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): 467 total — 22 pathogenic, 10 likely-pathogenic (top 7% of genes corpus-wide)
• GTEx eGene: eQTL in 4 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 87
• Drug target: yes — 3 curated mechanism-of-action drugs; 26 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.65 (unconstrained)
• MANE Select transcript: NM_004530
• Interaction hub: 4,494 STRING partners (top 1% of genes corpus-wide)

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: 22 — 16 protein_coding, 6 nonsense_mediated_decay

MANE Select: ENST00000219070

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000219070, ENST00000437642, ENST00000543485, ENST00000564864, ENST00000566564, ENST00000568715, ENST00000570283, ENST00000570308, ENST00001050250, ENST00001050251, ENST00001050253, ENST00001050254, ENST00001050255, ENST00001050256, ENST00001050258, ENST00001050259, ENST00001050260, ENST00001050261, ENST00001050262, ENST00001063437, ENST00001111701, ENST00001132460

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.

Highest expression (Bgee): stromal cell of endometrium, gall bladder, mucosa of stomach, endocervix, skin of hip.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MMP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	1.5e-12	+0.41	16:55466308:A:G
Skin Not Sun Exposed Suprapubic	sqtl	6.9e-06	-0.42	16:55457137:C:A
Skin Sun Exposed Lower leg	sqtl	1.1e-05	+0.29	16:55467761:G:A
Brain Cerebellum	eqtl	1.7e-02	+0.68	16:55608349:G:A
Colon Sigmoid	eqtl	3.3e-02	-0.15	16:55560899:T:C
Artery Tibial	eqtl	3.4e-02	-0.19	16:55320412:G:C
Adrenal Gland	eqtl	3.8e-02	-0.65	16:56309042:T:C
Esophagus Gastroesophageal Junction	sqtl	4.1e-02	-1.42	16:54669330:A:T

