MMP2

Summary

MMP2 (matrix metallopeptidase 2, HGNC:7166) is a protein-coding gene on chromosome 16q12.2, encoding 72 kDa type IV collagenase (P08253). Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. In precision oncology, MMP2 SERUM LEVELS confers sensitivity to Bevacizumab in Inflammatory Breast Carcinoma (CIViC Level B); 1 further curated variant–drug associations are listed below.

This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 4313 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multicentric osteolysis, nodulosis, and arthropathy (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 465 total — 22 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 87
• Druggable target: yes — 26 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• MANE Select transcript: NM_004530

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7166
Approved symbol	MMP2
Name	matrix metallopeptidase 2
Location	16q12.2
Locus type	gene with protein product
Status	Approved
Aliases	MMP-2, TBE-1
Ensembl gene	ENSG00000087245
Ensembl biotype	protein_coding
OMIM	120360
Entrez	4313

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000219070, ENST00000437642, ENST00000543485, ENST00000564864, ENST00000566564, ENST00000568715, ENST00000570283, ENST00000570308

RefSeq mRNA: 5 — MANE Select: NM_004530 NM_001127891, NM_001302508, NM_001302509, NM_001302510, NM_004530

CCDS: CCDS10752, CCDS45487, CCDS76869

Canonical transcript exons

ENST00000219070 — 13 exons

Exon	Start	End
ENSE00000396666	55488543	55488716
ENSE00000684376	55484016	55484164
ENSE00000684379	55485299	55485427
ENSE00000684383	55485604	55485777
ENSE00000684389	55489651	55489824
ENSE00000684415	55493158	55493293
ENSE00000684425	55496926	55497062
ENSE00000684426	55498289	55498448
ENSE00000684427	55502779	55502888
ENSE00001045278	55479198	55479632
ENSE00001170187	55491801	55491956
ENSE00001931477	55505339	55506691
ENSE00003564331	55482909	55483135

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 306.8157 / max 6888.4724, expressed in 1369 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154124	277.0450	1352
154123	22.6892	1079
154122	2.6354	634
154149	2.1292	513
154137	1.7209	510
154136	0.5960	285

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.96	gold quality
gall bladder	UBERON:0002110	99.80	gold quality
mucosa of stomach	UBERON:0001199	99.71	gold quality
endocervix	UBERON:0000458	99.54	gold quality
skin of hip	UBERON:0001554	99.48	gold quality
smooth muscle tissue	UBERON:0001135	99.43	gold quality
colonic epithelium	UBERON:0000397	99.30	gold quality
right lung	UBERON:0002167	99.08	gold quality
left uterine tube	UBERON:0001303	99.06	gold quality
descending thoracic aorta	UBERON:0002345	99.05	gold quality
right ovary	UBERON:0002118	99.02	gold quality
upper leg skin	UBERON:0004262	98.98	gold quality
cartilage tissue	UBERON:0002418	98.97	gold quality
ascending aorta	UBERON:0001496	98.96	gold quality
thoracic aorta	UBERON:0001515	98.96	gold quality
skin of leg	UBERON:0001511	98.93	gold quality
body of uterus	UBERON:0009853	98.91	gold quality
left ovary	UBERON:0002119	98.87	gold quality
omental fat pad	UBERON:0010414	98.81	gold quality
peritoneum	UBERON:0002358	98.80	gold quality
ectocervix	UBERON:0012249	98.80	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.72	gold quality
periodontal ligament	UBERON:0008266	98.68	gold quality
synovial joint	UBERON:0002217	98.67	gold quality
upper lobe of left lung	UBERON:0008952	98.64	gold quality
upper arm skin	UBERON:0004263	98.61	gold quality
upper lobe of lung	UBERON:0008948	98.58	gold quality
right coronary artery	UBERON:0001625	98.56	gold quality
decidua	UBERON:0002450	98.56	gold quality
coronary artery	UBERON:0001621	98.47	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-10596	yes	2228.41
E-MTAB-8142	yes	2082.65
E-CURD-126	yes	1915.18
E-MTAB-6701	yes	1138.39
E-GEOD-134144	yes	1016.76
E-MTAB-10662	yes	940.21
E-GEOD-135922	yes	801.88
E-MTAB-7008	yes	526.06
E-MTAB-8381	yes	342.63
E-MTAB-10287	yes	126.43
E-HCAD-1	yes	97.14
E-MTAB-8410	yes	73.76
E-HCAD-11	yes	58.28
E-HCAD-10	yes	55.15
E-MTAB-6678	yes	28.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ATF1, ATF2, ATF3, BMPR1A, CEBPE, CEBPG, CREB1, CTNNB1, CTSH, DDIT3, DNMT1, EGR1, ESR1, ESR2, ETS1, ETS2, ETV4, ETV5, ETV7, EZH2, FOS, FOSB, FOSL1, FOXC1, FOXM1, FOXO1, FOXP3, GATA2, GATA4, GCM1, GLI2, HDAC3, HESX1, HIF1A, HMGA1, HNF4A, HOXA11

miRNA regulators (miRDB)

95 targeting MMP2, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
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-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-1825	99.72	68.11	1089

Literature-anchored findings (GeneRIF, showing 40)

