MMP14

Summary

MMP14 (matrix metallopeptidase 14, HGNC:7160) is a protein-coding gene on chromosome 14q11.2, encoding Matrix metalloproteinase-14 (P50281). Endopeptidase that degrades various components of the extracellular matrix such as collagen.

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion.

Source: NCBI Gene 4323 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Winchester syndrome (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 382 total — 2 pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004995

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7160
Approved symbol	MMP14
Name	matrix metallopeptidase 14
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MT1-MMP
Ensembl gene	ENSG00000157227
Ensembl biotype	protein_coding
OMIM	600754
Entrez	4323

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 non_stop_decay, 1 protein_coding_CDS_not_defined

ENST00000311852, ENST00000547074, ENST00000547279, ENST00000547596, ENST00000548162, ENST00000548761, ENST00000680097, ENST00000680941, ENST00000928197, ENST00000928199

RefSeq mRNA: 1 — MANE Select: NM_004995 NM_004995

CCDS: CCDS9577

Canonical transcript exons

ENST00000311852 — 10 exons

Exon	Start	End
ENSE00001431522	22845708	22847758
ENSE00002374150	22836585	22836925
ENSE00003493963	22841491	22841639
ENSE00003495503	22843710	22843870
ENSE00003499980	22844371	22844509
ENSE00003503061	22844630	22844780
ENSE00003548702	22845251	22845366
ENSE00003555079	22842410	22842717
ENSE00003635990	22841913	22842035
ENSE00003660436	22843257	22843418

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 195.0155 / max 7643.4905, expressed in 1488 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138824	158.6884	1478
138823	19.8304	1397
138825	7.5058	1136
138826	6.9820	1208
138827	1.8970	662
138829	0.1120	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.72	gold quality
mucosa of stomach	UBERON:0001199	99.16	gold quality
gall bladder	UBERON:0002110	98.68	gold quality
endocervix	UBERON:0000458	98.62	gold quality
body of uterus	UBERON:0009853	98.30	gold quality
ectocervix	UBERON:0012249	98.22	gold quality
smooth muscle tissue	UBERON:0001135	97.70	gold quality
right coronary artery	UBERON:0001625	97.67	gold quality
popliteal artery	UBERON:0002250	97.62	gold quality
tibial artery	UBERON:0007610	97.62	gold quality
skin of leg	UBERON:0001511	97.59	gold quality
thoracic aorta	UBERON:0001515	97.48	gold quality
aorta	UBERON:0000947	97.46	gold quality
ascending aorta	UBERON:0001496	97.46	gold quality
descending thoracic aorta	UBERON:0002345	97.42	gold quality
right ovary	UBERON:0002118	97.34	gold quality
left coronary artery	UBERON:0001626	97.20	gold quality
skin of abdomen	UBERON:0001416	97.16	gold quality
left uterine tube	UBERON:0001303	97.15	gold quality
left ovary	UBERON:0002119	97.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.94	gold quality
minor salivary gland	UBERON:0001830	96.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.57	gold quality
lower esophagus	UBERON:0013473	96.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.54	gold quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
omental fat pad	UBERON:0010414	96.39	gold quality
coronary artery	UBERON:0001621	96.35	gold quality
peritoneum	UBERON:0002358	96.35	gold quality
right lung	UBERON:0002167	96.34	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	100.01
E-MTAB-8142	yes	100.01
E-MTAB-8410	yes	43.26
E-CURD-112	yes	14.95
E-ANND-3	yes	12.64
E-GEOD-83139	yes	7.70
E-ENAD-27	yes	7.28
E-MTAB-7249	yes	3.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, CTNNBIP1, E2F1, EGR1, EPAS1, ETV4, FHIT, GLI1, HIF1A, HNF4A, HOXA3, KAT5, KLF8, MAZ, NFATC1, NFKB1, NFKB, RELA, RUNX2, SP1, SP3, SRF, STAT3, ZBTB7A

miRNA regulators (miRDB)

80 targeting MMP14, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325

Literature-anchored findings (GeneRIF, showing 40)