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

showing 100 of 289 tissues 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
left coronary artery	UBERON:0001626	98.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.46	gold quality
myometrium	UBERON:0001296	98.45	gold quality
skin of abdomen	UBERON:0001416	98.41	gold quality
urinary bladder	UBERON:0001255	98.39	gold quality
zone of skin	UBERON:0000014	98.26	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.23	gold quality
aorta	UBERON:0000947	98.09	gold quality
right atrium auricular region	UBERON:0006631	98.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.02	gold quality
lower esophagus	UBERON:0013473	97.99	gold quality
cardiac atrium	UBERON:0002081	97.82	gold quality
adipose tissue	UBERON:0001013	97.80	gold quality
nerve	UBERON:0001021	97.75	gold quality
tibial nerve	UBERON:0001323	97.75	gold quality
urethra	UBERON:0000057	97.72	gold quality
calcaneal tendon	UBERON:0003701	97.72	gold quality
rectum	UBERON:0001052	97.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.68	gold quality
apex of heart	UBERON:0002098	97.64	gold quality
lower lobe of lung	UBERON:0008949	97.56	gold quality
connective tissue	UBERON:0002384	97.54	gold quality
right lobe of thyroid gland	UBERON:0001119	97.51	gold quality
tibial artery	UBERON:0007610	97.46	gold quality
fundus of stomach	UBERON:0001160	97.45	gold quality
popliteal artery	UBERON:0002250	97.45	gold quality
pericardium	UBERON:0002407	97.39	gold quality
caecum	UBERON:0001153	97.36	gold quality
minor salivary gland	UBERON:0001830	97.35	gold quality
corpus epididymis	UBERON:0004359	97.35	gold quality
ovary	UBERON:0000992	97.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.30	gold quality
vena cava	UBERON:0004087	97.28	gold quality
mammalian vulva	UBERON:0000997	97.21	gold quality
caput epididymis	UBERON:0004358	97.10	gold quality
nipple	UBERON:0002030	97.09	gold quality
transverse colon	UBERON:0001157	97.05	gold quality
vagina	UBERON:0000996	97.00	gold quality
vermiform appendix	UBERON:0001154	96.95	gold quality
vein	UBERON:0001638	96.95	gold quality
pylorus	UBERON:0001166	96.93	gold quality
superficial temporal artery	UBERON:0001614	96.93	gold quality
layer of synovial tissue	UBERON:0007616	96.89	gold quality
saphenous vein	UBERON:0007318	96.84	gold quality
mammary duct	UBERON:0001765	96.82	gold quality
small intestine	UBERON:0002108	96.77	gold quality
stomach	UBERON:0000945	96.73	gold quality
left lobe of thyroid gland	UBERON:0001120	96.67	gold quality
lung	UBERON:0002048	96.48	gold quality
body of stomach	UBERON:0001161	96.47	gold quality
heart	UBERON:0000948	96.42	gold quality
tendon	UBERON:0000043	96.11	gold quality
mucosa of transverse colon	UBERON:0004991	96.11	gold quality
thyroid gland	UBERON:0002046	96.09	gold quality
epididymis	UBERON:0001301	95.93	gold quality
metanephros cortex	UBERON:0010533	95.92	gold quality
mucosa of urinary bladder	UBERON:0001259	95.89	gold quality
heart left ventricle	UBERON:0002084	95.69	gold quality
thoracic mammary gland	UBERON:0005200	95.67	gold quality
cardiac ventricle	UBERON:0002082	95.58	gold quality
mammary gland	UBERON:0001911	95.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.55	gold quality
female reproductive system	UBERON:0000474	95.49	gold quality
esophagus	UBERON:0001043	95.49	gold quality
cardia of stomach	UBERON:0001162	95.48	gold quality
tibia	UBERON:0000979	95.42	gold quality
penis	UBERON:0000989	95.41	gold quality
intestine	UBERON:0000160	95.28	gold quality
left adrenal gland	UBERON:0001234	95.07	gold quality
left adrenal gland cortex	UBERON:0035825	94.95	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Gallbladder	tissue	994.4	not detected
Urinary bladder	tissue	617.6	medium
Smooth muscle	tissue	437.0	low
Cervix	tissue	425.2	low
Ovary	tissue	365.7	not detected
Endometrium 1	tissue	332.4	medium
Vagina	tissue	237.3	not detected
Placenta	tissue	210.8	high
Epididymis	tissue	181.5	not detected
Breast	tissue	176.0	not detected
Lung	tissue	173.4	medium
Adipose tissue	tissue	168.6	not detected
Rectum	tissue	160.3	not detected
Skin 1	tissue	159.4	not detected
Colon	tissue	142.1	low
Seminal vesicle	tissue	129.4
Appendix	tissue	127.3	not detected
Esophagus	tissue	114.0	not detected
Heart muscle	tissue	108.4	low
Prostate	tissue	96.1	low
Fallopian tube	tissue	94.3	medium
Spinal cord	tissue	86.3
Small intestine	tissue	81.9	not detected
Stomach 1	tissue	76.6	not detected
Adrenal gland	tissue	64.2	not detected
Tongue	tissue	61.6
Superior colliculi	tissue	56.6
Duodenum	tissue	54.1	not detected
Substantia nigra	tissue	50.2
Testis	tissue	46.3	low
Medulla oblongata	tissue	40.6
Pancreas	tissue	35.9	not detected
Midbrain	tissue	34.0
Corpus callosum	tissue	32.1
Skeletal muscle	tissue	31.8	not detected
Tonsil	tissue	28.3	not detected
Thalamus	tissue	27.7
Thyroid gland	tissue	27.2	not detected
Salivary gland	tissue	26.6	not detected
Spleen	tissue	26.5	low
Lymph node	tissue	26.2	not detected
Pons	tissue	26.0
Kidney	tissue	25.8	low
Hypothalamus	tissue	25.7
Hippocampal formation	tissue	21.1
Putamen	tissue	19.3
Periaqueductal gray	tissue	19.3
Thymus	tissue	18.5
Ventral forebrain	tissue	17.1
Choroid plexus	tissue	17.0
Septum	tissue	16.8
Amygdala	tissue	15.1
Cerebral cortex	tissue	14.8	low
Retrosplenial cortex	tissue	14.8
Entorhinal cortex	tissue	14.6
Liver	tissue	14.5	not detected
Motor cortex	tissue	14.4
Basal ganglia	tissue	14.2	not detected
Pituitary gland	tissue	14.1
Temporal cortex	tissue	13.9

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (288.9), Dorsal spinal cord (86.3), Ventral spinal cord (56.6), White matter (32.1), Ventral hippocampus (21.1).

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)

Targeting MMP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 95 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 6.48e-05, LOEUF 0.654, missense Z 1.43 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000219070 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
16:55,479,480–55,484,160	223 / 232.8	0.96	no
16:55,484,161–55,485,412	25 / 53.5	0.47	no
16:55,485,413–55,505,439	555 / 592.0	0.94	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97009) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 56 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body size	2
decreased angiogenesis	2
decreased bone mineral density	1
short mandible	1
short maxilla	1
abnormal trabecular bone morphology	1
abnormal angiogenesis	1
abnormal response to cardiac infarction	1
abnormal cranium morphology	1
short snout	1
abnormal stomach morphology	1
abnormal spleen morphology	1
enlarged spleen	1
enlarged lymph nodes	1
decreased body length	1
cataract	1
abnormal retina morphology	1
abnormal cardiovascular system physiology	1
postnatal growth retardation	1
abnormal inflammatory response	1
brain inflammation	1
decreased inflammatory response	1
abnormal seminal vesicle morphology	1
abnormal skin morphology	1
abnormal skeleton development	1