• involvement of MMPs in microinvasive carcinomas (PMID:11168762)
• non-steroidal anti-inflammatory drugs suppress MMP-2 expression via repression of transcription (PMID:11728453)
• Activated matrix metalloproteinase-2–a potential marker of prognosis for epithelial ovarian cancer. (PMID:11748988)
• 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)
• 17beta-estradiol had no influence on production in MG-63 cells or human osteoblast cultures (PMID:11762702)
• Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts. (PMID:11782389)
• design, synthesis and characterization of potent slow-binding inhibitors (PMID:11790786)
• repression of expression by ATF3 (PMID:11792711)
• in differentiating trophoblasts Nitric Oxide regulates the induction of MMP-2 and MMP-9 required for invasion during embryo implantation (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)
• Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in nonsmall cell lung carcinomas (PMID:11844598)
• 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-2 expression seemed to have an important role to play in the epithelial differentiation of tumour cells in synovial sarcoma. (PMID:11895494)
• SB203580, a p38 MAP kinase inhibitor, reduces MMP-2 expression in melanoma cell line MeWO. (PMID:11918086)
• increasing expression and endometrial carcinoma appear closely related (PMID:11920503)
• A study of the col-1 module of MMP2; structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains. (PMID:11928808)
• Levels of MMP2 mRNA were reduced in two neuroblastoma clones treated with 300 nM PAF, which was accompanied by an inhibition of invasiveness through Matrigel and by a promotion of differentiation. (PMID:11928813)
• activation by overexpression of manganese superoxide dismutase in human breast cancer MCF-7 cells involves reactive oxygen species (PMID:11929863)
• activation associated with malignant lung cell phenotype; correlation between low hemoglobin level and T/N ratio of MMP-2 may indicate indicate significance of MMP-2 for angiogenesis (PMID:11935310)
• Significantly increased activity of MMP-2 was recognized in tumors showing tenascin-C degradation. (PMID:11948127)
• expression level of MMP-2 mRNA may regulate with invasion ability of cervical cancer (PMID:11956628)
• Increased gelatinase activity in Systemic Sclerosis fibroblasts seems to be regulated at translational and/or post-translational level. (PMID:12007723)
• 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)
• N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells (PMID:12085233)
• MMP2 inhibition by NSAIDs via suppression of the ERK/Sp1-mediated transcription. (PMID:12087091)
• Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism. (PMID:12115722)
• Coexpression of glucose transporter 1 and matrix metalloproteinase-2 in human cancers (PMID:12122099)
• role in A549 cell migration on laminin-10/11 (PMID:12147229)
• solution structure of a catalytic domain of MMP-2 complexed with a hydroxamic acid inhibitor (SC-74020), determined by three-dimensional heteronuclear NMR spectroscopy (PMID:12147339)
• data indicate the involvement of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the cervical ripening process (PMID:12193399)
• calcium regulates MMP2 activation in a MT1-MMP-dependent manner in oral squamous cell carcinoma cells (PMID:12194986)
• Apoptosis of human hepatic myofibroblasts promotes activation of matrix metalloproteinase-2. (PMID:12198653)
• Human fibronectin and MMP-2 collagen binding domains compete for collagen binding sites and modify cellular activation of MMP-2. (PMID:12225805)
• MMP2 activation is increased by Eph B4 receptor stimulation in human cells (PMID:12235151)
• endometrium from women with endometriosis expressed higher levels of MMP-2 and MT1-MMP and lower levels of TIMP-2 than did endometrium from normal women (PMID:12372458)
• role of acidic residues in TIMP-2 and TIMP-4 in binding hemopexin C domain (PMID:12374789)
• MMP-9 level and TIMP-1 levels increased after birth but are not linked to bronchopulmonary dysplasia outcome; low MMP-2 level at birth is associated with the development of BPD (PMID:12376362)
• MMP2 may play a pivotal role in the formation of capillarylike tubular structures in a collagen-containing fibrin matrix in vitro and may be involved in angiogenesis in a fibrinous exudate in vivo. (PMID:12393408)
• Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates enzyme and cd44 in cox-2-dependent invasion (PMID:12393872)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp2	ENSDARG00000017676
mus_musculus	Mmp2	ENSMUSG00000031740
rattus_norvegicus	Mmp2	ENSRNOG00000016695
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), 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

72 kDa type IV collagenase — P08253 (reviewed: P08253)

Alternative names: 72 kDa gelatinase, Gelatinase A, Matrix metalloproteinase-2, TBE-1

All UniProt accessions (5): P08253, H3BR66, H3BS34, H3BV48, J3KRB7

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14. PEX, the C-terminal non-catalytic fragment of MMP2, possesses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels. Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.

Subunit / interactions. Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B.

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

Tissue specificity. Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate.

Post-translational modifications. Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3.

Disease relevance. Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600] An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. The disease is caused by variants affecting the gene represented in this entry.

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

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.

Induction. Aspirin appears to inhibit expression.

Miscellaneous. Induced by oxidative stress.

Similarity. Belongs to the peptidase M10A family.

Isoforms (3)

UniProt ID	Names	Canonical?
P08253-1	1	yes
P08253-2	2
P08253-3	3

RefSeq proteins (5): NP_001121363, NP_001289437, NP_001289438, NP_001289439, NP_004521* (*=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 3.4.24.24 — gelatinase A (BRENDA: 14 organisms, 115 substrates, 168 inhibitors, 48 Km, 46 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PEPTIDE A13	1.3–2.5	3
PEPTIDE A13R	0.1–0.4	3
PEPTIDE A3	1.2–3.6	3
PEPTIDE A34	2.2–4.3	3
PEPTIDE B74	0.2–2.2	3
PEPTIDE C9	0.9–4.4	3
AC-PRO-LEU-GLY-[2-MERCAPTO-4-METHYLPENTANOYL]-LE	0.136–0.172	2
DNP-PRO-BETA-CYCLOHEXYL-ALA-GLY-CYS(ME)-HIS-ALA-	0.059–0.118	2
MCA-PRO-LEU-GLY-LEU-DAP-ALA-ARG-NH2	0.0057–0.0099	2
MOACPLGLA2PR(DNP)-AR-NH2	0.0015–0.0031	2
TYPE I COLLAGEN	0.0085	2
ACETYL-PRO-LEU-GLY-THIOESTER-LEU-LEU-GLY ETHYL E	0.134	1
ALPHA1(V)436-447 FTHP	0.0044	1
FIBRINOGEN	0.159	1
FTHP-3	0.0172	1

UniProt features (136 total): strand 48, binding site 23, turn 13, helix 12, sequence variant 9, disulfide bond 7, repeat 4, region of interest 4, domain 3, sequence conflict 3, chain 2, glycosylation site 2, splice variant 2, signal peptide 1, propeptide 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
3AYU	X-RAY DIFFRACTION	2
7XJO	X-RAY DIFFRACTION	2
1GEN	X-RAY DIFFRACTION	2.15
8H78	X-RAY DIFFRACTION	2.4
1RTG	X-RAY DIFFRACTION	2.6
1EAK	X-RAY DIFFRACTION	2.66
1CK7	X-RAY DIFFRACTION	2.8
1QIB	X-RAY DIFFRACTION	2.8
7XGJ	X-RAY DIFFRACTION	2.8
1GXD	X-RAY DIFFRACTION	3.1
1CXW	SOLUTION NMR
1HOV	SOLUTION NMR
1J7M	SOLUTION NMR
1KS0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08253-F1	90.31	0.79

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): 404

Ligand- & substrate-binding residues (23): 102 (in inhibited form); 134; 168; 178; 180; 185; 186; 193; 200; 202; 204; 206 …

Disulfide bonds (7): 233–259, 247–274, 291–317, 305–332, 349–375, 363–390, 469–660

Glycosylation sites (2): 573, 642

Function

Pathways and Gene Ontology

Reactome pathways

20 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-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-392499	Metabolism of proteins
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-9675108	Nervous system development