• MT1-MMP plays an important role during endothelial cell migration, and its activity can modulate endothelial migration, invasion, and formation of capillary tubes during the angiogenic response. (PMID:11448964)
• Thus, MT1-MMP oligomerization through the hemopexin, transmembrane, and cytoplasmic domains controls its catalytic activity. (PMID:11779859)
• Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis. (PMID:11809713)
• 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)
• Refolding of the catalytic and hinge domains of human MT1-mMP expressed in Escherichia coli and its characterization. (PMID:11911461)
• increasing expression and endometrial carcinoma appear closely related (PMID:11920503)
• Levels of MMP14 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)
• studies suggest that ectodomain shedding regulates the pericellular and extracellular activities of MT1-MMP through a delicate balance of active and inactive enzyme-soluble fragments (PMID:12004057)
• Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism. (PMID:12115722)
• CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain. (PMID:12145196)
• MT1-MMP is primarily secreted in the oral squamous cell carcinoma (OSCC) cells and is involved in the invasiveness of the OSCC and lymphatic metastasis. (PMID:12169394)
• Expression of MT1-MMP was elevated in 22 of 24 colon carcinomas we examined.DNA fragment between -1169 bp and -1163 bp in the 5’ flanking region of this gene to be a target of the beta-catenin/Tcf4 complex. (PMID:12185585)
• required for calcium regulation of matrix metalloproteinase-2 activation in oral squamous cell carcinoma cells (PMID:12194986)
• demonstrate that MT1-MMP via its cytoplasmic tail directly associates with a chaperone-like compartment-specific regulator gC1qR (PMID:12220632)
• 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)
• MT1-MMP 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)
• Data show a novel mechanism by which ECM regulates membrane-type 1 matrix metalloproteinase (MT1-MMP) association with beta1 or alphavbeta3 integrins, thus modulating its internalization, activity, and function on human endothelial cells. (PMID:12427871)
• laminin-5 as a substrate for mTLD, suggesting a role for laminin-5 processing by mTLD in the skin. (PMID:12473650)
• Results demonstrate the ability of hepatitis B virus X protein to promote tumor cell invasion by a mechanism involving the upregulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) and cyclooxygenase-2 (COX-2). (PMID:12488433)
• matrix metalloproteinase-2 and 9 and membrane-type 1 matrix metalloproteinase mRNA expression in endometriosis was higher than in normal endometrium whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriosis (PMID:12587534)
• down-regulation of most MT-MMPs is typical for prostate carcinoma; seems to occur mainly in epithelial cells (PMID:12661033)
• results implicate myofibroblasts as major producer of MT1-MMP in breast cancer and emphasize the importance of stromal-epithelial cell interactions in their progression (PMID:12672023)
• Data demonstrate that blockade of the ERK pathway suppressed the expression of matrix metalloproteinases 3, 9, and 14, and CD44, and markedly inhibited the invasiveness of tumor cells. (PMID:12727228)
• identify the surface epitopes that render TIMP-1 inactive against MT1-MMP (PMID:12869573)
• shedding of syndecan-1 promoted by MT1-MMP through the preferential cleavage of Gly245-Leu246 peptide bond stimulates cell migration (PMID:12904296)
• MT1-MMP-controlled cross-talk between alphavbeta3 and alpha2beta1 integrins supports binding of aggressive, MT1-MMP-, and alphavbeta3 integrin-expressing malignant cells on type I collagen, the most common substratum of the extracellular matrix (PMID:14597417)
• the presentation of LDL receptor-related protein LRP and the subsequent uptake of its ligands by malignant cells are both strongly regulated by MT1-MMP (PMID:14645246)
• data provide evidence for an additional mechanism for post-translational control of membrane type 1 matrix metalloproteinase (MT1-MMP) activity and suggest that glycosylation of MT1-MMP may regulate its substrate targeting (PMID:14670950)
• Expression of MT1-MMP is transcriptionally induced by FGF1 in a prostate carcinoma cell line/ (PMID:14673954)
• Low levels of MT1-MMP, MMP-1 and AI were found to be favourable markers significantly associated with longer survival in advanced colorectal carcinoma (PMID:14707454)
• during angiogenesis the full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways. (PMID:14729679)
• MT1-MMP activity is regulated by ERK 1/2- and p38 MAPK-modulated TIMP-2 expression which controls TGF-beta1-induced pericellular collagenolysis (PMID:15247230)
• Data suggest that in furin-negative colon carcinoma cells membrane type-1 matrix metalloproteinase is autocatalytically processed and the active protease then operates as a prointegrin convertase. (PMID:15260832)
• The activity of membrane-type 1 matrix metalloproteinase (MT1-MMP) is a double-edged sword-it is crucial for both physiological processes and disease progression. (PMID:15276180)
• Collagenolytic MMP-14 is found to be more efficient at processing triple-helical peptidase substrates than is MMP-1. (PMID:15350133)
• MT1-MMP intracellular transport toward the plasma membrane is regulated by syntaxin 4 (PMID:15351710)
• MT1-MMP cleaves complement C3b (PMID:15381670)
• the hemopexin domain of MT1-MMP is not required for the activation of proMMP2 on cell surface but is essential for MT1-MMP-mediated invasion in three-dimensional type I collagen (PMID:15381707)
• identified substrates of MMP-14 in plasma (PMID:15450852)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp14a	ENSDARG00000002235
danio_rerio	mmp14b	ENSDARG00000008388
mus_musculus	Mmp14	ENSMUSG00000000957
rattus_norvegicus	Mmp14	ENSRNOG00000010947
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-14 — P50281 (reviewed: P50281)

Alternative names: MMP-X1, Membrane-type matrix metalloproteinase 1, Membrane-type-1 matrix metalloproteinase

All UniProt accessions (5): P50281, A0A7P0TAG0, A0A7P0TAV6, A0A7P0TBK8, F8VP90

UniProt curated annotations — full annotation on UniProt →

Function. Endopeptidase that degrades various components of the extracellular matrix such as collagen. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development. Activates progelatinase A/MMP2, thereby acting as a positive regulator of cell growth and migration. Involved in the formation of the fibrovascular tissues in association with pro-MMP2. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a regulator of Notch signaling by mediating cleavage and inhibition of DLL1. Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis. Acts as a negative regulator of the GDF15-GFRAL aversive response by mediating cleavage and inactivation of GFRAL.

Subunit / interactions. Interacts (via C-terminal cytoplasmic tail) with BST2.

Subcellular location. Cell membrane. Melanosome. Cytoplasm.

Tissue specificity. Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase. Tyrosine phosphorylated by PKDCC/VLK.

Disease relevance. Winchester syndrome (WNCHRS) [MIM:277950] A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion 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. Up-regulated by NANOS1.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_004986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR002477	Peptidoglycan-bd-like	Domain
IPR006026	Peptidase_Metallo	Domain
IPR018486	Hemopexin_CS	Conserved_site
IPR018487	Hemopexin-like_repeat	Repeat
IPR021158	Pept_M10A_Zn_BS	Binding_site
IPR021190	Pept_M10A	Family
IPR021805	Pept_M10A_metallopeptidase_C	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036366	PGBDSf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471, PF11857

Enzyme classification (BRENDA):