+31 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R543	98.1%	Diamond
Oryctolagus cuniculus	P50757	95.2%	Diamond
Bos taurus	Q9GLE5	95.1%	Diamond
Equus caballus	Q28377	94.4%	Diamond
Mesocricetus auratus	Q9ESM7	92.7%	Diamond
Notophthalmus viridescens	Q91400	91.7%	Diamond
Xenopus laevis	Q91740	91.7%	Diamond
Gallus gallus	P11722	88.9%	Diamond
Sus scrofa	P79287	88.8%	Diamond
Canis lupus familiaris	Q28275	84.7%	Diamond
Felis catus	P55032	72.5%	Diamond
Arabidopsis thaliana	Q5XF51	71.1%	Diamond
Paracentrotus lividus	P22757	70.4%	Diamond
Hemicentrotus pulcherrimus	P91953	70.4%	Diamond
Glycine max	P29136	48.7%	Diamond
Tannerella forsythia 92A2	D0EM77	45.2%	Diamond
Heliothis virescens ascovirus 3e	A4KX75	59.2%	Diamond
Spodoptera frugiperda ascovirus 1a	Q0E587	59.2%	Diamond
Invertebrate iridescent virus 6	O55761	46.9%	Diamond
Invertebrate iridescent virus 3	Q196W5	43.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MMP2-AS1	ncRNA	107984884
IRX6	protein-coding	79190
LPCAT2	protein-coding	54947
CAPNS2	protein-coding	84290
SLC6A2	protein-coding	6530

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 (144 total): strand 48, binding site 23, helix 20, turn 13, 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 by resolution:

PDB	Title	Method	Resolution (Å)
3AYU	Crystal structure of MMP-2 active site mutant in complex with APP-drived decapeptide …	X-RAY DIFFRACTION	2
7XJO	Crystal structure of human MMP-2 catalytic domain in complex with inhibitor	X-RAY DIFFRACTION	2
1GEN	C-TERMINAL DOMAIN OF GELATINASE A	X-RAY DIFFRACTION	2.15
8H78	Crystal structure of human MMP-2 catalytic domain in complex with inhibitor	X-RAY DIFFRACTION	2.4
1RTG	C-TERMINAL DOMAIN (HAEMOPEXIN-LIKE DOMAIN) OF HUMAN MATRIX METALLOPROTEINASE-2	X-RAY DIFFRACTION	2.6
1EAK	Catalytic domain of proMMP-2 E404Q mutant	X-RAY DIFFRACTION	2.66
1CK7	GELATINASE A (FULL-LENGTH)	X-RAY DIFFRACTION	2.8
1QIB	CRYSTAL STRUCTURE OF GELATINASE A CATALYTIC DOMAIN	X-RAY DIFFRACTION	2.8
7XGJ	Crystal structure of human MMP-2 catalytic domain in complex with inhibitor	X-RAY DIFFRACTION	2.8
1GXD	proMMP-2/TIMP-2 complex	X-RAY DIFFRACTION	3.1
1CXW	THE SECOND TYPE II MODULE FROM HUMAN MATRIX METALLOPROTEINASE 2	SOLUTION NMR
1HOV	SOLUTION STRUCTURE OF A CATALYTIC DOMAIN OF MMP-2 COMPLEXED WITH SC-74020	SOLUTION NMR
1J7M	The Third Fibronectin Type II Module from Human Matrix Metalloproteinase 2	SOLUTION NMR
1KS0	The First Fibronectin Type II Module from Human Matrix Metalloproteinase 2	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Metallopeptidases, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Mutational cancer driver genes, Candidate cardiovascular disease genes, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
404

Ligand- & substrate-binding residues (23)

Position	Role
102	Zn(2+)
134	Ca(2+)
168	Ca(2+)
178	Zn(2+)
180	Zn(2+)
185	Ca(2+)
186	Ca(2+)
193	Zn(2+)
200	Ca(2+)
202	Ca(2+)
204	Ca(2+)
206	Zn(2+)
208	Ca(2+)
209	Ca(2+)
211	Ca(2+)
403	Zn(2+)
407	Zn(2+)
413	Zn(2+)
476	Ca(2+)
521	Ca(2+)
569	Ca(2+)
618	Ca(2+)

Disulfide bonds (7)

Type	Positions
Disulfide bond	233–259, 247–274, 291–317, 305–332, 349–375, 363–390, 469–660

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	573, 642

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 20; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

20 pathways:

ID	Pathway	Evidence
R-HSA-1592389	Activation of Matrix Metalloproteinases	curated
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-5687128	MAPK6/MAPK4 signaling	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-422475	Axon guidance	—
R-HSA-1442490	Collagen degradation	electronic
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1474228	Degradation of the extracellular matrix	electronic
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-168256	Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-9675108	Nervous system development	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-9006931	Signaling by Nuclear Receptors	—

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 (45): angiogenesis (GO:0001525), ovarian follicle development (GO:0001541), ovulation from ovarian follicle (GO:0001542), luteinization (GO:0001553), response to hypoxia (GO:0001666), 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), 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), prostate gland epithelium morphogenesis (GO:0060740), trophoblast cell migration (GO:0061450), cellular response to interleukin-1 (GO:0071347), cellular response to estradiol stimulus (GO:0071392), cellular response to UV-A (GO:0071492), cellular response to fluid shear stress (GO:0071498), positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903378), response to amyloid-beta (GO:1904645), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), response to oxidative stress (GO:0006979), female pregnancy (GO:0007565), response to cytokine (GO:0034097), positive regulation of apoptotic process (GO:0043065), cellular response to cytokine stimulus (GO:0071345), negative regulation of metallopeptidase activity (GO:1905049)

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 (8): extracellular region (GO:0005576), 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

14 top-level categories:

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

53 GO namespaces:

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
animal gross anatomical part developmental process	1
ovulation	1
response to stress	1
response to decreased oxygen levels	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
catabolic process	1
collagen metabolic process	1
response to lipid	1
response to oxygen-containing compound	1
protein binding	1
metallopeptidase activity	1
serine-type peptidase activity	1
transition metal ion binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1
myofibril	1
external encapsulating structure	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 64 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration	BP	mutant phenotype
cellular response to UV-A	BP	direct assay
collagen catabolic process	BP	direct assay
endodermal cell differentiation	BP	expression pattern
positive regulation of vascular associated smooth muscle cell proliferation	BP	mutant phenotype
proteolysis	BP	direct assay
trophoblast cell migration	BP	direct assay
extracellular matrix	CC	direct assay
endopeptidase activity	MF	direct assay
metalloendopeptidase activity	MF	direct assay
metallopeptidase activity	MF	direct assay
serine-type endopeptidase activity	MF	experiment

Protein interactions and networks

STRING

showing 15 of 4,494 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP2	TIMP2	P16035	952
MMP2	TIMP1	P01033	929
MMP2	TGFB1	P01137	857
MMP2	AKT1	P31749	843
MMP2	TIMP3	P35625	830
MMP2	MMP14	P50281	827
MMP2	ELN	P15502	825
MMP2	TIMP4	Q99727	819
MMP2	FN1	P02751	812
MMP2	HPX	P02790	791
MMP2	CDH1	P12830	777
MMP2	RECK	O95980	759
MMP2	PIK3CG	P48736	758
MMP2	PIK3CD	O00329	757
MMP2	PIK3CB	P42338	757

IntAct

Human interaction partners of MMP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

21 partners by confidence:

Partner	Interaction type	MIscore	Records
COL5A1	physical association	0.780	2
TIMP2	direct interaction	0.690	1
COL4A1	association	0.640	1
APP	direct interaction	0.620	9
PCSK9	cleavage reaction	0.620	4
REL	physical association	0.560	3
SCUBE3	protein cleavage	0.440	2
LOX	direct interaction	0.440	1
PCOLCE	cleavage reaction	0.440	1
ANXA2	association	0.430	12
HSP90AA1	physical association	0.400	1
LDLR	physical association	0.400	1
COL2A1	association	0.350	1
PLOD3	association	0.350	1
A2M	proximity	0.270	1
BACE1	proximity	0.270	1
TGFB1	proximity	0.270	1
MTNR1A	physical association	0.000	2
CAPN3	physical association	0.000	1
DISC1	physical association	0.000	1
MTNR1B	physical association	0.000	1

BioGRID (108 interactions; top human partners by supporting records): TIMP2 (Affinity Capture-MS; 9 records), CCL7 (Two-hybrid; 4 records), ITGAV (Affinity Capture-Western; 4 records), PAK4 (Affinity Capture-Western; 4 records), ITGB1 (Affinity Capture-Western; 3 records), TIMP3 (Affinity Capture-MS; 3 records), A2M (Co-localization; 2 records), COL12A1 (Affinity Capture-MS; 2 records), COL14A1 (Affinity Capture-MS; 2 records), COL18A1 (Affinity Capture-MS; 2 records), COL2A1 (Affinity Capture-MS; 2 records), COL4A1 (Affinity Capture-MS; 2 records), COL4A2 (Affinity Capture-MS; 2 records), COL5A1 (Affinity Capture-MS; 2 records), COL6A1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 20 of 24 signaling 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”
HIF1A	“up-regulates quantity by expression”	MMP2	“transcriptional regulation”
MMP2	up-regulates	Epithelial-mesenchymal_transition
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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
MMP2-MMP14-TIMP2 complex	3	TIMP2, MMP14, MMP2
ANXA2-MMP2-WFDC2 complex	3	WFDC2, ANXA2, MMP2
CLDN1-MMP2 complex	2	CLDN1, MMP2
★ HDAC10-MMP2 complex	2	HDAC10, MMP2