MSigDB gene sets: 722 (showing top): VALK_AML_WITH_FLT3_ITD, GSE45365_NK_CELL_VS_BCELL_DN, MODULE_172, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, GOBP_BONE_TRABECULA_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_RESPONSE_TO_ESTRADIOL

GO Biological Process (53): angiogenesis (GO:0001525), ovarian follicle development (GO:0001541), ovulation from ovarian follicle (GO:0001542), luteinization (GO:0001553), response to hypoxia (GO:0001666), blood vessel maturation (GO:0001955), intramembranous ossification (GO:0001957), proteolysis (GO:0006508), negative regulation of cell adhesion (GO:0007162), heart development (GO:0007507), parturition (GO:0007567), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), peripheral nervous system axon regeneration (GO:0014012), response to activity (GO:0014823), cell migration (GO:0016477), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), extracellular matrix organization (GO:0030198), positive regulation of cell migration (GO:0030335), collagen catabolic process (GO:0030574), response to retinoic acid (GO:0032526), cellular response to reactive oxygen species (GO:0034614), response to nicotine (GO:0035094), endodermal cell differentiation (GO:0035987), response to hydrogen peroxide (GO:0042542), response to estrogen (GO:0043627), negative regulation of vasoconstriction (GO:0045906), ephrin receptor signaling pathway (GO:0048013), macrophage chemotaxis (GO:0048246), tissue remodeling (GO:0048771), response to electrical stimulus (GO:0051602), response to hyperoxia (GO:0055093), face morphogenesis (GO:0060325), bone trabecula formation (GO:0060346), prostate gland epithelium morphogenesis (GO:0060740), trophoblast cell migration (GO:0061450), cellular response to amino acid stimulus (GO:0071230), cellular response to interleukin-1 (GO:0071347), cellular response to estradiol stimulus (GO:0071392)

GO Molecular Function (10): fibronectin binding (GO:0001968), endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), mitochondrion (GO:0005739), plasma membrane (GO:0005886), sarcomere (GO:0030017), extracellular matrix (GO:0031012), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	1
Metabolism of proteins	1
EPH-Ephrin signaling	1
Signaling by Interleukins	1
ESR-mediated signaling	1
MAPK family signaling cascades	1
Immune System	1
Axon guidance	1
Nervous system development	1
Cytokine Signaling in Immune system	1
Signaling by Nuclear Receptors	1
Signal Transduction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
female gonad development	3
ovulation cycle process	2
protein metabolic process	2
peptidase activity	2
endopeptidase activity	2
intracellular membrane-bounded organelle	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
anatomical structure development	1
ovulation	1
response to stress	1
response to decreased oxygen levels	1
blood vessel development	1
anatomical structure maturation	1
direct ossification	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
animal organ development	1
circulatory system development	1
multi-organism reproductive process	1
multi-multicellular organism process	1
response to chemical	1
response to external stimulus	1
response to abiotic stimulus	1
axon regeneration	1
response to stimulus	1
cell motility	1
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 migration	1
positive regulation of cell motility	1
protein binding	1
metallopeptidase activity	1
serine-type peptidase activity	1

Protein interactions and networks

STRING

4424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP2	TIMP2	P16035	999
MMP2	TIMP1	P01033	994
MMP2	MMP14	P50281	961
MMP2	CD44	P16070	942
MMP2	IBSP	P21815	935
MMP2	TIMP4	Q99727	918
MMP2	TIMP3	P35625	909
MMP2	HPX	P02790	874
MMP2	CLCN3	P51790	863
MMP2	ELN	P15502	858
MMP2	TGFB1	P01137	850
MMP2	AKT1	P31749	844
MMP2	SPP1	P10451	836
MMP2	CDH2	P19022	822
MMP2	CXCL8	P10145	814

IntAct

72 interactions, top by confidence:

A	B	Type	Score
COL5A1	MMP2	psi-mi:“MI:0915”(physical association)	0.780
MMP2	COL5A1	psi-mi:“MI:0915”(physical association)	0.780
WFDC2	ANXA2	psi-mi:“MI:0914”(association)	0.740
WFDC2	ANXA2	psi-mi:“MI:0915”(physical association)	0.740
TIMP2	MMP2	psi-mi:“MI:0407”(direct interaction)	0.690
MMP2	COL4A1	psi-mi:“MI:0914”(association)	0.640
PCSK9	MMP2	psi-mi:“MI:0194”(cleavage reaction)	0.620
PCSK9	MMP2	psi-mi:“MI:0407”(direct interaction)	0.620
APP	MMP2	psi-mi:“MI:0407”(direct interaction)	0.620
MMP2	APP	psi-mi:“MI:0570”(protein cleavage)	0.620
USP12	PHLPP1	psi-mi:“MI:0914”(association)	0.570
MMP2	REL	psi-mi:“MI:0915”(physical association)	0.560
APP	MMP2	psi-mi:“MI:0915”(physical association)	0.560
MMP2	Pcsk9	psi-mi:“MI:0194”(cleavage reaction)	0.440
MMP2		psi-mi:“MI:0194”(cleavage reaction)	0.440

BioGRID (107): BACE1 (Co-localization), A2M (Co-localization), TGFB1 (Co-localization), PAK4 (Affinity Capture-Western), MMP2 (Affinity Capture-Western), PAK4 (Reconstituted Complex), ITGAV (Affinity Capture-Western), ITGB3 (Affinity Capture-Western), MMP2 (Synthetic Growth Defect), COL14A1 (Affinity Capture-MS), COL12A1 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), FN1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), HIST2H2AC (Affinity Capture-MS)

ESM2 similar proteins: B8A4W9, C0HJB0, C0HK23, C0HK24, E1C3U7, I0CME7, O08524, O70244, P01410, P01415, P01418, P08253, P0CB06, P0DKS3, P14780, P17945, P19637, P22031, P24020, P26322, P31226, P33434, P33436, P34710, P41245, P50282, P50757, P54097, P83302, P86177, P86178, P86422, P97435, P98072, P98073, Q08048, Q20911, Q29485, Q3UV74, Q5EA66

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

22 interactions.