• EC 3.4.24.80 — membrane-type matrix metalloproteinase-1 (BRENDA: 10 organisms, 200 substrates, 146 inhibitors, 32 Km, 29 kcat entries)
• EC 3.4.24.B5 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
(GLY-PRO-HYP)5-GLY-PRO-LYS(MCA)-GLY-PRO-GLN-GLY-	0.0151–0.0368	4
COLLAGEN I ALPHA-1 CHAIN	0.0003–0.32	4
COLLAGEN I ALPHA-2 CHAIN	0.0006–0.12	4
COLLAGEN TYPE I ALPHA-1 CHAIN	0.0009–0.17	4
COLLAGEN TYPE I ALPHA-2 CHAIN	0.0003–0.53	4
METHOXYCOUMARIN-4-ACETYL-LYS-PRO-LEU-GLY-LEU-LYS	0.0006–0.0028	4
MOCACPLGLA2PR-DINITROPHENOL-A-RNH2	0.009–0.01	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-PRO-LEU-GLY-LEU-N	0.0034	1
TYPE I COLLAGEN CHAIN ALPHA-1	—	1
TYPE I COLLAGEN CHAIN ALPHA-2	—	1

UniProt features (89 total): strand 31, binding site 17, sequence variant 9, helix 9, turn 5, repeat 4, topological domain 2, sequence conflict 2, signal peptide 1, propeptide 1, region of interest 1, short sequence motif 1, active site 1, chain 1, modified residue 1, disulfide bond 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
3C7X	X-RAY DIFFRACTION	1.7
4P3C	X-RAY DIFFRACTION	1.94
4P3D	X-RAY DIFFRACTION	1.95
3MA2	X-RAY DIFFRACTION	2.05
5H0U	X-RAY DIFFRACTION	2.24
4QXU	X-RAY DIFFRACTION	2.3
3X23	X-RAY DIFFRACTION	2.4
1BQQ	X-RAY DIFFRACTION	2.75
1BUV	X-RAY DIFFRACTION	2.75
2MQS	SOLUTION NMR
6CLZ	SOLUTION NMR
6CM1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50281-F1	81.66	0.58

Antibody-complex structures (SAbDab): 3 — 4P3C, 4P3D, 4QXU

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): 240

Ligand- & substrate-binding residues (17): 93 (in inhibited form); 186; 188; 193; 194; 196; 198; 201; 208; 210; 212; 214 …

Post-translational modifications (1): 399

Disulfide bonds (1): 319–508

Mutagenesis-validated functional residues (1):

Position	Phenotype
240	in mt1 ea mutant; abolished endopeptidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-9839383	TGFBR3 PTM regulation
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3
R-HSA-9855142	Cellular responses to mechanical stimuli
R-HSA-9860931	Response of endothelial cells to shear stress

MSigDB gene sets: 565 (showing top): MODULE_172, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_POSITIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, GOBP_B_CELL_ACTIVATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, TGCACTT_MIR519C_MIR519B_MIR519A

GO Biological Process (45): skeletal system development (GO:0001501), angiogenesis (GO:0001525), ovarian follicle development (GO:0001541), response to hypoxia (GO:0001666), endothelial cell proliferation (GO:0001935), endochondral ossification (GO:0001958), proteolysis (GO:0006508), response to oxidative stress (GO:0006979), male gonad development (GO:0008584), response to mechanical stimulus (GO:0009612), positive regulation of myotube differentiation (GO:0010831), positive regulation of protein processing (GO:0010954), protein processing (GO:0016485), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), extracellular matrix organization (GO:0030198), positive regulation of cell growth (GO:0030307), lung development (GO:0030324), positive regulation of cell migration (GO:0030335), collagen catabolic process (GO:0030574), zymogen activation (GO:0031638), endodermal cell differentiation (GO:0035987), chondrocyte proliferation (GO:0035988), astrocyte cell migration (GO:0043615), response to estrogen (GO:0043627), positive regulation of B cell differentiation (GO:0045579), negative regulation of Notch signaling pathway (GO:0045746), embryonic cranial skeleton morphogenesis (GO:0048701), branching morphogenesis of an epithelial tube (GO:0048754), tissue remodeling (GO:0048771), cell motility (GO:0048870), negative regulation of focal adhesion assembly (GO:0051895), head development (GO:0060322), cellular response to genistein (GO:0071412), craniofacial suture morphogenesis (GO:0097094), negative regulation of GDF15-GFRAL signaling pathway (GO:0160145), regulation of protein localization to plasma membrane (GO:1903076), positive regulation of macrophage migration (GO:1905523), response to odorant (GO:1990834), ossification (GO:0001503)

GO Molecular Function (11): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), integrin binding (GO:0005178), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (13): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), Golgi lumen (GO:0005796), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), extracellular matrix (GO:0031012), cytoplasmic vesicle (GO:0031410), melanosome (GO:0042470), macropinosome (GO:0044354), intermediate filament cytoskeleton (GO:0045111), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	1
Signaling by TGFBR3	1
Response of endothelial cells to shear stress	1
Signal Transduction	1
Signaling by TGFB family members	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to stress	2
protein metabolic process	2
peptidase activity	2
endopeptidase activity	2
cytoplasm	2
system development	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
female gonad development	1
anatomical structure development	1
response to decreased oxygen levels	1
epithelial cell proliferation	1
replacement ossification	1
endochondral bone morphogenesis	1
gonad development	1
development of primary male sexual characteristics	1
response to external stimulus	1
response to abiotic stimulus	1
regulation of myotube differentiation	1
myotube differentiation	1
positive regulation of striated muscle cell differentiation	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
proteolysis	1
protein maturation	1
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
respiratory tube development	1
animal organ development	1
respiratory system development	1

Protein interactions and networks

STRING

2592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP14	TIMP2	P16035	999
MMP14	TIMP1	P01033	996
MMP14	MMP2	P08253	961
MMP14	ADI1	Q9BV57	930
MMP14	CD44	P16070	912
MMP14	RECK	O95980	892
MMP14	TIMP3	P35625	872
MMP14	TIMP4	Q99727	869
MMP14	MMP9	P14780	822
MMP14	SH3PXD2B	A1X283	816
MMP14	HCLS1	P14317	789
MMP14	CTTN	Q14247	788
MMP14	FN1	P02751	787
MMP14	SH3PXD2A	Q5TCZ1	743
MMP14	SRC	P12931	724

