4000933	ADMET	Inhibition of APMA-activated recombinant human MMP-9 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

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8KP	Abcam HCT 116 MMP9 KO	Cancer cell line	Male
CVCL_B8Z0	Abcam MCF-7 MMP9 KO	Cancer cell line	Female
CVCL_B9MX	Abcam A-549 MMP9 KO	Cancer cell line	Male
CVCL_D1TL	Abcam U-87MG MMP9 KO	Cancer cell line	Male
CVCL_D9KJ	Ubigene HEK293 MMP9 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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