A	Effect	B	Mechanism
NODAL	“up-regulates quantity by expression”	MMP2	“transcriptional regulation”
RUNX2	“up-regulates quantity by expression”	MMP2	“transcriptional regulation”
NME1	“down-regulates quantity by repression”	MMP2	“transcriptional regulation”
TP53	“up-regulates quantity by expression”	MMP2	“transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	MMP2	“transcriptional regulation”
MMP2	up-regulates	TGFB1	cleavage
MMP2	“up-regulates quantity”	LRP2	binding
MMP2	“up-regulates activity”	Laminin-5	cleavage
MMP2	“up-regulates activity”	LAMC2	cleavage
MMP2	“down-regulates quantity by destabilization”	HAPLN1	cleavage
MMP25	“up-regulates activity”	MMP2	cleavage
MMP2	“down-regulates quantity by destabilization”	DCN	cleavage
MMP2	“down-regulates quantity by destabilization”	A2M	cleavage
MMP2	“down-regulates quantity by destabilization”	PZP	cleavage
A2M	“down-regulates activity”	MMP2	binding
PZP	“down-regulates activity”	MMP2	binding
MMP2	up-regulates	ECM_disassembly
MMP2	down-regulates	ECM

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
Collagen biosynthesis and modifying enzymes	6	32.0×	8e-06
Assembly of collagen fibrils and other multimeric structures	5	31.3×	3e-05
ECM proteoglycans	6	28.2×	8e-06
Non-integrin membrane-ECM interactions	5	24.1×	9e-05
Integrin cell surface interactions	5	21.0×	1e-04
Extracellular matrix organization	7	13.8×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	6	38.5×	6e-06

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	11
Uncertain significance	186
Likely benign	131
Benign	65

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323283	NM_004530.6(MMP2):c.1289del (p.Asn430fs)	Pathogenic
1332689	NM_004530.6(MMP2):c.910_916del (p.Ser304fs)	Pathogenic
1332865	NM_004530.6(MMP2):c.789C>A (p.Tyr263Ter)	Pathogenic
1335213	NM_004530.6(MMP2):c.865C>T (p.Gln289Ter)	Pathogenic
1341994	NM_004530.6(MMP2):c.301C>T (p.Arg101Cys)	Pathogenic
144256	GRCh38/hg38 16q12.2-21(chr16:55457477-63841622)x1	Pathogenic
1457670	NC_000016.9:g.(?55513392)(55539354_?)del	Pathogenic
1685950	NM_004530.6(MMP2):c.691G>T (p.Glu231Ter)	Pathogenic
17108	NM_004530.6(MMP2):c.302G>A (p.Arg101His)	Pathogenic
17109	NM_004530.6(MMP2):c.732C>A (p.Tyr244Ter)	Pathogenic
17111	NM_004530.6(MMP2):c.1199_1201del (p.Val400del)	Pathogenic
17112	NM_004530.6(MMP2):c.1357del (p.Gly454fs)	Pathogenic
195227	NM_004530.6(MMP2):c.265del (p.Asp90fs)	Pathogenic
198809	NM_004530.6(MMP2):c.1287del (p.Asn430fs)	Pathogenic
2031305	NM_004530.6(MMP2):c.1743_1744dup (p.Ile582fs)	Pathogenic
3003362	NM_004530.6(MMP2):c.1081G>T (p.Glu361Ter)	Pathogenic
3615226	NM_004530.6(MMP2):c.481C>T (p.Arg161Ter)	Pathogenic
3678169	NM_004530.6(MMP2):c.1160G>A (p.Trp387Ter)	Pathogenic
3777151	NM_004530.6(MMP2):c.348del (p.Lys116fs)	Pathogenic
3908086	NM_004530.6(MMP2):c.1161G>A (p.Trp387Ter)	Pathogenic
4722790	NM_004530.6(MMP2):c.799A>T (p.Lys267Ter)	Pathogenic
915430	NM_004530.6(MMP2):c.1648C>T (p.Arg550Ter)	Pathogenic
1299550	NM_004530.6(MMP2):c.529G>A (p.Glu177Lys)	Likely pathogenic
1299551	NM_004530.6(MMP2):c.1456TTC[2] (p.Phe488del)	Likely pathogenic
1332856	NM_004530.6(MMP2):c.306C>A (p.Cys102Ter)	Likely pathogenic
1512999	NC_000016.9:g.(?55515327)(55516985_?)del	Likely pathogenic
17110	NM_004530.6(MMP2):c.1210G>A (p.Glu404Lys)	Likely pathogenic
2082094	NM_004530.6(MMP2):c.1770-1_1774del	Likely pathogenic
2636522	NM_004530.6(MMP2):c.1336+2T>G	Likely pathogenic
3336911	NM_004530.6(MMP2):c.1188C>A (p.Ser396Arg)	Likely pathogenic

SpliceAI

1854 predictions. Top by Δscore:

Variant	Effect	Δscore
16:55479630:GTG:G	donor_gain	1.0000
16:55482895:T:TA	acceptor_gain	1.0000
16:55482898:A:AG	acceptor_gain	1.0000
16:55482899:T:G	acceptor_gain	1.0000
16:55482904:TTCA:T	acceptor_loss	1.0000
16:55482906:CA:C	acceptor_loss	1.0000
16:55482907:A:AG	acceptor_gain	1.0000
16:55482908:G:GC	acceptor_loss	1.0000
16:55482908:G:GG	acceptor_gain	1.0000
16:55482908:GC:G	acceptor_gain	1.0000
16:55482908:GCA:G	acceptor_gain	1.0000
16:55482908:GCAA:G	acceptor_gain	1.0000
16:55482908:GCAAT:G	acceptor_gain	1.0000
16:55482910:A:AG	acceptor_gain	1.0000
16:55483132:ACAGG:A	donor_loss	1.0000
16:55483134:AGGTG:A	donor_loss	1.0000
16:55483135:GGTGC:G	donor_loss	1.0000
16:55483136:G:C	donor_loss	1.0000
16:55485292:GTTTC:G	acceptor_loss	1.0000
16:55485293:TTTCA:T	acceptor_loss	1.0000
16:55485294:TTCA:T	acceptor_loss	1.0000
16:55485295:TCA:T	acceptor_loss	1.0000
16:55485296:CA:C	acceptor_loss	1.0000
16:55485297:A:AG	acceptor_gain	1.0000
16:55485298:G:GA	acceptor_gain	1.0000
16:55485298:G:GT	acceptor_loss	1.0000
16:55485298:GA:G	acceptor_gain	1.0000
16:55485298:GAGC:G	acceptor_gain	1.0000
16:55485423:CCAAG:C	donor_loss	1.0000
16:55485424:CAAG:C	donor_loss	1.0000