IntAct

134 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
MMP14	Gorasp2	psi-mi:“MI:0915”(physical association)	0.600
Gorasp2	MMP14	psi-mi:“MI:0915”(physical association)	0.600
Gorasp2	MMP14	psi-mi:“MI:0403”(colocalization)	0.600
MMP14	ADI1	psi-mi:“MI:0915”(physical association)	0.600
ADI1	MMP14	psi-mi:“MI:0915”(physical association)	0.600
ADI1	MMP14	psi-mi:“MI:0403”(colocalization)	0.600
KASH5	MMP14	psi-mi:“MI:0915”(physical association)	0.560
MMP14	FURIN	psi-mi:“MI:0915”(physical association)	0.560
MMP14	ZUP1	psi-mi:“MI:0915”(physical association)	0.560
MMP14	FHL3	psi-mi:“MI:0915”(physical association)	0.560
	MMP14	psi-mi:“MI:0915”(physical association)	0.560
MMP14	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
MMP14	AQP6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (96): CCDC155 (Two-hybrid), SPOCK3 (Affinity Capture-Western), MMP14 (Biochemical Activity), MMP14 (Reconstituted Complex), TIMP2 (Reconstituted Complex), MMP3 (Reconstituted Complex), MMP3 (Biochemical Activity), TIMP1 (Reconstituted Complex), LUM (Biochemical Activity), MMP14 (Co-localization), MMP14 (Affinity Capture-Western), MMP14 (Affinity Capture-Western), MMP14 (Co-fractionation), NPR1 (Negative Genetic), SLC16A8 (Positive Genetic)

ESM2 similar proteins: A0A0C5PRQ1, A6H737, A8Q2D1, D5FM34, D5FM37, E1C3U7, K7Z9Q9, O17264, O35548, O43897, O54732, O57460, O77636, P25723, P50281, P51511, P51512, P55114, P98060, P98069, P98070, Q10739, Q11005, Q18206, Q19204, Q20459, Q20942, Q20958, Q22396, Q22710, Q5RES1, Q5W7F4, Q61EX6, Q62381, Q7Z0M7, Q8JI28, Q8MPP3, Q93243, Q93542, Q94316

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

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
SRC	unknown	MMP14	phosphorylation
FHIT	“down-regulates quantity by repression”	MMP14	“transcriptional regulation”
MMP14	“down-regulates quantity by destabilization”	ADAM9	cleavage
MAP3K14	“up-regulates activity”	MMP14	phosphorylation
TIMP3	“down-regulates activity”	MMP14	binding
MMP14	up-regulates	Adipogenesis
MMP14	“down-regulates quantity by destabilization”	F12	cleavage
MMP14	“down-regulates quantity by destabilization”	FGG	cleavage
MMP14	“down-regulates quantity by destabilization”	FGA	cleavage
MMP14	up-regulates	ECM_disassembly
MMP14	down-regulates	ECM

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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.

GO biological processes:

GO term	Partners	Fold	FDR
response to ethanol	6	14.7×	1e-03
transforming growth factor beta receptor signaling pathway	5	13.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	210
Likely benign	117
Benign	40

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3064215	NM_004995.4(MMP14):c.332G>A (p.Arg111His)	Pathogenic
65463	NM_004995.4(MMP14):c.50C>G (p.Thr17Arg)	Pathogenic

SpliceAI

1728 predictions. Top by Δscore:

Variant	Effect	Δscore
14:22836926:G:GG	donor_gain	1.0000
14:22841489:AGG:A	acceptor_loss	1.0000
14:22841490:GGC:G	acceptor_gain	1.0000
14:22841490:GGCCT:G	acceptor_gain	1.0000
14:22841636:TGAA:T	donor_gain	1.0000
14:22841636:TGAAG:T	donor_loss	1.0000
14:22841637:GAA:G	donor_gain	1.0000
14:22841637:GAAG:G	donor_gain	1.0000
14:22841638:AA:A	donor_gain	1.0000
14:22841638:AAG:A	donor_loss	1.0000
14:22841639:AG:A	donor_loss	1.0000
14:22841640:G:C	donor_loss	1.0000
14:22841640:G:GG	donor_gain	1.0000
14:22841641:T:G	donor_loss	1.0000
14:22842393:A:AG	acceptor_gain	1.0000
14:22842393:AC:A	acceptor_gain	1.0000
14:22842393:ACGT:A	acceptor_gain	1.0000
14:22842393:ACGTG:A	acceptor_gain	1.0000
14:22842394:C:CA	acceptor_gain	1.0000
14:22842396:T:TA	acceptor_gain	1.0000
14:22842397:G:A	acceptor_gain	1.0000
14:22842400:T:A	acceptor_gain	1.0000
14:22842701:GAA:G	donor_gain	1.0000
14:22842716:TGG:T	donor_loss	1.0000
14:22842717:GGTG:G	donor_loss	1.0000
14:22842718:G:A	donor_loss	1.0000
14:22842719:T:G	donor_loss	1.0000
14:22843251:TTCCA:T	acceptor_loss	1.0000
14:22843252:TCCA:T	acceptor_loss	1.0000
14:22843254:CAG:C	acceptor_loss	1.0000