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ITGAV;ITGB3	ligand

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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	5	42.6×	2e-05
ECM proteoglycans	5	37.6×	2e-05
Extracellular matrix organization	6	18.9×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	6	64.2×	2e-07

Disease & clinical

Genetic variants

Variant evidence for MMP2: 467 ClinVar records (32 pathogenic / likely pathogenic); 1 CIViC cancer variant; 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	10
Uncertain significance	185
Likely benign	132
Benign	61

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 32 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
17109	NM_004530.6(MMP2):c.732C>A (p.Tyr244Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
198809	NM_004530.6(MMP2):c.1287del (p.Asn430fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1341994	NM_004530.6(MMP2):c.301C>T (p.Arg101Cys)	Pathogenic	criteria provided, single submitter	2
195227	NM_004530.6(MMP2):c.265del (p.Asp90fs)	Pathogenic	criteria provided, single submitter	1
915430	NM_004530.6(MMP2):c.1648C>T (p.Arg550Ter)	Pathogenic	criteria provided, single submitter	1
1323283	NM_004530.6(MMP2):c.1289del (p.Asn430fs)	Pathogenic	criteria provided, single submitter	1
1332689	NM_004530.6(MMP2):c.910_916del (p.Ser304fs)	Pathogenic	criteria provided, single submitter	1
1332865	NM_004530.6(MMP2):c.789C>A (p.Tyr263Ter)	Pathogenic	criteria provided, single submitter	1
1335213	NM_004530.6(MMP2):c.865C>T (p.Gln289Ter)	Pathogenic	criteria provided, single submitter	1
1685950	NM_004530.6(MMP2):c.691G>T (p.Glu231Ter)	Pathogenic	criteria provided, single submitter	1
2031305	NM_004530.6(MMP2):c.1743_1744dup (p.Ile582fs)	Pathogenic	criteria provided, single submitter	1
3003362	NM_004530.6(MMP2):c.1081G>T (p.Glu361Ter)	Pathogenic	criteria provided, single submitter	1
3615226	NM_004530.6(MMP2):c.481C>T (p.Arg161Ter)	Pathogenic	criteria provided, single submitter	1
3678169	NM_004530.6(MMP2):c.1160G>A (p.Trp387Ter)	Pathogenic	criteria provided, single submitter	1
3777151	NM_004530.6(MMP2):c.348del (p.Lys116fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore MMP2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,039):

Position(s)	Effect	Δscore	Sites
16:55479633–55479634	donor_loss	1.0000	5
16:55482899	acceptor_gain	1.0000
16:55482907–55482908	acceptor_loss	1.0000	6
16:55483136	donor_loss	1.0000
16:55485297–55485298	acceptor_loss	1.0000	6
16:55485428–55485429	donor_loss	1.0000	4
16:55485602–55485603	acceptor_loss	1.0000	3
16:55485752	donor_gain	1.0000
16:55485778–55485779	donor_loss	1.0000	5
16:55488536	acceptor_gain	1.0000

AlphaMissense

2,002 missense substitutions predicted likely pathogenic (of 4,389 scored), across 445 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M421	9	0.985	0.999
M77	9	0.922	0.995
M97	9	0.843	0.998
H193	8	0.999	1.000
D208	8	0.999	1.000
H178	8	0.998	0.999
H206	8	0.998	0.999
H403	8	0.998	0.999
H407	8	0.998	0.999
H413	8	0.998	0.999
D180	8	0.997	0.999
F184	8	0.997	1.000
D204	8	0.995	0.999
D437	8	0.995	0.999
F207	8	0.993	1.000
D106	8	0.992	0.998
F173	8	0.991	0.999
D185	8	0.986	0.998
F113	8	0.978	0.999
F405	8	0.973	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
multicentric osteolysis, nodulosis, and arthropathy	Strong	Autosomal recessive	3
multicentric osteolysis-nodulosis-arthropathy spectrum	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Paediatric disorders	green
Skeletal dysplasia	green
Fetal anomalies	amber

Mondo (2): multicentric osteolysis-nodulosis-arthropathy spectrum (MONDO:0018298), multicentric osteolysis, nodulosis, and arthropathy (MONDO:0009809)

Orphanet (2): Torg-Winchester syndrome (Orphanet:3460), Multicentric osteolysis-nodulosis-arthropathy spectrum (Orphanet:371428)

HPO phenotypes

showing 60 of 87 phenotypes (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 clavicle
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
HP:0001473	Metatarsal osteolysis
HP:0001476	Delayed closure of the anterior fontanelle
HP:0001482	Subcutaneous nodule
HP:0001495	Carpal osteolysis
HP:0001504	Metacarpal osteolysis
HP:0001539	Omphalocele
HP:0001626	Abnormality of the cardiovascular system
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001634	Mitral valve prolapse
HP:0001647	Bicuspid aortic valve
HP:0001678	Atrioventricular block
HP:0001680	Coarctation of aorta
HP:0001719	Double outlet right ventricle
HP:0001761	Pes cavus
HP:0001763	Pes planus
HP:0001783	Broad metatarsal
HP:0001836	Camptodactyly of toe
HP:0001999	Abnormal facial shape
HP:0002007	Frontal bossing
HP:0002659	Increased susceptibility to fractures
HP:0002751	Kyphoscoliosis
HP:0002753	Thin bony cortex
HP:0002797	Osteolysis
HP:0002829	Arthralgia
HP:0002953	Vertebral compression fracture
HP:0003016	Metaphyseal widening
HP:0003040	Arthropathy
HP:0003179	Protrusio acetabuli
HP:0003273	Hip contracture

GWAS associations

3 associations:

Study	Trait	p-value
GCST006979_675	Heel bone mineral density	5e-26
GCST010002_164	Refractive error	7e-10
GCST007623_3	Lack of premeditation	8e-7

EFO canonical traits (from GWAS)

2 canonical traits:

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

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MMP2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
MARIMASTAT	Small molecule	3
CTS-1027	Small molecule	2
REBIMASTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,017,249 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

26 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL790	CHLORHEXIDINE	4	85,849
CHEMBL178	DAUNORUBICIN	4	205,873
CHEMBL53463	DOXORUBICIN	4	317,622
CHEMBL1200699	DOXYCYCLINE	4	94,976
CHEMBL1350	TILUDRONIC ACID	4	14,868
CHEMBL4303669	ZOLEDRONIC ACID	4	528
CHEMBL279785	MARIMASTAT	3	29,705
CHEMBL502620	ACLARUBICIN	3	30,484
CHEMBL145	CAFFEIC ACID	3	36,727
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	23,201
CHEMBL180570	MEDRONIC ACID	3	33,980
CHEMBL75094	PRINOMASTAT	3	8,942
CHEMBL50	QUERCETIN	3	75,572
CHEMBL440498	CTS-1027	2	651
CHEMBL76222	REBIMASTAT	2	363
CHEMBL4650334	ALDUMASTAT	2	61
CHEMBL279786	BATIMASTAT	2	21,436
CHEMBL115653	CIPEMASTAT	2	380
CHEMBL19611	ILOMASTAT	2	12,186
CHEMBL151	LUTEOLIN	2	23,845
CHEMBL2107228	SOLIMASTAT	2
CHEMBL261932	TANOMASTAT	2
CHEMBL2103847	TOSEDOSTAT	2
CHEMBL29292	UBENIMEX	2
CHEMBL4859268	AGG-523	1
CHEMBL297792	S-3304	1

Clinical evidence (CIViC)

Drug × variant × indication, from 2 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

2 predictive associations by evidence level:

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

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

SERUM LEVELS.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs243865	ulinastatin	Efficacy	Allele T is associated with decreased response to ulinastatin in people with Pancreatitis as compared to allele C.	PMID:31192912

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)

4047 measured of 5085 human assays (5092 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2R)-2-{[4-(4-bromophenyl)benzene]sulfonamido}-3-methylbutanoic acid	IC50	0.004 nM
N*1*-(2-Cyclohexyl-1-{2-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
3-(3-{2-[5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionylamino)-propionic acid methyl ester	KI	0.01 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-(2-cyclohexyl-1-{2-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-succinamide	KI	0.01 nM
N*1*-(2-Cyclohexyl-1-{2-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
N*1*-{2-Cyclohexyl-1-[2-(2-morpholin-4-yl-ethylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
3-(3-{2-[5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionylamino)-propionic acid	KI	0.01 nM
3-{(S)-2-[(R)-5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionic acid	KI	0.01 nM
(R)-N*1*-{(S)-2-Cyclohexyl-1-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
(R)-N*1*-[(S)-2-Cyclohexyl-1-(2-morpholin-4-yl-ethylcarbamoyl)-ethyl]-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{(S)-2-cyclohexyl-1-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.01 nM
3-{(S)-2-[(R)-5-(4-Chloro-phenyl)-2-hydroxycarbamoylmethyl-pentanoylamino]-3-cyclohexyl-propionylamino}-propionic acid methyl ester	KI	0.01 nM
(R)-N*1*-{(S)-2-Cyclohexyl-1-[2-(morpholine-4-sulfonylamino)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.01 nM
N*1*-{2-Cyclohexyl-1-[2-(4-dimethylamino-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{2-cyclohexyl-1-[2-(3-morpholin-4-yl-3-oxo-propylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.02 nM
N*1*-{2-Cyclohexyl-1-[2-(4-morpholin-4-yl-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
(R)-N*1*-[(S)-2-Cyclohexyl-1-(4-morpholin-4-yl-butylcarbamoyl)-ethyl]-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-[(S)-2-cyclohexyl-1-(3-morpholin-4-yl-3-oxo-propylcarbamoyl)-ethyl]-N*4*-hydroxy-succinamide	KI	0.02 nM
(R)-N*1*-[(S)-2-Cyclohexyl-1-(4-dimethylamino-butylcarbamoyl)-ethyl]-N*4*-hydroxy-2-(3-p-tolyl-propyl)-succinamide	KI	0.02 nM
alpha-tetrahydropyran beta-sulfone 1B	IC50	0.029 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-((S)-2-cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-succinamide	KI	0.03 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{2-cyclohexyl-1-[2-(4-morpholin-4-yl-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.03 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-(2-cyclohexyl-1-{2-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethylcarbamoyl}-ethyl)-N*4*-hydroxy-succinamide	KI	0.03 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{(S)-2-cyclohexyl-1-[2-(4-sulfamoyl-phenyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.03 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-[(S)-2-cyclohexyl-1-(4-morpholin-4-yl-butylcarbamoyl)-ethyl]-N*4*-hydroxy-succinamide	KI	0.03 nM
CHEMBL5412341	IC50	0.034 nM
(2R)-3-methyl-2-[(4-phenylbenzene)sulfonamido]butanoic acid	IC50	0.04 nM
N-Hydroxy-2-(4-phenoxy-benzenesulfonylamino)-acetamide	IC50	0.04 nM
CHEMBL4746390	KI	0.044 nM
CHEMBL5209489	IC50	0.044 nM
CHEMBL5288452	IC50	0.0449 nM
CHEMBL5203315	IC50	0.046 nM
AG-3340	IC50	0.048 nM
(S)-2,2-Dimethyl-4-[4-(pyridin-3-yloxy)-benzenesulfonyl]-thiomorpholine-3-carboxylic acid hydroxyamide	IC50	0.048 nM
CHEMBL4522121	IC50	0.048 nM
2-[3-(4-Chloro-phenyl)-propyl]-N*1*-{2-cyclohexyl-1-[2-(4-dimethylamino-butylcarbamoyl)-ethylcarbamoyl]-ethyl}-N*4*-hydroxy-succinamide	KI	0.05 nM
(R)-2-[3-(4-Chloro-phenyl)-propyl]-N*1*-[(S)-2-cyclohexyl-1-(4-dimethylamino-butylcarbamoyl)-ethyl]-N*4*-hydroxy-succinamide	KI	0.05 nM
CHEMBL473539	IC50	0.05 nM
CHEMBL5207094	IC50	0.051 nM
CHEMBL5183245	IC50	0.055 nM
CHEMBL5182207	IC50	0.055 nM
(R)-N*1*-((S)-2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-2-(3-phenyl-propyl)-succinamide	KI	0.06 nM
(R)-N*1*-((S)-2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-2-[3-(4-fluoro-phenyl)-propyl]-N*4*-hydroxy-succinamide	KI	0.06 nM
N*1*-(2-Cyclohexyl-1-phenethylcarbamoyl-ethyl)-N*4*-hydroxy-2-[3-(4-methoxy-phenyl)-propyl]-succinamide	KI	0.06 nM
2-(4’-Chloro-biphenyl-4-ylsulfanylmethyl)-N-hydroxy-4-(4-oxo-4H-benzo[d][1,2,3]triazin-3-yl)-butyramide	IC50	0.06 nM
CHEMBL5280430	IC50	0.065 nM
CHEMBL5191373	IC50	0.066 nM
CHEMBL5185612	IC50	0.068 nM
CHEMBL2064548	IC50	0.07 nM
6-Hydroxy-2-(4-nitro-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline-1-carboxylic acid hydroxyamide	IC50	0.076 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

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

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

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01418118	Phase 4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT03017053	Phase 4	UNKNOWN	The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor
NCT03684707	Phase 4	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions
NCT02270736	Phase 3	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	Phase 3	COMPLETED	Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC
NCT00158678	Phase 3	COMPLETED	IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC
NCT00402779	Phase 3	COMPLETED	Erlotinib Prevention of Oral Cancer (EPOC)
NCT00655421	Phase 3	UNKNOWN	Oral Cancer Screening in Mumbai, India by Primary Health Care Workers
NCT00750503	Phase 3	COMPLETED	Workplace Tobacco Cessation And Oral Cancer Screening Study
NCT00964977	Phase 3	COMPLETED	Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis.
NCT01039298	Phase 3	UNKNOWN	Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL
NCT03685409	Phase 3	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions
NCT05721755	Phase 3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT06589804	Phase 3	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	Phase 3	RECRUITING	Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:
NCT07402538	Phase 3	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	Phase 3	RECRUITING	Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
NCT07827872	Phase 3	NOT_YET_RECRUITING	Neoadjuvant Sintilimab Plus Chemotherapy for cT2N0M0 Oral Squamous Cell Carcinoma
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00330382	Phase 2	COMPLETED	Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
NCT00400205	Phase 2	TERMINATED	Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil
NCT00933387	Phase 2	COMPLETED	A Study of Neoadjuvant Bio-C/T Followed by Concurrent Bio-R/T in High-risk Locally Advanced Oral Squamous Cell Carcinoma
NCT01440270	Phase 2	COMPLETED	Neo-adjuvant Erbitux-based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer
NCT01733797	Phase 2	COMPLETED	Trismus Trial of Therabite vs Wooden Spatula in Head and Neck Cancer Patients
NCT02734537	Phase 2	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	Phase 2	UNKNOWN	uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer
NCT03008694	Phase 2	UNKNOWN	Effect of FDG-PET/CT for Simulation and Radiation Treatment Planning in Oral Cancer Patients
NCT03174275	Phase 2	ACTIVE_NOT_RECRUITING	Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma
NCT03383094	Phase 2	ACTIVE_NOT_RECRUITING	Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
NCT03529422	Phase 2	ACTIVE_NOT_RECRUITING	Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN
NCT04191460	Phase 2	COMPLETED	Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer
NCT04251949	Phase 2	COMPLETED	Evaluation of the Photobiomodulation Using LED Lamp for Curative Treatment of Radio-induced Mucositis.
NCT04541355	Phase 2	COMPLETED	Sodium Thiosulfate in Preventing Ototoxicity for Squamous Cell Cancer Patients Undergoing Chemoradiation With Cisplatin
NCT04862650	Phase 2	ACTIVE_NOT_RECRUITING	Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT05136196	Phase 2	RECRUITING	BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
NCT05172258	Phase 2	ACTIVE_NOT_RECRUITING	Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
NCT05456022	Phase 2	UNKNOWN	Therapeutic Efficacy of Quercetin Versus Its Encapsulated Nanoparticle on Tongue Squamous Cell Carcinoma Cell Line
NCT05941338	Phase 2	RECRUITING	Tirelizumab in Combination With Carboplatin and Albumin-binding Paclitaxel for Neoadjuvant Therapy in HNSCC
NCT05980702	Phase 2	RECRUITING	4 Courses vs 2 Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel of Neoadjuvant Therapy in HNSCC
NCT06084845	Phase 2	WITHDRAWN	Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer
NCT06130332	Phase 2	RECRUITING	Neoadjuvant Tirellizumab Combined With Chemotherapy for Early Oral Squamous Cell Carcinoma(HNC-SYSU-004)
NCT06532279	Phase 2	RECRUITING	Testing the Addition of the Drug BMX-001, a Radioprotector, or a Placebo to the Usual Chemoradiation Therapy for Patients With Head and Neck Cancer
NCT06627270	Phase 2	RECRUITING	Antibiotic Treatment Effects on Intratumoral Bacteria Modulation in Surgical Patients With Oral Cancer
NCT06636734	Phase 2	RECRUITING	Lovastatin and Pembrolizumab for the Treatment of Patients With Recurrent or Metastatic Head and Neck Cancer, LAPP Trial
NCT06876038	Phase 2	NOT_YET_RECRUITING	Low-cost Screening and Image-guided Photodynamic Therapy (PDT) of Premalignant and Malignant Oral Lesions
NCT06980038	Phase 2	RECRUITING	Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer
NCT06997068	Phase 2	RECRUITING	Methotrexate, Erlotinib, and Celecoxib for the Treatment of Recurrent/Metastatic Head and Neck Cancer in a Rural Midwest United States Population
NCT07121595	Phase 2	RECRUITING	Personalized Neck Radiation Therapy Directed by Sentinel Lymph Node Biopsy for the Treatment of Oral Cavity Squamous Cell Carcinoma, PRECEDENT Trial
NCT07195734	Phase 2	RECRUITING	Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MMP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.