AlphaMissense

4389 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:55483059:T:A	C102S	1.000
16:55483059:T:C	C102R	1.000
16:55483060:G:A	C102Y	1.000
16:55483060:G:C	C102S	1.000
16:55483110:T:A	W119R	1.000
16:55483110:T:C	W119R	1.000
16:55483112:G:C	W119C	1.000
16:55483112:G:T	W119C	1.000
16:55484086:T:A	W151R	1.000
16:55484086:T:C	W151R	1.000
16:55485319:T:C	F184L	1.000
16:55485320:T:G	F184C	1.000
16:55485321:T:A	F184L	1.000
16:55485321:T:G	F184L	1.000
16:55485346:C:G	H193D	1.000
16:55485348:T:A	H193Q	1.000
16:55485348:T:G	H193Q	1.000
16:55485352:T:C	F195L	1.000
16:55485353:T:G	F195C	1.000
16:55485354:C:A	F195L	1.000
16:55485354:C:G	F195L	1.000
16:55485389:T:C	F207S	1.000
16:55485392:A:T	D208V	1.000
16:55485406:T:A	W213R	1.000
16:55485406:T:C	W213R	1.000
16:55485407:G:C	W213S	1.000
16:55485408:G:C	W213C	1.000
16:55485408:G:T	W213C	1.000
16:55491831:A:T	E404V	1.000
16:55491832:G:C	E404D	1.000

dbSNP variants (sampled 300 via entrez): RS1000054420 (16:55477643 C>A,G,T), RS1000206596 (16:55500540 G>A,C), RS1000214241 (16:55491552 T>C), RS1000241037 (16:55500275 A>G), RS1000351109 (16:55493721 G>A), RS1000626247 (16:55506572 C>A), RS1001123940 (16:55492606 C>T), RS1001150817 (16:55501467 T>A), RS1001493371 (16:55495839 G>A), RS1001521640 (16:55480401 C>G,T), RS1001532018 (16:55505066 G>A), RS1001858767 (16:55479216 C>T), RS1002398323 (16:55478965 G>T), RS1002987296 (16:55492522 T>A,C), RS1002999418 (16:55486689 A>T)

Disease associations

OMIM: gene MIM:120360 | disease phenotypes: MIM:259600

GenCC curated gene-disease

Disease	Classification	Inheritance
multicentric osteolysis, nodulosis, and arthropathy	Strong	Autosomal recessive
multicentric osteolysis-nodulosis-arthropathy spectrum	Supportive	Autosomal recessive

Mondo (4): multicentric osteolysis-nodulosis-arthropathy spectrum (MONDO:0018298), multicentric osteolysis, nodulosis, and arthropathy (MONDO:0009809), intellectual disability (MONDO:0001071), lip and oral cavity carcinoma (MONDO:0023644)

Orphanet (3): Torg-Winchester syndrome (Orphanet:3460), Multicentric osteolysis-nodulosis-arthropathy spectrum (Orphanet:371428), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0000212	Gingival overgrowth
HP:0000248	Brachycephaly
HP:0000280	Coarse facial features
HP:0000315	Abnormality of the orbital region
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000414	Bulbous nose
HP:0000446	Narrow nasal bridge
HP:0000520	Proptosis
HP:0000612	Iris coloboma
HP:0000684	Delayed eruption of teeth
HP:0000822	Hypertension
HP:0000916	Broad clavicles
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001007	Hirsutism
HP:0001034	Hypermelanotic macule
HP:0001059	Pterygium
HP:0001072	Thickened skin
HP:0001085	Papilledema
HP:0001171	Split hand
HP:0001220	Interphalangeal joint contracture of finger
HP:0001230	Broad metacarpals
HP:0001239	Wrist flexion contracture
HP:0001249	Intellectual disability
HP:0001288	Gait disturbance
HP:0001369	Arthritis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006979_675	Heel bone mineral density	5.000000e-26
GCST007623_1	Lack of premeditation	8.000000e-07
GCST010002_112	Refractive error	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0006946	behavioural disinhibition measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2095216 (PROTEIN FAMILY), CHEMBL2111321 (SELECTIVITY GROUP), CHEMBL333 (SINGLE PROTEIN), CHEMBL3885505 (PROTEIN FAMILY), CHEMBL4523970 (SELECTIVITY GROUP), CHEMBL4523971 (SELECTIVITY GROUP), CHEMBL4523972 (SELECTIVITY GROUP), CHEMBL4523984 (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: 1,007,846 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200699	DOXYCYCLINE	4	93,821
CHEMBL1350	TILUDRONIC ACID	4	14,784
CHEMBL178	DAUNORUBICIN	4	203,756
CHEMBL4303669	ZOLEDRONIC ACID	4	523
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL180570	MEDRONIC ACID	3	33,917
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL50	QUERCETIN	3	74,559
CHEMBL502620	ACLARUBICIN	3	30,150
CHEMBL75094	PRINOMASTAT	3	8,839
CHEMBL115653	CIPEMASTAT	2	359
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL2103847	TOSEDOSTAT	2	328
CHEMBL2107228	SOLIMASTAT	2	104
CHEMBL261932	TANOMASTAT	2	1,980
CHEMBL279786	BATIMASTAT	2	21,247
CHEMBL29292	UBENIMEX	2
CHEMBL440498	CTS-1027	2
CHEMBL4650334	ALDUMASTAT	2
CHEMBL76222	REBIMASTAT	2
CHEMBL297792	S-3304	1
CHEMBL4859268	AGG-523	1

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
MMP2 SERUM LEVELS	Bevacizumab	Inflammatory Breast Carcinoma	Sensitivity/Response	CIViC B	EID1156
MMP2 SERUM LEVELS	Bevacizumab	Brain Glioma	Sensitivity/Response	CIViC B	EID1158

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs243865	MMP2		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 (9 total), top 9:

Ligand	Action	Affinity	Parameter
ilomastat	Inhibition	9.72	pIC50
TP0556351	Inhibition	9.7	pIC50
AZD6605	Inhibition	8.52	pIC50
marimastat	Inhibition	8.22	pIC50
tanomastat	Inhibition	8.0	pKi
SB-3CT	Inhibition	7.86	pKi
CGS-27023A	Inhibition	7.6	pIC50
(R)-ND-336	Inhibition	6.9	pKi
tiludronic acid	Inhibition	5.14	pIC50

Binding affinities (BindingDB)