AlphaMissense

3825 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:22841589:G:C	Q69H	1.000
14:22841589:G:T	Q69H	1.000
14:22841932:T:A	C93S	1.000
14:22841932:T:C	C93R	1.000
14:22841933:G:A	C93Y	1.000
14:22841933:G:C	C93S	1.000
14:22841933:G:T	C93F	1.000
14:22841934:T:G	C93W	1.000
14:22842010:T:A	W119R	1.000
14:22842010:T:C	W119R	1.000
14:22842012:G:C	W119C	1.000
14:22842012:G:T	W119C	1.000
14:22842480:T:A	W151R	1.000
14:22842480:T:C	W151R	1.000
14:22842482:G:C	W151C	1.000
14:22842482:G:T	W151C	1.000
14:22842585:C:G	H186D	1.000
14:22842603:T:A	F192I	1.000
14:22842603:T:C	F192L	1.000
14:22842604:T:G	F192C	1.000
14:22842605:C:A	F192L	1.000
14:22842605:C:G	F192L	1.000
14:22842628:C:A	A200D	1.000
14:22842630:C:A	H201N	1.000
14:22842630:C:G	H201D	1.000
14:22842631:A:C	H201P	1.000
14:22842631:A:G	H201R	1.000
14:22842632:T:A	H201Q	1.000
14:22842632:T:G	H201Q	1.000
14:22842634:C:A	A202D	1.000

dbSNP variants (sampled 300 via entrez): RS1000465730 (14:22843993 C>G,T), RS1000492144 (14:22841856 A>G), RS1000553192 (14:22836248 A>C,G), RS1000697215 (14:22847208 G>A), RS1000896018 (14:22839487 G>A), RS1000926575 (14:22839730 T>C), RS1001229106 (14:22840653 C>T), RS1001257967 (14:22840600 C>T), RS1001258778 (14:22840850 T>C), RS1001317790 (14:22846471 A>C), RS1001458828 (14:22835029 T>C), RS1001510637 (14:22836569 A>G), RS1001602009 (14:22846207 C>G,T), RS1001614349 (14:22835450 ATTC>A), RS1001707134 (14:22840762 G>A)

Disease associations

OMIM: gene MIM:600754 | disease phenotypes: MIM:277950

GenCC curated gene-disease

Disease	Classification	Inheritance
Winchester syndrome	Moderate	Autosomal recessive
multicentric osteolysis-nodulosis-arthropathy spectrum	Supportive	Autosomal recessive

Mondo (2): Winchester syndrome (MONDO:0010201), multicentric osteolysis-nodulosis-arthropathy spectrum (MONDO:0018298)

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

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0000212	Gingival overgrowth
HP:0000248	Brachycephaly
HP:0000280	Coarse facial features
HP:0000315	Abnormality of the orbital region
HP:0000612	Iris coloboma
HP:0000822	Hypertension
HP:0000916	Broad clavicles
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001007	Hirsutism
HP:0001059	Pterygium
HP:0001085	Papilledema
HP:0001230	Broad metacarpals
HP:0001249	Intellectual disability
HP:0001369	Arthritis
HP:0001482	Subcutaneous nodule
HP:0001495	Carpal 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:0001999	Abnormal facial shape
HP:0002659	Increased susceptibility to fractures

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004858_17	Dupuytren’s disease	2.000000e-19
GCST006085_59	Prostate cancer	2.000000e-08
GCST006288_161	Heel bone mineral density	4.000000e-07
GCST006288_326	Heel bone mineral density	6.000000e-07
GCST006288_431	Heel bone mineral density	9.000000e-14
GCST006630_42	Diastolic blood pressure	6.000000e-13
GCST006979_1040	Heel bone mineral density	1.000000e-34
GCST007492_1	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-08
GCST007494_3	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1.000000e-07
GCST010483_2	Cardiovascular death, myocardial infarction or stroke in response to clopidogrel treatment	5.000000e-06
GCST90000025_527	Appendicular lean mass	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0006919	cardiovascular event measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536709	Winchester syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3869 (SINGLE PROTEIN), CHEMBL4523971 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 125,854 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200596	CHLOROXINE	4	1,792
CHEMBL1350	TILUDRONIC ACID	4	14,784
CHEMBL4303669	ZOLEDRONIC ACID	4	523
CHEMBL497	CLIOQUINOL	4	12,977
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL75094	PRINOMASTAT	3	8,839
CHEMBL115653	CIPEMASTAT	2	359
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL279786	BATIMASTAT	2	21,247
CHEMBL440498	CTS-1027	2	615
CHEMBL4650334	ALDUMASTAT	2	58
CHEMBL76222	REBIMASTAT	2	344

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
ilomastat	Inhibition	8.96	pIC50
compound 29e [PMID: 23631440]	Inhibition	8.4	pKi
CGS-27023A	Inhibition	7.64	pIC50
(R)-ND-336	Inhibition	6.92	pKi
TP0556351	Inhibition	5.65	pIC50

Binding affinities (BindingDB)

142 measured of 256 human assays (256 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3S)-4-{[4-(but-2-yn-1-yloxy)benzene]sulfonyl}-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide	IC50	4.7 nM
(4S)-5-[3-(carboxymethyl)piperidin-1-yl]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	12 nM	US-8691753
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	18.1 nM	US-8691753
(2R)-3-methyl-2-[(4-{4-[(3-methyl-1-benzofuran-2-yl)methoxy]phenyl}benzene)sulfonamido]butanoic acid	IC50	28 nM
(4S)-5-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	31 nM	US-8691753
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	39 nM	US-8691753
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]pentanoic acid	KI	39.3 nM	US-8691753
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	45 nM	US-8691753
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-N-hydroxy-1-[(2-methylphenyl)carbonyl]piperidine-4-carboxamide	IC50	46 nM
Inhibitor, 18	KI	47 nM
(4S)-5-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	49 nM	US-8691753
(3S)-4-amino-3-[[(2S)-3-carboxy-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-4-oxobutanoic acid	KI	52 nM	US-8691753
5-[3-[(3S)-4-(4-chloro-3,5-difluorophenyl)-3-methylpiperazin-1-yl]-2-methyl-3-oxopropyl]-5-(methoxymethyl)imidazolidine-2,4-dione	IC50	53 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
(4S)-5-[[(2S)-1-amino-3-carboxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	55 nM	US-8691753
Inhibitor, 17	KI	57 nM
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	65 nM	US-8691753
MMP Inhibitor, 2	IC50	66 nM
(4S)-5-[[1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	68 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	73 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	76 nM	US-8691753
(4S)-5-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]pentanoic acid	KI	78 nM	US-8691753
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]pentanoic acid	KI	83 nM	US-8691753
(3S)-4-amino-3-[[(2S)-3-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-4-oxobutanoic acid	KI	86 nM	US-8691753
(4S)-5-amino-4-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]-5-oxopentanoic acid	KI	90 nM	US-8691753
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	91 nM	US-8691753
(3S)-4-amino-4-oxo-3-[[(2S)-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]butanoic acid	KI	93 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[4-(5-methylthiophen-2-yl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	97 nM	US-8691753
(4S)-5-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	110 nM	US-8691753
(4R)-5-amino-4-[[(2S)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	112 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-carboxy-1-oxopropan-2-yl]amino]-4-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]-5-oxopentanoic acid	KI	112 nM	US-8691753
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	116 nM	US-8691753
tert-butyl 4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-4-(hydroxycarbamoyl)piperidine-1-carboxylate	IC50	120 nM
(5S)-5-cyclopropyl-5-[3-[(3S)-4-(3,5-difluorophenyl)-3-methylpiperazin-1-yl]-3-oxopropyl]imidazolidine-2,4-dione	IC50	123 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-[3-[(3S)-4-(3-fluorophenyl)-3-methylpiperazin-1-yl]-3-oxopropyl]-5-pyrazin-2-ylimidazolidine-2,4-dione	IC50	123 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-[3-[(3S)-4-(4-chloro-3,5-difluorophenyl)-3-methylpiperazin-1-yl]-2-methyl-3-oxopropyl]-5-methylimidazolidine-2,4-dione	IC50	123 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
Inhibitor, 16	KI	127 nM
(4S)-5-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	140 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-(4-thiophen-2-ylphenyl)propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	142 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	147 nM	US-8691753
(5S)-6-amino-5-[[(2S)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-6-oxohexanoic acid	KI	150 nM	US-8691753
(4S)-5-amino-4-[[(2S)-2-[3-[4-(1,3-benzothiazol-2-yl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	151 nM	US-8691753
(5S)-5-cyclopropyl-5-[(2S)-3-[(3S)-4-(3,4-difluorophenyl)-3-methylpiperazin-1-yl]-2-methyl-3-oxopropyl]imidazolidine-2,4-dione	IC50	192 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-cyclopropyl-5-[3-[(3S)-3-methyl-4-pyridin-3-ylpiperazin-1-yl]-3-oxopropyl]imidazolidine-2,4-dione	IC50	192 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-[3-[(3S)-4-(3-chloro-5-fluorophenyl)-3-methylpiperazin-1-yl]-3-oxopropyl]-5-(6-methyl-2-pyridinyl)imidazolidine-2,4-dione	IC50	192 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
RXP470, Compound 4	KI	192 nM
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	204 nM	US-8691753
(5S)-5-[(2S)-3-[(3S)-4-(3-chloro-4-fluorophenyl)-3-methylpiperazin-1-yl]-2-methyl-3-oxopropyl]-5-(methoxymethyl)imidazolidine-2,4-dione	IC50	209 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-(2-aminoethyl)-5-[3-[4-(3,5-dichlorophenyl)piperazin-1-yl]-2-methyl-3-oxopropyl]imidazolidine-2,4-dione	IC50	212 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
4-({[4-(but-2-yn-1-ylamino)benzene]sulfonyl}methyl)-1-N,1-N-diethyl-4-N-hydroxypiperidine-1,4-dicarboxamide	IC50	216 nM
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-(4-thiophen-3-ylphenyl)propanoylamino]butanoyl]amino]pentanoic acid	KI	225 nM	US-8691753

ChEMBL bioactivities

768 potent at pChembl≥5 of 966 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	PRINOMASTAT
9.49	IC50	0.32	nM	CHEMBL471537
9.48	IC50	0.33	nM	CHEMBL473539
9.39	IC50	0.41	nM	ILOMASTAT
9.14	IC50	0.73	nM	CHEMBL1801422
9.05	IC50	0.9	nM	CHEMBL1092104
8.96	IC50	1.1	nM	CTS-1027
8.96	IC50	1.1	nM	ILOMASTAT
8.92	IC50	1.2	nM	CHEMBL1766900
8.89	IC50	1.3	nM	CHEMBL1766899
8.88	IC50	1.33	nM	CHEMBL1801397
8.82	IC50	1.5	nM	CHEMBL263750
8.77	IC50	1.71	nM	CHEMBL1801048
8.74	IC50	1.8	nM	MARIMASTAT
8.74	IC50	1.82	nM	MARIMASTAT
8.72	IC50	1.9	nM	RO-319790
8.72	IC50	1.9	nM	CHEMBL20154
8.68	IC50	2.1	nM	CHEMBL234530
8.68	IC50	2.08	nM	CHEMBL279078
8.64	IC50	2.3	nM	CHEMBL281371
8.60	IC50	2.5	nM	CHEMBL20043
8.54	IC50	2.9	nM	BATIMASTAT
8.52	IC50	3	nM	CHEMBL367133
8.52	IC50	3	nM	CHEMBL5205063
8.52	IC50	3	nM	BATIMASTAT
8.51	IC50	3.1	nM	CHEMBL1801057
8.47	IC50	3.4	nM	CHEMBL1078281
8.44	IC50	3.63	nM	CHEMBL1801053
8.43	IC50	3.7	nM	CHEMBL1801393
8.42	IC50	3.8	nM	CHEMBL3932562
8.41	IC50	3.9	nM	CHEMBL3617407
8.41	IC50	3.9	nM	CHEMBL515980
8.40	IC50	4	nM	CHEMBL198778
8.40	Ki	4	nM	CHEMBL2380402
8.40	IC50	4	nM	CHEMBL1801421
8.39	IC50	4.1	nM	CHEMBL1801431
8.37	IC50	4.3	nM	CHEMBL1089843
8.35	IC50	4.5	nM	CHEMBL1801045
8.34	IC50	4.6	nM	BATIMASTAT
8.34	IC50	4.6	nM	CHEMBL1801430
8.33	IC50	4.7	nM	ILOMASTAT
8.30	Ki	5	nM	CHEMBL2380403
8.30	IC50	5	nM	CHEMBL1957606
8.28	IC50	5.2	nM	ILOMASTAT
8.27	IC50	5.4	nM	CHEMBL3889936
8.25	IC50	5.6	nM	CHEMBL1801046
8.22	Ki	6	nM	CHEMBL2380389
8.21	Ki	6.2	nM	CHEMBL2380387
8.18	Ki	6.6	nM	CHEMBL2380403
8.17	IC50	6.8	nM	CHEMBL1801412

PubChem BioAssay actives

695 with measured affinity, of 1442 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R)-N-hydroxy-3-methyl-2-[[2-oxo-2-[2-(4-sulfamoylphenyl)ethylamino]ethyl]-(4-phenoxyphenyl)sulfonylamino]butanamide	413961: Inhibition of MMP14	ic50	0.0003	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-phenoxyphenyl)sulfonylthiomorpholine-3-carboxamide	1863882: Inhibition of MMP-14 (unknown origin)	ic50	0.0003	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	241672: Inhibition of human matrix metalloprotease-14	ic50	0.0003	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	628296: Inhibition of MMP14	ic50	0.0004	uM
4-[4-(1,3-benzodioxol-5-yloxy)phenyl]sulfonyl-1-cyclopropyl-N-hydroxypiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0007	uM
(2R)-2-[(4-bromophenyl)sulfonylamino]-4-(1,3-dioxoisoindol-2-yl)-N-hydroxybutanamide	473232: Inhibition of human recombinant MMP14 by fluorometric assay	ic50	0.0009	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162791: Inhibition of human recombinant MMP14 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0011	uM
(1S,2R,3R)-2-methyl-1-[[5-(4-methylpyrazol-1-yl)thiophen-2-yl]sulfonylamino]-3-phenylcyclopropane-1-carboxylic acid	593446: Inhibition of human recombinant MMP14 after 60 mins by fluorescence plate reader	ic50	0.0012	uM
N-hydroxy-1-prop-2-ynyl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0013	uM
(1S,2R,3R)-1-[[5-(4-methoxypyrazol-1-yl)thiophen-2-yl]sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593446: Inhibition of human recombinant MMP14 after 60 mins by fluorescence plate reader	ic50	0.0013	uM
(2S)-2-[[4-[4-[(5-methoxy-1-benzofuran-2-carbonyl)amino]phenyl]phenyl]sulfonylamino]-3-methylbutanoic acid	240552: Inhibitory concentration against MMP-14	ic50	0.0015	uM
N-hydroxy-4-[4-(4-hydroxyphenoxy)phenyl]sulfonyloxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0017	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	1863882: Inhibition of MMP-14 (unknown origin)	ic50	0.0018	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-(3-phenylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0019	uM
(2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0019	uM
(2S,3R)-N-hydroxy-2-methyl-N’-[(2S)-1-(methylamino)-1-oxo-3-(5,6,7,8-tetrahydronaphthalen-1-yl)propan-2-yl]-3-(2-methylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0021	uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-phenoxyphenyl)sulfonylamino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide	413961: Inhibition of MMP14	ic50	0.0021	uM
(2R)-N-[(1S)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0023	uM
(2R)-N’-hydroxy-N-[(2S)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]-2-(3-phenylpropyl)butanediamide	220527: Activity against deletion mutant of MT1-MMP lacking the transmembrane domain (deltaMT1)	ic50	0.0025	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide	109549: Inhibition of Matrix metalloprotease-14	ic50	0.0029	uM
5-amino-3-(2-ethoxyethyl)-3-[4-[4-(1,3-oxazol-5-yl)phenoxy]phenoxy]piperidine-2,4,6-trione	241034: Inhibitory concentration against matrix metalloprotease 14	ic50	0.0030	uM
(2S,3R,6R)-6-benzyl-N-hydroxy-N’-methyl-3-(2-methylpropyl)-4-oxo-2-(thiophen-2-ylsulfanylmethyl)heptanediamide	1863882: Inhibition of MMP-14 (unknown origin)	ic50	0.0030	uM
N-hydroxy-4-[4-(4-methoxyphenoxy)phenyl]sulfonyl-1-(pyridin-2-ylmethyl)piperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0031	uM
(1S,2R,3R)-1-[[5-(4-chloropyrazol-1-yl)thiophen-2-yl]sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593446: Inhibition of human recombinant MMP14 after 60 mins by fluorescence plate reader	ic50	0.0034	uM
N-hydroxy-4-[4-(4-methylsulfanylphenoxy)phenyl]sulfonyloxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0036	uM
N-hydroxy-1-(pyridin-3-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0037	uM
N-[[3-[4-[[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]phenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328783: Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0038	uM
(2R)-4-(1,3-dioxoisoindol-2-yl)-N-hydroxy-2-[[4-(4-methoxyphenyl)phenyl]sulfonyl-propan-2-yloxyamino]butanamide	1246458: Inhibition of recombinant human catalytic domain MMP14 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as fluorogenic substrate incubated for 4 hrs followed by substrate addition measured every 10 secs for 20 mins by fluorometric assay	ic50	0.0039	uM
2-[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-phenoxyphenyl)sulfonylamino]acetic acid	413961: Inhibition of MMP14	ic50	0.0039	uM
4-[4-(1,3-benzodioxol-5-yloxy)phenyl]sulfonyl-N-hydroxy-1-(2-methoxyethyl)piperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0040	uM
N-hydroxy-2-[(4-phenoxyphenyl)sulfonylamino]acetamide	736083: Inhibition of human recombinant MMP14 catalytic domain 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	0.0040	uM
N-[6-oxo-6-[(3S,4S)-3-[(4-phenoxyphenyl)sulfonylamino]-4-sulfanylpyrrolidin-1-yl]hexyl]acetamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0040	uM
N-hydroxy-1-(pyridin-2-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0041	uM
(2R)-2-[(4-but-2-ynoxyphenyl)sulfonylamino]-4-(1,3-dioxoisoindol-2-yl)-N-hydroxybutanamide	473232: Inhibition of human recombinant MMP14 by fluorometric assay	ic50	0.0043	uM
4-[4-(3-chlorophenoxy)phenyl]sulfonyl-N-hydroxyoxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0045	uM
1-cyclopropyl-N-hydroxy-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0046	uM
(4R)-3-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-hydroxy-1,1-dioxo-1,3-thiazolidine-4-carboxamide	648199: Inhibition of MMP14 catalytic domain using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 1 hr prior substrate addition measured after 30 mins by spectrofluorimetry	ic50	0.0050	uM
N-[(3S,4S)-1-(6-aminohexanoyl)-4-sulfanylpyrrolidin-3-yl]-4-phenoxybenzenesulfonamide;hydrochloride	1937797: Inhibition of MMP14 (unknown origin) assessed as inhibition constant	ki	0.0050	uM
N-[[3-[4-[2-[formyl(hydroxy)amino]-3-methylbutyl]sulfonylphenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328783: Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0054	uM
4-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-hydroxyoxane-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0056	uM
(2R)-2-[(3S,4R)-1-[4-(1,3-dioxoisoindol-2-yl)butanoyl]-4-sulfanylpyrrolidin-3-yl]sulfanyl-4-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0060	uM
(2R)-2-[(3S,4R)-1-acetyl-4-sulfanylpyrrolidin-3-yl]sulfanyl-4-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0062	uM
1-cyclopropyl-4-[4-(4-ethoxyphenoxy)phenyl]sulfonyl-N-hydroxypiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0068	uM
1-N,3-N-bis[4-[2-[[(2R)-4-(1,3-dioxoisoindol-2-yl)-1-(hydroxyamino)-1-oxobutan-2-yl]-[4-(4-methoxyphenyl)phenyl]sulfonylamino]ethylamino]-4-oxobutyl]benzene-1,3-dicarboxamide	1574102: Inhibition of recombinant human MT1-MMP catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 3 hrs followed by substrate addition and measured every 10 secs for 15 min by fluorometric assay	ic50	0.0070	uM
(2R)-2-[(3S,4R)-1-[6-(1,3-dioxoisoindol-2-yl)hexanoyl]-4-sulfanylpyrrolidin-3-yl]sulfanyl-4-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide	747691: Inhibition of MMP-14 (unknown origin) using Mca-PLGLDpa-AR-NH2 as substrate preincubated for 30 mins by fluorescence assay	ki	0.0070	uM
1-benzyl-4-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-hydroxypiperidine-4-carboxamide	109565: Inhibition of Matrix metalloprotease-14	ic50	0.0070	uM
N-hydroxy-1-propan-2-yl-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0071	uM
N-hydroxy-1-(2-morpholin-4-ylethyl)-4-[4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604455: Inhibition of human MMP14 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0074	uM
4-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-N-hydroxyoxane-4-carboxamide	109566: Inhibition of matrix metalloprotease-14	ic50	0.0074	uM
(2R)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(pyridin-3-ylmethyl)amino]-3-methylbutanamide;hydrochloride	352557: Inhibition of MMP14	ic50	0.0075	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression, decreases reaction, decreases expression	5
Progesterone	decreases reaction, decreases expression, affects cotreatment, increases expression	5
sodium arsenite	decreases reaction, increases expression	4
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	4
Arsenic Trioxide	affects cotreatment, decreases expression, decreases reaction, increases expression, affects expression	3
Tetradecanoylphorbol Acetate	decreases reaction, increases expression	3
Genistein	decreases expression, increases expression	3
bisphenol A	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Manganese	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
biochanin A	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
carvone	decreases expression	1
glycidyl methacrylate	affects expression, increases expression	1
lead acetate	increases expression	1
piperine	decreases reaction, increases expression	1
salinomycin	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1

ChEMBL screening assays

274 unique, capped per target: 252 binding, 18 admet, 3 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001087	Binding	Ratio of kcat/km for human recombinant MMP14 assessed as drug cleavage	Development of an optimized activatable MMP-14 targeted SPECT imaging probe. — Bioorg Med Chem
CHEMBL2354273	Functional	PubChem BioAssay. SAR confirmation of uHTS hits for a small molecule inhibitors of MT1-MMP activation in a fluorescence assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3868406	ADMET	Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	Design, synthesis, and biological activity of novel, potent, and highly selective fused pyrimidine-2-carboxamide-4-one-based matrix metalloproteinase (MMP)-13 zinc-binding inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4T29	GM02295	Finite cell line	Female
CVCL_B1CE	Abcam A-431 MMP14 KO	Cancer cell line	Female
CVCL_D8QQ	Ubigene HCT 116 MMP14 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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