470 measured of 845 human assays (846 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-2-methyl-2-[(4-phenoxybenzene)sulfonyl]propanamide	KI	0.1 nM
N-Hydroxy-4-{[4-(phenoxyphenyl]sulfonyl}-1- (2-propynyl)4-piperidinecarboxamide, Monohydrochloride	KI	0.13 nM
N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}-1-(prop-2-en-1-yl)piperidine-4-carboxamide hydrochloride	KI	0.15 nM
tert-Butyl 4-[(Hydroxyamino)carbonyl]-4-{[(4-phenoxyphenyl)sulfonyl]methyl}piperidine-1-carboxylate	KI	0.2 nM
N-hydroxy-1-[(3-methoxyphenyl)methyl]-4-{[(4-phenoxybenzene)sulfonyl]methyl}piperidine-4-carboxamide hydrochloride	KI	0.2 nM
tert-butyl 4-(hydroxycarbamoyl)-4-[(4-phenoxybenzene)sulfonyl]piperidine-1-carboxylate	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
Vinylsulfone, 7	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
1-ethyl-N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide hydrochloride	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
(2R)-N-hydroxy-3-methyl-2-[(4-phenoxybenzene)sulfonamido]butanamide	IC50	1 nM
N-hydroxy-2-{(2-nitrophenyl)methylsulfonamido}acetamide	KI	1.4 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}propanamide	KI	1.4 nM
2-[benzyl(2,3,4,5,6-pentafluorobenzene)sulfonamido]-N-hydroxyacetamide	KI	1.5 nM
N-hydroxy-2-{(4-nitrophenyl)methylsulfonamido}acetamide	KI	1.5 nM
2-{(2-chlorophenyl)methylsulfonamido}-N-hydroxypropanamide	KI	1.5 nM
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-4-methylpentanamide	KI	1.9 nM
N-hydroxy-1-methanesulfonyl-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	2 nM
5-[3-[4-(4-chloro-3,5-difluorophenyl)piperazin-1-yl]-2-methyl-3-oxopropyl]-5-(methoxymethyl)imidazolidine-2,4-dione	IC50	2 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
2-[benzyl(1,1,2,2,3,3,4,4,4-nonafluorobutane)sulfonamido]-N-hydroxy-3-methylbutanamide	KI	2.4 nM
N-hydroxy-2-[(4-phenoxybenzene)sulfonyl]acetamide	KI	2.6 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
(2R)-2-{[4-(4-bromophenyl)benzene]sulfonamido}-N-hydroxy-3-methylbutanamide	IC50	3 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

ChEMBL bioactivities

4181 potent at pChembl≥5 of 4773 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL308533
11.00	Ki	0.01	nM	CHEMBL74040
11.00	Ki	0.01	nM	CHEMBL264859
11.00	Ki	0.01	nM	CHEMBL76158
11.00	Ki	0.01	nM	CHEMBL306033
11.00	Ki	0.01	nM	CHEMBL306947
11.00	Ki	0.01	nM	CHEMBL91655
11.00	Ki	0.01	nM	CHEMBL92453
11.00	Ki	0.01	nM	CHEMBL92828
11.00	Ki	0.01	nM	CHEMBL93395
11.00	Ki	0.01	nM	CHEMBL93583
11.00	Ki	0.01	nM	CHEMBL328092
10.70	Ki	0.02	nM	CHEMBL306608
10.70	Ki	0.02	nM	CHEMBL77663
10.70	Ki	0.02	nM	CHEMBL77057
10.70	Ki	0.02	nM	CHEMBL94114
10.70	Ki	0.02	nM	CHEMBL93791
10.70	Ki	0.02	nM	CHEMBL93235
10.54	IC50	0.029	nM	CTS-1027
10.52	Ki	0.03	nM	CHEMBL311397
10.52	Ki	0.03	nM	CHEMBL74308
10.52	Ki	0.03	nM	CHEMBL422058
10.52	Ki	0.03	nM	PRINOMASTAT
10.52	Ki	0.03	nM	CHEMBL93695
10.52	Ki	0.03	nM	CHEMBL92600
10.47	Ki	0.034	nM	CHEMBL5412341
10.47	IC50	0.034	nM	CHEMBL5412341
10.40	IC50	0.04	nM	CHEMBL330028
10.40	IC50	0.04	nM	CHEMBL198778
10.36	Ki	0.044	nM	CHEMBL4746390
10.36	IC50	0.044	nM	CHEMBL5209489
10.35	IC50	0.0449	nM	CHEMBL5288452
10.34	IC50	0.046	nM	CHEMBL5203315
10.32	IC50	0.048	nM	PRINOMASTAT
10.32	IC50	0.048	nM	CHEMBL4522121
10.32	IC50	0.048	nM	CHEMBL318484
10.30	Ki	0.05	nM	CHEMBL77659
10.30	IC50	0.05	nM	CHEMBL473539
10.30	Ki	0.05	nM	PRINOMASTAT
10.30	Ki	0.05	nM	CHEMBL327472
10.29	IC50	0.051	nM	CHEMBL5207094
10.26	IC50	0.055	nM	CHEMBL5183245
10.26	IC50	0.055	nM	CHEMBL5182207
10.22	Ki	0.06	nM	CHEMBL308511
10.22	Ki	0.06	nM	CHEMBL310037
10.22	Ki	0.06	nM	CHEMBL75403
10.22	IC50	0.06	nM	CHEMBL126461
10.21	Ki	0.062	nM	CHEMBL75403
10.19	IC50	0.065	nM	CHEMBL5280430
10.18	IC50	0.066	nM	CHEMBL5191373

PubChem BioAssay actives

3703 with measured affinity, of 6100 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
benzyl N-[[4-[[4-[(2R)-2-(hydroxycarbamoyl)cyclopentyl]sulfonylphenyl]carbamoyl]phenyl]methyl]carbamate	1594391: Inhibition of MMP2 (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
benzyl N-[4-[[4-[(2R)-2-(hydroxycarbamoyl)pyrrolidin-1-yl]sulfonylphenyl]carbamoyl]phenyl]carbamate	1731965: Inhibition of MMP2 (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
(2R)-5-[(2S,4S)-4-amino-2-[[(2S)-1-[[(2S)-1-[(5-amino-5-oxopentyl)amino]-4-carboxy-1-oxobutan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-[[4-[(4-carbamoylbenzoyl)amino]phenyl]sulfonylamino]-5-oxopentanoic acid	1965795: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-N2 as substrate preincubated for 10 to 15 mins followed by substrate addition and measured after 60 to 120 mins by fluorescence based assay	ki	<0.0001	uM
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	<0.0001	uM
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-4-methylsulfanyl-1-oxobutan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	<0.0001	uM
(2S)-3-methyl-2-[[4-[5-(5-methylthiophen-2-yl)-1,2-oxazol-3-yl]phenyl]sulfonylamino]butanoic acid	1937789: Inhibition of MMP2 (unknown origin)	ic50	<0.0001	uM
3-methyl-2-[(4-phenylphenyl)sulfonylamino]butanoic acid	732015: Inhibition of MMP2 (unknown origin)	ic50	<0.0001	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162785: Inhibition of human recombinant MMP2 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
(2R)-2-[3-(4-chlorophenyl)propyl]-N-[(2S)-3-cyclohexyl-1-[[3-[2-(morpholin-4-ylsulfonylamino)ethylamino]-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxybutanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-N-[(2S)-3-cyclohexyl-1-[[3-[2-(morpholin-4-ylsulfonylamino)ethylamino]-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxy-2-[3-(4-methylphenyl)propyl]butanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-2-[3-(4-chlorophenyl)propyl]-N-[(2S)-3-cyclohexyl-1-oxo-1-[[3-oxo-3-[2-(4-sulfamoylphenyl)ethylamino]propyl]amino]propan-2-yl]-N’-hydroxybutanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
3-[3-[[(2S)-2-[[(2R)-5-(4-chlorophenyl)-2-[2-(hydroxyamino)-2-oxoethyl]pentanoyl]amino]-3-cyclohexylpropanoyl]amino]propanoylamino]propanoic acid	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-N-[(2S)-3-cyclohexyl-1-[[3-(4-morpholin-4-ylbutylamino)-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxy-2-[3-(4-methylphenyl)propyl]butanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-2-[3-(4-chlorophenyl)propyl]-N-[(2S)-3-cyclohexyl-1-[[3-(4-morpholin-4-ylbutylamino)-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxybutanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-N-[(2S)-3-cyclohexyl-1-[[3-(2-morpholin-4-ylethylamino)-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxy-2-[3-(4-methylphenyl)propyl]butanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
methyl 3-[3-[[(2S)-2-[[(2R)-5-(4-chlorophenyl)-2-[2-(hydroxyamino)-2-oxoethyl]pentanoyl]amino]-3-cyclohexylpropanoyl]amino]propanoylamino]propanoate	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-N-[(2S)-3-cyclohexyl-1-oxo-1-[[3-oxo-3-[2-(4-sulfamoylphenyl)ethylamino]propyl]amino]propan-2-yl]-N’-hydroxy-2-[3-(4-methylphenyl)propyl]butanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	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	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(2R)-N-[(2S)-3-cyclohexyl-1-[[3-[4-(dimethylamino)butylamino]-3-oxopropyl]amino]-1-oxopropan-2-yl]-N’-hydroxy-2-[3-(4-methylphenyl)propyl]butanediamide	107321: Inhibitory constant against matrix metalloprotease-2	ki	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-3-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	107339: Inhibitory concentration against Matrix metalloprotease-2	ic50	<0.0001	uM
N-hydroxy-2-[(4-phenoxyphenyl)sulfonylamino]acetamide	736085: Inhibition of human recombinant MMP2 using Mca-Lys-Pro- Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate incubated for 2 hrs prior to substrate addition measured every 15 secs for 15 mins by fluorometric analysis	ic50	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	107333: In vitro selective inhibition against matrix metalloprotease-2 (MMP-2) using fluorimetric assay	ic50	<0.0001	uM
N-hydroxy-2-[(4-phenoxyphenyl)sulfonylmethyl]-1-prop-2-ynylpyrrolidine-2-carboxamide	107160: Inhibitory activity against human Matrix metalloprotease-2	ic50	0.0001	uM
N-hydroxy-1-(pyridin-3-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604449: Inhibition of human MMP2 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
N-[1-(dimethylsulfamoyl)-3-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpropan-2-yl]-N-hydroxyformamide	107333: In vitro selective inhibition against matrix metalloprotease-2 (MMP-2) using fluorimetric assay	ic50	0.0001	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	104710: Inhibition of fibroblast gelatinase A (MMP-2)	ic50	0.0001	uM
(2R)-N-hydroxy-3-methyl-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]butanamide	241639: Inhibition of human matrix metalloprotease-2	ic50	0.0001	uM
1-(cyclopropylmethyl)-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	0.0001	uM
N-hydroxy-2-methyl-2-(4-phenoxyphenyl)sulfonylpropanamide	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	0.0001	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	0.0001	uM
N-hydroxy-4-(4-phenylsulfanylphenyl)sulfonyl-1-prop-2-enylpiperidine-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	0.0001	uM
N-hydroxy-4-(4-phenoxyphenyl)sulfonyl-1-prop-2-ynylpiperidine-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	0.0001	uM
N-hydroxy-1-methyl-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	0.0001	uM
1-acetyl-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	0.0001	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107164: Inhibition of human matrix metalloprotease-2	ic50	0.0001	uM
N-[4-[(2R)-2-(hydroxycarbamoyl)cyclopentyl]sulfonylphenyl]-4-nitrobenzamide	1594391: Inhibition of MMP2 (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
(2R)-N-hydroxy-1-[4-[(4-nitrobenzoyl)amino]phenyl]sulfonylpyrrolidine-2-carboxamide	1731965: Inhibition of MMP2 (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
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-3-[[(2S)-4-amino-4-oxo-2-[5-(4-phenoxyphenyl)sulfonylpentanoylamino]butanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-4-methylsulfanyl-1-oxobutan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[4-[[4-(4-fluorophenoxy)benzoyl]amino]butanoylamino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]butanoyl]amino]-4-methylpentanoyl]-methylamino]-5-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-5-oxopentanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-3-carboxypropanoyl]amino]butanoyl]amino]-4-methylpentanoyl]-methylamino]-5-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-5-oxopentanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-4-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxobutan-2-yl]amino]-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(3S)-4-[[(2S)-3-amino-1-[[(2S)-1-[[(2S,3S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-4-amino-4-oxo-2-[4-[(4-phenoxyphenyl)sulfonylamino]butanoylamino]butanoyl]amino]-4-oxobutanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[6-[[4-(4-carbamoylphenoxy)benzoyl]amino]hexanoylamino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]butanoyl]amino]-4-methylpentanoyl]-methylamino]-5-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-5-oxopentanoic acid	1912253: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases activity, decreases secretion, increases secretion, affects reaction, decreases expression (+7 more)	21
bisphenol A	increases activity, increases expression, affects cotreatment, decreases methylation, decreases activity (+3 more)	17
Arsenic Trioxide	increases activity, affects cotreatment, decreases expression, decreases secretion, decreases reaction (+5 more)	17
Cadmium Chloride	increases abundance, increases expression, increases reaction, decreases expression, increases secretion (+3 more)	15
sodium arsenite	decreases expression, increases reaction, decreases reaction, increases expression, increases activity (+2 more)	14
Plant Extracts	increases reaction, increases expression, decreases expression, affects reaction, decreases reaction (+3 more)	13
Cadmium	increases abundance, increases reaction, affects expression, affects reaction, increases expression (+3 more)	11
Tetradecanoylphorbol Acetate	increases secretion, decreases reaction, increases activity, increases expression	11
U 0126	decreases expression, increases reaction, decreases reaction, increases expression, decreases activity (+2 more)	10
Estradiol	increases activity, affects expression, affects cotreatment, increases reaction, decreases reaction (+4 more)	10
SB 203580	increases expression, increases activity, decreases activity, decreases expression, increases reaction (+2 more)	9
Oxygen	increases expression, increases activity, decreases expression, increases reaction, affects cotreatment (+2 more)	9
diallyl trisulfide	decreases activity, decreases expression, decreases reaction, increases reaction	8
Cisplatin	affects cotreatment, decreases expression, decreases activity, affects expression, increases expression (+3 more)	8
Quercetin	decreases activity, affects activity, affects expression, increases expression, increases secretion (+7 more)	8
Particulate Matter	increases expression, decreases reaction, increases activity, increases reaction, decreases expression (+1 more)	8
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases expression, increases secretion, decreases expression (+1 more)	7
Curcumin	decreases reaction, increases expression, increases activity, decreases activity, decreases expression (+2 more)	7
Lipopolysaccharides	decreases expression, increases activity, decreases reaction, increases expression, increases reaction (+1 more)	7
perfluorooctanoic acid	decreases reaction, increases activity, increases expression, affects cotreatment, decreases expression	6
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases activity, decreases expression, decreases reaction, increases activity, increases expression	6
pyrazolanthrone	increases activity, increases expression, increases reaction, decreases activity, decreases expression (+1 more)	6
Fulvestrant	affects cotreatment, decreases reaction, increases expression, decreases methylation, decreases expression	6
Benzo(a)pyrene	affects reaction, decreases expression, increases expression, increases methylation, affects expression (+1 more)	6
Doxorubicin	decreases response to substance, affects expression, affects cotreatment, decreases expression, affects response to substance (+5 more)	6
Arsenic	affects cotreatment, increases secretion, increases expression, decreases reaction, decreases expression (+1 more)	5
Dexamethasone	affects reaction, decreases reaction, increases expression, increases activity, decreases expression (+2 more)	5
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects reaction, increases activity, affects expression	5
Tobacco Smoke Pollution	increases activity, increases expression, decreases expression, decreases secretion, decreases reaction	5
Tretinoin	increases activity, increases expression, decreases activity, decreases expression, decreases reaction	5

ChEMBL screening assays

771 unique, capped per target: 735 binding, 28 admet, 7 functional, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4481593	Binding	Inhibition of collagenase (unknown origin) at 200 uM relative to control	Deleting a Chromatin Remodeling Gene Increases the Diversity of Secondary Metabolites Produced by Colletotrichum higginsianum. — J Nat Prod
CHEMBL663111	Functional	In vitro antagonist activity against collagenase induced gel-filtered platelet (GFP) aggregation at 50 uM; NA=Inactive	Discovery and optimization of a novel series of thrombin receptor (par-1) antagonists: potent, selective peptide mimetics based on indole and indazole templates. — J Med Chem
CHEMBL4000925	ADMET	Inhibition of APMA-activated recombinant human MMP-2 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: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8KN	Abcam HCT 116 MMP2 KO	Cancer cell line	Male
CVCL_B8YZ	Abcam MCF-7 MMP2 KO	Cancer cell line	Female
CVCL_B9MW	Abcam A-549 MMP2 KO	Cancer cell line	Male
CVCL_E0I8	Ubigene HeLa MMP2 KO	Cancer cell line	Female
CVCL_E2CL	HAP1 MMP2 (-) 2	Cancer cell line	Male
CVCL_XQ58	HAP1 MMP2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01418118	PHASE4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT03017053	PHASE4	UNKNOWN	The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor
NCT03684707	PHASE4	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00158652	PHASE3	COMPLETED	Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC
NCT00158678	PHASE3	COMPLETED	IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC
NCT00402779	PHASE3	COMPLETED	Erlotinib Prevention of Oral Cancer (EPOC)
NCT00655421	PHASE3	UNKNOWN	Oral Cancer Screening in Mumbai, India by Primary Health Care Workers
NCT00750503	PHASE3	COMPLETED	Workplace Tobacco Cessation And Oral Cancer Screening Study
NCT00964977	PHASE3	COMPLETED	Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis.
NCT01039298	PHASE3	UNKNOWN	Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL
NCT03685409	PHASE3	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions
NCT05721755	PHASE3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT06589804	PHASE3	RECRUITING	Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
NCT06737822	PHASE3	RECRUITING	Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:
NCT07402538	PHASE3	NOT_YET_RECRUITING	Surgery With or Without Neoadjuvant Treatment of SBRT Plus Chemoimmunotherapy in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma
NCT07441681	PHASE3	NOT_YET_RECRUITING	Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00330382	PHASE2	COMPLETED	Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
NCT00400205	PHASE2	TERMINATED	Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil
NCT00933387	PHASE2	COMPLETED	A Study of Neoadjuvant Bio-C/T Followed by Concurrent Bio-R/T in High-risk Locally Advanced Oral Squamous Cell Carcinoma
NCT01440270	PHASE2	COMPLETED	Neo-adjuvant Erbitux-based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer
NCT01733797	PHASE2	COMPLETED	Trismus Trial of Therabite vs Wooden Spatula in Head and Neck Cancer Patients
NCT02734537	PHASE2	RECRUITING	Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
NCT02960724	PHASE2	UNKNOWN	uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer
NCT03008694	PHASE2	UNKNOWN	Effect of FDG-PET/CT for Simulation and Radiation Treatment Planning in Oral Cancer Patients
NCT03174275	PHASE2	ACTIVE_NOT_RECRUITING	Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma
NCT03383094	PHASE2	ACTIVE_NOT_RECRUITING	Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
NCT03529422	PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN
NCT04191460	PHASE2	RECRUITING	Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer
NCT04251949	PHASE2	COMPLETED	Evaluation of the Photobiomodulation Using LED Lamp for Curative Treatment of Radio-induced Mucositis.
NCT04541355	PHASE2	COMPLETED	Sodium Thiosulfate in Preventing Ototoxicity for Squamous Cell Cancer Patients Undergoing Chemoradiation With Cisplatin
NCT04862650	PHASE2	ACTIVE_NOT_RECRUITING	Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck