MMP7

Summary

MMP7 (matrix metallopeptidase 7, HGNC:7174) is a protein-coding gene on chromosome 11q22.2, encoding Matrilysin (P09237). Degrades casein, gelatins of types I, III, IV, and V, and fibronectin.

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down proteoglycans, fibronectin, elastin and casein and differs from most MMP family members in that it lacks a conserved C-terminal hemopexin domain. The enzyme is involved in wound healing, and studies in mice suggest that it regulates the activity of defensins in intestinal mucosa. The gene is part of a cluster of MMP genes on chromosome 11. This gene exhibits elevated expression levels in multiple human cancers.

Source: NCBI Gene 4316 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 49 total
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002423

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7174
Approved symbol	MMP7
Name	matrix metallopeptidase 7
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Aliases	PUMP-1
Ensembl gene	ENSG00000137673
Ensembl biotype	protein_coding
OMIM	178990
Entrez	4316

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000260227, ENST00000531200, ENST00000533366, ENST00000896702, ENST00000896703

RefSeq mRNA: 1 — MANE Select: NM_002423 NM_002423

CCDS: CCDS8317

Canonical transcript exons

ENST00000260227 — 6 exons

Exon	Start	End
ENSE00000930296	102523240	102523401
ENSE00000930297	102524936	102525064
ENSE00001252223	102520508	102520804
ENSE00002145134	102530593	102530747
ENSE00003513714	102527757	102527983
ENSE00003683588	102527524	102527672

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.60.

FANTOM5 (CAGE): breadth broad, TPM avg 48.4986 / max 3895.9868, expressed in 382 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121977	48.3162	380
121978	0.1825	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	99.60	gold quality
islet of Langerhans	UBERON:0000006	99.04	gold quality
metanephros cortex	UBERON:0010533	98.05	gold quality
pancreatic ductal cell	CL:0002079	97.81	silver quality
epithelial cell of pancreas	CL:0000083	97.35	gold quality
type B pancreatic cell	CL:0000169	96.06	silver quality
caput epididymis	UBERON:0004358	95.13	gold quality
pancreas	UBERON:0001264	95.00	gold quality
body of pancreas	UBERON:0001150	94.52	gold quality
minor salivary gland	UBERON:0001830	91.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.32	gold quality
calcaneal tendon	UBERON:0003701	91.19	gold quality
epithelium of mammary gland	UBERON:0003244	90.83	silver quality
mammary duct	UBERON:0001765	90.60	silver quality
adult mammalian kidney	UBERON:0000082	90.31	gold quality
saliva-secreting gland	UBERON:0001044	89.79	gold quality
endometrium	UBERON:0001295	88.28	gold quality
amniotic fluid	UBERON:0000173	87.81	gold quality
skin of leg	UBERON:0001511	87.52	gold quality
right uterine tube	UBERON:0001302	87.51	gold quality
kidney	UBERON:0002113	86.96	gold quality
mammary gland	UBERON:0001911	86.62	gold quality
thoracic mammary gland	UBERON:0005200	86.61	gold quality
skin of abdomen	UBERON:0001416	86.26	gold quality
mouth mucosa	UBERON:0003729	85.86	gold quality
zone of skin	UBERON:0000014	85.31	gold quality
cortex of kidney	UBERON:0001225	84.97	gold quality
upper leg skin	UBERON:0004262	84.45	gold quality
palpebral conjunctiva	UBERON:0001812	83.81	silver quality
corpus epididymis	UBERON:0004359	83.00	silver quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	5303.40
E-GEOD-83139	yes	5082.47
E-MTAB-10855	yes	3600.68
E-MTAB-10283	yes	2901.66
E-MTAB-8410	yes	2498.66
E-HCAD-15	yes	2437.26
E-MTAB-5061	yes	2355.08
E-GEOD-75688	yes	2250.16
E-MTAB-9841	yes	2051.01
E-MTAB-8530	yes	1417.11
E-MTAB-10885	yes	1324.15
E-MTAB-8221	yes	1311.19
E-MTAB-10287	yes	51.69
E-CURD-114	yes	30.74
E-HCAD-1	yes	20.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ASCL1, CTNNB1, CTNND1, DNMT1, ETS1, ETV1, ETV4, FOS, FOXA2, FOXC1, FOXM1, GLI3, HNF1A, HNF1B, HNF4A, JUN, LEF1, MBIP, NCOA3, ONECUT1, SOX18, STAT1, STAT3, TCF7L2, TP53, ZBTB33

miRNA regulators (miRDB)

25 targeting MMP7, 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-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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-362-5P	95.87	66.02	554
HSA-MIR-500B-5P	95.87	66.04	557

Literature-anchored findings (GeneRIF, showing 40)

• MMP-7 activity is upregulated in colorectal cancer liver metastases (PMID:11801551)
• plays an important role not only in tumor metastasis but in micrometastasis to lymph node (PMID:11925859)
• Overexpression of MMP-7 is associated with invasiveness in gastric carcinoma (PMID:11927011)
• Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. (PMID:11983918)
• Immunoelectron microscopy revealed that matrix metalloproteinase-7 was expressed within basal laminar deposits and amorphous materials around the retinal pigment epithelial cells in age-related macular degeneration. (PMID:12005165)
• destruction of the surrounding matrix by endometriosis might be caused by various MMPs, which are mainly produced in stromal cells. (PMID:12034345)
• study of expression in ulcerative colitis related tumorigenesis (PMID:12112311)
• Cleavage of FasL by MMP-7 occurs at the leucine residues in sequence “ELAELR” within the region between the transmembrane and trimerization domains. When this site is unavailable, a “SL,” is cleaved. MMP-7 differentially processes murine and human FasL (PMID:12464266)
• increased expression of matrix metalloproteinase-7 is associated with high grade transitional cell carcinoma of the urinary bladder may be associated with tumor invasion and metastasis (PMID:12579270)
• Increased expression of MMP-7 in high grade renal cell carcinoma might be associated with tumor invasion and metastasis (PMID:12684625)
• In alveolar-like epithelial cells, transfection of activated matrilysin resulted in shedding of E-cadherin and accelerated cell migration. In vivo, matrilysin co-localized with E-cadherin at the basolateral surfaces of migrating tracheal epithelium. (PMID:12759241)
• findings suggest that local pericellular production of hypochlorous acid by phagocytes is a physiological mechanism for governing matrix metalloproteinase-7 activity during inflammation (PMID:12759346)
• MMP-7 is induced in human gastric epithelial cells infected with Helicobacter pylori; it has a role in epithelial cell migration (PMID:12808021)
• src oncogene signaling involves synergistic cooperation between the AP-1 and LEF-1 transcription factors in activation of the matrilysin promoter in colon cancer cells. (PMID:12958188)
• Data show that matrilysin confers macrophages with their most potent matrix metalloproteinase-dependent elastolytic system. (PMID:12963695)
• Down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma. (PMID:14516315)
• May contribute to the tumorigenesis of MMP-7-producing IGF-IR-expressing tumors in the primary site and to organ-specific metastasis in a paracrine manner (PMID:14744783)
• Heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. (PMID:15040016)
• matrix metalloproteinase-7 has a role in progression of pancreatic cancer (PMID:15102692)
• matrilysin may have a role in renal tubular injury and progression of tubulointerstitial fibrosis, and Wnt4 may regulate matrilysin expression in the kidney (PMID:15149334)
• the importance of MMP7 as a predictor of secondary Extramammary Paget’s disease or the putative origin of Paget’s cells from the dermal adenocarcinoma cells of apocrine duct origin (PMID:15239678)
• Overexpression of MMP-7 is associated with non-small cell lung cancer (PMID:15375490)
• These results indicate MMP-7 is overexpressed in malignant ovarian epithelium and suggest MMP-7 may facilitate tumor cell invasion in vivo partly through the induction of progelatinase activation. (PMID:15523695)
• alcohols are considered to bind the hydrophobic S1’ subsite most plausibly, and the size of the pocket was estimated to be large enough to accommodate the length of 1-butanol (4-carbon chain) and the bulk of tertiary alcohols (PMID:15618645)
• pattern of secretion in polarized MDCK cells expressing stably transfected human MMP-7 (PMID:15652345)
• Results imply that MMP-7 is a major MMP associated with the tissue remodeling during the progression of liver fibrosis in biliary atresia. (PMID:15696117)
• We assessed mRNA expression of MMPs in six human colorectal cancer cell lines and found a considerable level of MMP-7 expression in HT-29 cells. (PMID:15725655)
• results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7 (PMID:15800927)
• Activation of MMP-7 protein closely involved in disruption of tight junction structure and consequent induction of cell dissociation as well as invasion in pancreatic cancer (PMID:15809719)
• Some green tea catechins induce pro-MMP-7 production via O2- production and the activation of JNK1/2. (PMID:15860507)
• expression up-regulated in Helicobacter species-infected colon and bile duct epithelial cells and hepatocytes. (PMID:15866216)
• Polymorphism might be a candidate marker for predicting individuals who are at higher risk to certain tumors but might not be used to predict potential of lymphatic metastasis in various cancers. (PMID:15930031)
• sFasL and matrilysin are expressed in seminal plasma and have a role in regulation of the function of the Fas system (PMID:15979995)
• MMP7 immunoreactivity was present in only polymyositis not dermatomyositis (PMID:16097959)
• Study suggests that targeting matrilysin may have important therapeutic implications. (PMID:16115946)
• Increased expression of MMP-7 in high grade uterine endometrial carcinoma (UEC) may be associated with tumor invasion and metastasis, and MMP-7 could serve as a prognostic maker in UEC. (PMID:16142384)
• In chronic rhinosinusitis and nasal polyps tissues the expression of TGF-beta1, MMP-7, MMP-9, TIMP-1 protein was significant increased compared to controls. (PMID:16248458)
• shed syndecan-1 or MMP7-syndecan-1 complexes may have roles in tumor progression (PMID:16286510)
• The 181A/G polymorphism in MMP7 has a potential to be a susceptibility factor for endometriosis and adenomyosis. (PMID:16455621)
• Fas downregulation and a consequential increased resistance to FasL-triggered apoptosis resulting from upregulated MMP-7 in colorectal cancer cells could be a key mechanism for their escape from the immune surveillance (PMID:16474169)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp20a	ENSDARG00000089887
mus_musculus	Mmp7	ENSMUSG00000018623
rattus_norvegicus	Mmp7	ENSRNOG00000010507
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), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrilysin — P09237 (reviewed: P09237)

Alternative names: Matrin, Matrix metalloproteinase-7, Pump-1 protease, Uterine metalloproteinase

All UniProt accessions (1): P09237

UniProt curated annotations — full annotation on UniProt →

Function. Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Cofactor. Binds 2 calcium ions per subunit. Binds 2 Zn(2+) ions per subunit.

Domain organisation. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_002414* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001818	Pept_M10_metallopeptidase	Domain
IPR002477	Peptidoglycan-bd-like	Domain
IPR006026	Peptidase_Metallo	Domain
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

Pfam: PF00413, PF01471

Enzyme classification (BRENDA):

• EC 3.4.24.23 — matrilysin (BRENDA: 7 organisms, 173 substrates, 186 inhibitors, 24 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(7-METHOXYCOUMARIN-4-YL)ACETYL-LPRO-L-LEU-GLY-L-	0.0511–0.211	6
DANSYL-PLALWAR	0.0079–0.024	4
(7-METHOXYCOUMARIN-4-YL)-ACETYL-L-PRO-L-LEU-GLY-	0.019–0.057	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-L-PRO-LEU-GLY-L-L	0.028	1
2,4-DINITROPHENYL-ARG-PRO-LEU-ALA-LEU-TRP-ARG-SE	0.026	1
2,4-DINITROPHENYL-PRO-LEU-GLY-LEU-TRP-ALA-D-ARG	0.065	1
ENTACTIN	0.0009	1
GLY-PRO-GLN-ALA-ILE-ALA-GLY-GLN	0.81	1
GLY-PRO-GLN-GLY-ILE-ALA-GLY-GLN	2	1
GLY-PRO-GLN-GLY-ILE-ALA-MET-GLN	2.3	1
GLY-PRO-GLN-GLY-LEU-ALA-GLY-GLN	7.3	1
GLY-PRO-MET-GLY-ILE-ALA-GLY-GLN	4.2	1
PB-M7VIS	0.0005	1

UniProt features (53 total): binding site 18, strand 16, helix 8, sequence variant 3, turn 3, signal peptide 1, propeptide 1, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8JUG	X-RAY DIFFRACTION	1.3
8JUF	X-RAY DIFFRACTION	1.39
7WXX	X-RAY DIFFRACTION	1.5
8JUD	X-RAY DIFFRACTION	1.5
2Y6D	X-RAY DIFFRACTION	1.6
2Y6C	X-RAY DIFFRACTION	1.7
8K4Z	X-RAY DIFFRACTION	1.7
1MMQ	X-RAY DIFFRACTION	1.9
1MMP	X-RAY DIFFRACTION	2.3
1MMR	X-RAY DIFFRACTION	2.4
2DDY	SOLUTION NMR
2MZE	SOLUTION NMR
2MZH	SOLUTION NMR
2MZI	SOLUTION NMR
5UE2	SOLUTION NMR
5UE5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09237-F1	88.03	0.75

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): 215

Ligand- & substrate-binding residues (18): 171; 173; 175; 178; 185; 187; 189; 191; 193; 196; 214; 218 …

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-162582	Signal Transduction
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 246 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_172, AP1_01, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, chr11q22, MODULE_317, TERAMOTO_OPN_TARGETS_CLUSTER_6, GOBP_PEPTIDE_METABOLIC_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SNIJDERS_AMPLIFIED_IN_HEAD_AND_NECK_TUMORS, BACH2_01, MODULE_210

GO Biological Process (14): antibacterial peptide secretion (GO:0002779), antibacterial peptide biosynthetic process (GO:0002780), proteolysis (GO:0006508), membrane protein ectodomain proteolysis (GO:0006509), response to xenobiotic stimulus (GO:0009410), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), positive regulation of cell migration (GO:0030335), collagen catabolic process (GO:0030574), membrane protein intracellular domain proteolysis (GO:0031293), regulation of cell population proliferation (GO:0042127), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), defense response to bacterium (GO:0042742)

GO Molecular Function (9): 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 (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	2
Collagen formation	1
ESR-mediated signaling	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antibacterial peptide production	2
membrane protein proteolysis	2
defense response to bacterium	2
peptidase activity	2
endopeptidase activity	2
antimicrobial peptide secretion	1
antimicrobial peptide biosynthetic process	1
protein metabolic process	1
response to chemical	1
cellular component disassembly	1
extracellular matrix organization	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
cell population proliferation	1
regulation of cellular process	1
defense response	1
response to bacterium	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
cellular anatomical structure	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

2814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP7	TIMP2	P16035	932
MMP7	CD44	P16070	927
MMP7	TIMP1	P01033	912
MMP7	TIMP3	P35625	890
MMP7	CTNNB1	P35222	815
MMP7	MMP2	P08253	798
MMP7	MMP9	P14780	789
MMP7	SERPINE1	P05121	780
MMP7	FN1	P02751	777
MMP7	TP53	P04637	774
MMP7	SDC1	P18827	749
MMP7	SPP1	P10451	745
MMP7	PLAU	P00749	733
MMP7	MMP1	P03956	727
MMP7	IL1B	P01584	725

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MMP7	LGALS3	psi-mi:“MI:0570”(protein cleavage)	0.490
MMP7	LGALS3	psi-mi:“MI:0403”(colocalization)	0.490
ELN	MMP7	psi-mi:“MI:0194”(cleavage reaction)	0.440
MMP7	CNOT1	psi-mi:“MI:0914”(association)	0.350
FASLG	MMP7	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (63): CNOT3 (Affinity Capture-MS), CNOT10 (Affinity Capture-MS), CNOT1 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), MAEA (Affinity Capture-MS), RMND5A (Affinity Capture-MS), RANBP9 (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), CNOT2 (Affinity Capture-MS), RQCD1 (Affinity Capture-MS), CNOT8 (Affinity Capture-MS), GID4 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS)

ESM2 similar proteins: B9DFR3, C0LGE0, C0LGR6, D7SFH9, F4K5K4, O04084, O04523, O04529, O22187, O23507, O80623, O81301, P09237, P17801, P29136, P50280, P55032, Q10738, Q3E884, Q3E989, Q5XF51, Q6NPN4, Q6ZFR0, Q8GWW6, Q8L7I2, Q8RXQ1, Q8VYE5, Q8VYR3, Q8VZU3, Q94CB1, Q9FF77, Q9FID8, Q9FID9, Q9FJ06, Q9FLJ8, Q9FLW0, Q9FN92, Q9LHL6, Q9LK35, Q9LSR8

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

6 interactions.

A	Effect	B	Mechanism
MMP7	“up-regulates activity”	SPP1	cleavage
MMP7	“down-regulates quantity by destabilization”	HAPLN1	cleavage
MMP7	“down-regulates quantity by destabilization”	DCN	cleavage
MMP7	up-regulates	ECM_disassembly
MMP7	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

401 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102525061:TGAG:T	acceptor_gain	1.0000
11:102525065:C:CC	acceptor_gain	1.0000
11:102530592:CCTG:C	donor_loss	1.0000
11:102523269:T:TA	donor_gain	0.9900
11:102524931:TATA:T	donor_loss	0.9900
11:102524932:ATAC:A	donor_loss	0.9900
11:102524933:TACC:T	donor_loss	0.9900
11:102524934:A:C	donor_loss	0.9900
11:102524935:C:CG	donor_loss	0.9900
11:102524965:T:TA	donor_gain	0.9900
11:102525060:ATGAG:A	acceptor_gain	0.9900
11:102525061:TGAGC:T	acceptor_loss	0.9900
11:102525062:GAG:G	acceptor_gain	0.9900
11:102525063:AG:A	acceptor_gain	0.9900
11:102525064:GC:G	acceptor_loss	0.9900
11:102525066:T:G	acceptor_loss	0.9900
11:102527522:ACCT:A	donor_gain	0.9900
11:102527523:CCTC:C	donor_gain	0.9900
11:102527668:CGATC:C	acceptor_gain	0.9900
11:102530591:A:AC	donor_gain	0.9900
11:102530592:C:CC	donor_gain	0.9900
11:102524939:G:C	donor_gain	0.9800
11:102527518:TCTTA:T	donor_loss	0.9800
11:102527519:CTTAC:C	donor_loss	0.9800
11:102527520:TTA:T	donor_loss	0.9800
11:102527521:TACC:T	donor_loss	0.9800
11:102527522:AC:A	donor_loss	0.9800
11:102527523:C:CG	donor_loss	0.9800
11:102527572:T:A	donor_gain	0.9800
11:102527669:GATCC:G	acceptor_loss	0.9800

AlphaMissense

1736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102527534:A:C	F158L	0.993
11:102527534:A:T	F158L	0.993
11:102527536:A:G	F158L	0.993
11:102525009:A:C	F180L	0.989
11:102525009:A:T	F180L	0.989
11:102525011:A:G	F180L	0.989
11:102525042:A:C	F169L	0.989
11:102525042:A:T	F169L	0.989
11:102525044:A:G	F169L	0.989
11:102524955:C:A	W198C	0.987
11:102524955:C:G	W198C	0.987
11:102527600:C:A	W136C	0.987
11:102527600:C:G	W136C	0.987
11:102527602:A:G	W136R	0.984
11:102527602:A:T	W136R	0.984
11:102527780:C:A	W104C	0.984
11:102527780:C:G	W104C	0.984
11:102524957:A:G	W198R	0.982
11:102524957:A:T	W198R	0.982
11:102523343:A:C	H224Q	0.981
11:102523343:A:T	H224Q	0.981
11:102527782:A:G	W104R	0.980
11:102527782:A:T	W104R	0.980
11:102523327:C:G	A230P	0.979
11:102525043:A:C	F169C	0.979
11:102524974:A:G	F192S	0.978
11:102523361:A:C	H218Q	0.977
11:102523361:A:T	H218Q	0.977
11:102523370:T:A	E215D	0.974
11:102523370:T:G	E215D	0.974

dbSNP variants (sampled 300 via entrez): RS1000079990 (11:102529973 C>A,T), RS1000302078 (11:102520285 G>T), RS1000381022 (11:102531716 T>C), RS1000909777 (11:102528823 C>T), RS1000962032 (11:102522937 A>G), RS1001124867 (11:102529073 T>A), RS1001305215 (11:102524770 G>A), RS1002467841 (11:102528392 A>G), RS1002630743 (11:102523845 G>A), RS1002975782 (11:102525815 A>G), RS1003136984 (11:102531936 A>C), RS1003208466 (11:102521013 C>A,G,T), RS1003268783 (11:102520284 G>T), RS1003311041 (11:102527147 A>G), RS1003914479 (11:102529576 T>C)

Disease associations

OMIM: gene MIM:178990 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001942_2	Prostate cancer	2.000000e-11
GCST003542_184	Night sleep phenotypes	7.000000e-07
GCST004093_37	Prostate-specific antigen levels	8.000000e-12
GCST006585_591	Blood protein levels	5.000000e-21

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4073 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 213,168 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200699	DOXYCYCLINE	4	93,821
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL75094	PRINOMASTAT	3	8,839
CHEMBL115653	CIPEMASTAT	2	359
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL2107228	SOLIMASTAT	2	104
CHEMBL279786	BATIMASTAT	2	21,247
CHEMBL440498	CTS-1027	2	615
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
RS 39066	Inhibition	9.64	pIC50
SL422	Inhibition	9.1	pKi
ilomastat	Inhibition	8.29	pIC50
marimastat	Inhibition	7.8	pIC50
doxycycline	Inhibition	4.14	pKd

Binding affinities (BindingDB)

41 measured of 67 human assays (68 total across all organisms); most potent 41 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
2-{4-(but-2-yn-1-yloxy)benzenesulfonamido}-N-hydroxyacetamide	KI	27 nM
MMP Inhibitor, 2	IC50	66 nM
(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-amino-4-[[(2S)-4-carboxy-2-[3-(4-thiophen-2-ylphenyl)propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	142 nM	US-8691753
RXP470, Compound 4	KI	192 nM
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-[4-(4-phenylthiophen-2-yl)phenyl]propanoylamino]pentanoic acid	KI	339 nM	US-8691753
(4S)-5-amino-5-oxo-4-[3-[4-(4-phenylthiophen-2-yl)phenyl]propanoylamino]pentanoic acid	KI	377 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	386 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[[(2R)-2-(carboxymethyl)-3-[4-(4-phenylthiophen-2-yl)phenyl]propanoyl]amino]butanoyl]amino]-5-oxopentanoic acid	KI	401 nM	US-8691753
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-(4-phenylphenyl)propanoylamino]butanoyl]amino]pentanoic acid	KI	445 nM	US-8691753
(2R)-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-2-[[4-(trifluoromethyl)phenyl]methyl]butanamide	IC50	704 nM	US-9206139: Aggrecanase inhibitors
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-(3-phenyl-1,2-oxazol-5-yl)propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	756 nM	US-8691753
(4R)-5-amino-4-[[(2S)-4-carboxy-2-[3-[4-(4-phenylthiophen-2-yl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	1060 nM	US-8691753
3-{[4-(but-2-yn-1-yloxy)benzene]sulfonyl}propane-1-thiol	KI	1300 nM
(3S,4S)-3-N-hydroxy-4-N-{4-[(2-methyl-1-benzofuran-3-yl)methyl]benzene}pyrrolidine-3,4-dicarboxamide	KI	1370 nM
(2R)-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-2-methyl-3-[4-(trifluoromethyl)phenyl]propanamide	IC50	1750 nM	US-9206139: Aggrecanase inhibitors
(3S,4S)-3-N-hydroxy-4-N-{4-[(2-methyl-1H-indol-3-yl)methyl]benzene}-1-(prop-2-yn-1-yl)pyrrolidine-3,4-dicarboxamide	KI	2930 nM
(3R,4R)-4-N-{4-[(2-ethyl-1H-indol-3-yl)methyl]benzene}-3-N-hydroxyoxane-3,4-dicarboxamide	KI	3300 nM
N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-2,2-dimethyl-3-[4-(trifluoromethyl)phenyl]propanamide	IC50	4650 nM	US-9206139: Aggrecanase inhibitors
(3R)-1-{[4-(but-2-yn-1-yloxy)benzene]sulfonyl}pyrrolidine-3-thiol	KI	5000 nM
4-(but-2-yn-1-yloxy)-N-methyl-N-(2-sulfanylethyl)benzene-1-sulfonamide	KI	5700 nM
US10414797, Comparative Example 17	IC50	6100 nM	US-10414797: Gelatinase inhibitors and use thereof
Gallic Acid, F	IC50	14000 nM
Guanosine Diphosphate	IC50	24000 nM
(2S)-2-cyclopropyl-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-3-[4-(trifluoromethyl)phenyl]propanamide	IC50	35000 nM	US-9206139: Aggrecanase inhibitors
(1S,5S,7R)-3-N-hydroxy-7-N-[(4-phenylphenyl)methyl]-6,8-dioxa-3-azabicyclo[3.2.1]octane-3,7-dicarboxamide	IC50	778000 nM
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-1-(2-propylpentanoyl)pyrrolidine-2-carboxamide	IC50	3.65e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)-1-butanoyl-N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-pyrrolidine-2-carboxamide	IC50	4.73e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)-1-acetyl-N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-pyrrolidine-2-carboxamide	IC50	4.94e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)-1-[(2S)-2-[[(2S)-2-[butanoyl(methyl)amino]-3-(1H-indol-3-yl)propanoyl]-methyl-amino]-4-methyl-pentanoyl]-N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-pyrrolidine-2-carboxamide	IC50	6.07e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-4,4-difluoro-N-methyl-1-(4-phenoxybutanoyl)pyrrolidine-2-carboxamide	IC50	6.61e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-1-(3-methylbutanoyl)pyrrolidine-2-carboxamide	IC50	6.68e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-1-hexanoyl-N-methyl-pyrrolidine-2-carboxamide	IC50	6.82e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2 S)-1-[(2S)-2-[acetyl(methyl)amino]-3-phenyl-propanoyl]-N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-pyrrolidine-2-carboxamide	IC50	9.13e+06 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-benzamido-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-1-hexanoyl-pyrrolidine-2-carboxamide	IC50	1.08e+07 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-1-(4-phenoxybutanoyl)pyrrolidine-2-carboxamide	IC50	1.14e+07 nM	US-10414797: Gelatinase inhibitors and use thereof
(2 S)-1-[(2S)-2-[acetyl(methyl)amino]propanoyl]-N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-pyrrolidine-2-carboxamide	IC50	1.49e+07 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-4,4-difluoro-1-hexanoyl-N-methyl-pyrrolidine-2-carboxamide	IC50	2.47e+07 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)—N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-1-octanoyl-pyrrolidine-2-carboxamide	IC50	2.56e+07 nM	US-10414797: Gelatinase inhibitors and use thereof
(2S)-1-[3-[acetyl(methyl)amino]propanoyl]-N-[(1S)-1-[[(1S)-3-[(3,5-difluorobenzoyl)amino]-1-(hydroxycarbamoyl)propyl]carbamoyl]-2-methyl-butyl]-N-methyl-pyrrolidine-2-carboxamide	IC50	2e+08 nM	US-10414797: Gelatinase inhibitors and use thereof

ChEMBL bioactivities

545 potent at pChembl≥5 of 636 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	IC50	0.06	nM	CHEMBL5574207
9.92	IC50	0.12	nM	CHEMBL5590289
9.89	IC50	0.13	nM	CHEMBL5575564
9.77	IC50	0.17	nM	CHEMBL5590711
9.77	IC50	0.17	nM	CHEMBL5573957
9.77	IC50	0.17	nM	CHEMBL5575333
9.77	IC50	0.17	nM	CHEMBL5584155
9.70	IC50	0.2	nM	CHEMBL5572317
9.66	IC50	0.22	nM	CHEMBL5572421
9.64	IC50	0.23	nM	CHEMBL288896
9.60	IC50	0.25	nM	CHEMBL5573293
9.59	IC50	0.26	nM	CHEMBL5569043
9.59	IC50	0.26	nM	CHEMBL5570298
9.52	IC50	0.3	nM	CHEMBL321180
9.49	IC50	0.32	nM	CHEMBL5575734
9.30	IC50	0.5	nM	CHEMBL5570760
9.11	IC50	0.78	nM	CHEMBL111798
9.10	Ki	0.8	nM	CHEMBL88520
9.02	IC50	0.96	nM	CHEMBL5567332
9.00	IC50	1	nM	CHEMBL40351
9.00	IC50	1	nM	CHEMBL40237
8.96	IC50	1.1	nM	CHEMBL432397
8.92	IC50	1.2	nM	CHEMBL324664
8.82	Ki	1.5	nM	CHEMBL91636
8.82	IC50	1.5	nM	CHEMBL325940
8.80	IC50	1.6	nM	CHEMBL65159
8.80	IC50	1.6	nM	CHEMBL418292
8.80	IC50	1.6	nM	CHEMBL5590933
8.77	IC50	1.7	nM	CHEMBL5416269
8.72	IC50	1.9	nM	CHEMBL5432095
8.70	IC50	2	nM	CHEMBL296874
8.66	IC50	2.2	nM	CHEMBL432991
8.66	IC50	2.2	nM	CHEMBL111736
8.62	IC50	2.4	nM	BATIMASTAT
8.60	IC50	2.5	nM	CHEMBL66134
8.59	IC50	2.6	nM	CHEMBL62007
8.55	IC50	2.8	nM	CHEMBL64013
8.55	IC50	2.8	nM	CHEMBL5417105
8.55	IC50	2.8	nM	CHEMBL5403802
8.52	Ki	3	nM	CHEMBL281795
8.52	IC50	3	nM	CHEMBL45631
8.51	IC50	3.1	nM	CHEMBL41497
8.51	IC50	3.1	nM	CHEMBL324874
8.48	IC50	3.3	nM	CHEMBL325552
8.44	IC50	3.6	nM	CHEMBL111104
8.42	IC50	3.8	nM	CHEMBL5426536
8.40	EC50	4	nM	CHEMBL187523
8.40	Ki	4	nM	CHEMBL87786
8.39	IC50	4.1	nM	MARIMASTAT
8.38	IC50	4.2	nM	CHEMBL303298

PubChem BioAssay actives

529 with measured affinity, of 1071 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[(2S)-2-[[(2S)-2-[[2-[[(4S)-4-carboxy-4-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]butanoyl]amino]acetyl]amino]-3-pyridin-4-ylpropanoyl]amino]-3,3-dimethylbutanoyl]amino]benzoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0001	uM
(2S)-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[(2S)-2,4-diaminobutanoyl]piperazine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0001	uM
(2S)-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[(2S)-2,6-diaminohexanoyl]piperazine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0001	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[[(2R)-6-amino-1-[(3S)-3-aminopyrrolidin-1-yl]-1-oxohexan-2-yl]carbamoyl]piperidine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0002	uM
(2S)-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[(2S)-2,3-diaminopropanoyl]piperazine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0002	uM
(2S)-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[(2S)-2,5-diaminopentanoyl]piperazine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0002	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[(4-aminopiperidin-4-yl)methylcarbamoyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0002	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[[(2R)-6-amino-1-(2-aminoethylamino)-1-oxohexan-2-yl]carbamoyl]piperidine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0002	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[[(2R)-1-(2-aminoethylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]piperidine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0002	uM
(2S,3R)-N,2-dihydroxy-N’-[(2S)-1-(1H-indol-3-yl)-3,3-dimethyl-1-oxobutan-2-yl]-3-(2-methylpropyl)butanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0003	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-(4-carbamoylanilino)-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0003	uM
(2S)-5-[[2-[[(2R)-1-[[(2S)-1-[4-(1-azabicyclo[2.2.2]octan-2-ylcarbamoyl)anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-2-methyl-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0003	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[(2S)-2-(3-aminopropanoylamino)-6-(dimethylamino)hexanoyl]piperazine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0003	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[4-[[(2R)-6-amino-1-[(2S,4S)-4-amino-2-carbamoylpyrrolidin-1-yl]-1-oxohexan-2-yl]carbamoyl]piperidine-1-carbonyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0003	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-[(1-aminocyclopropyl)methylcarbamoyl]anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0005	uM
(6S,7R,10S)-6-N-hydroxy-10-N-[2-(methylamino)-2-oxoethyl]-7-(2-methylpropyl)-8-oxo-2-oxa-9-azabicyclo[10.2.2]hexadeca-1(14),12,15-triene-6,10-dicarboxamide	107835: Inhibition of matrix metalloprotease-7	ki	0.0008	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(1H-indol-3-yl)-3,3-dimethyl-1-oxobutan-2-yl]-3-(2-methylpropyl)-2-prop-2-enylbutanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0008	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[4-(1-azabicyclo[2.2.2]octan-3-ylcarbamoyl)anilino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0010	uM
(2S,3R)-N,2-dihydroxy-N’-[(2S)-1-(1H-indol-3-yl)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)butanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0011	uM
(2S,3R)-N-hydroxy-3-(2-methylpropyl)-N’-[(2S)-1-oxo-3-phenyl-1-(1H-pyrrol-2-yl)propan-2-yl]-2-prop-2-enylbutanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0012	uM
(7S,8R,11S)-N-hydroxy-11-[4-(hydroxymethyl)benzoyl]-8-(2-methylpropyl)-9-oxo-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7-carboxamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0015	uM
(8S,11R,12S)-12-N-hydroxy-11-(2-methylpropyl)-8-N-(2-morpholin-4-yl-2-oxoethyl)-2,10-dioxo-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxamide	107835: Inhibition of matrix metalloprotease-7	ki	0.0015	uM
(7S,8R,11S)-7-N-hydroxy-11-N-methyl-8-(2-methylpropyl)-9-oxo-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0016	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-(carboxymethyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2098651: Inhibition of recombinant human MMP7 assessed as enzyme activity by measuring fluorescence using fluorogenic peptide substrate	ic50	0.0016	uM
(7S,8R,11S)-7-N-hydroxy-8-(2-methylpropyl)-9-oxo-11-N-pyridin-2-yl-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0016	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-3-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2020369: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr-(Dnp)-Ala-Arg-NH2 as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis	ic50	0.0017	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-2-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2020369: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr-(Dnp)-Ala-Arg-NH2 as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis	ic50	0.0019	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(1H-indol-3-yl)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-prop-2-enylbutanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0022	uM
(8S,9R,12S)-12-benzoyl-N-hydroxy-9-(2-methylpropyl)-10-oxo-2-oxa-11-azabicyclo[12.2.2]octadeca-1(16),14,17-triene-8-carboxamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0022	uM
(2S,3R)-N-hydroxy-N’-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-3-(2-methylpropyl)-2-(thiophen-2-ylsulfanylmethyl)butanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0024	uM
(7S,8R,11S)-7-N-hydroxy-8-(2-methylpropyl)-11-N-(2-methylsulfanylethyl)-9-oxo-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0025	uM
(8S,9R,12S)-8-N-hydroxy-12-N-methyl-9-(2-methylpropyl)-10-oxo-2-oxa-11-azabicyclo[12.2.2]octadeca-1(16),14,17-triene-8,12-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0026	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2020369: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr-(Dnp)-Ala-Arg-NH2 as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis	ic50	0.0028	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-pyridazin-4-ylpropan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2020369: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr-(Dnp)-Ala-Arg-NH2 as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis	ic50	0.0028	uM
(7S,8R,11S)-7-N-hydroxy-11-N-methyl-8-[3-(4-methylphenyl)propyl]-9-oxo-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0028	uM
(6S,7R,10S)-6-N-hydroxy-10-N-methyl-7-(2-methylpropyl)-8-oxo-2-oxa-9-azabicyclo[10.2.2]hexadeca-1(14),12,15-triene-6,10-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0030	uM
(8S,9R,12S)-N-hydroxy-12-(1H-indole-3-carbonyl)-9-(2-methylpropyl)-10-oxo-2-oxa-11-azabicyclo[12.2.2]octadeca-1(16),14,17-triene-8-carboxamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0031	uM
(7S,8R,11S)-11-benzoyl-N-hydroxy-8-(2-methylpropyl)-9-oxo-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7-carboxamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0033	uM
(2S,3R)-N-hydroxy-3-(2-methylpropyl)-N’-[(2S)-1-oxo-1,3-diphenylpropan-2-yl]-2-prop-2-enylbutanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0036	uM
(2S)-5-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-(2-amino-2-oxoethyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl]amino]-2-oxoethyl]amino]-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]-5-oxopentanoic acid	2020369: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr-(Dnp)-Ala-Arg-NH2 as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis	ic50	0.0038	uM
[2-[(1,3-diamino-1-oxopropan-2-yl)-(2,4-dinitrophenyl)carbamoyl]-4-phenylbutyl]-[2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid	107832: Inhibition of Matrix metalloprotease-7 Matrilysin	ki	0.0040	uM
(2S)-2-[[4-[4-(1-benzofuran-2-carbonylamino)phenyl]phenyl]sulfonylamino]-3-methylbutanoic acid	246031: Inhibitory concentration against MMP-7	ec50	0.0040	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	107840: Inhibition of Matrix metalloprotease-7 (MMP-7) in fluorimetric assay	ic50	0.0041	uM
(7S,8R,11S)-11-N-[2-(dimethylamino)ethyl]-7-N-hydroxy-8-(2-methylpropyl)-9-oxo-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,11-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0042	uM
(7S,8R,11S)-N-hydroxy-8-(2-methylpropyl)-9-oxo-11-(1H-pyrrole-2-carbonyl)-2-oxa-10-azabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7-carboxamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0042	uM
(2S,3R)-N-hydroxy-3-(2-methylpropyl)-N’-[(2S)-1-(1,3-oxazol-2-yl)-1-oxo-3-phenylpropan-2-yl]-2-prop-2-enylbutanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0042	uM
(2R)-N’-hydroxy-N-[(2S)-1-(1H-indol-3-yl)-1-oxo-3-phenylpropan-2-yl]-2-(2-methylpropyl)butanediamide	104928: In vitro inhibitory activity against human recombinant matrix metalloprotease 7	ic50	0.0043	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-oxo-1-(pyridin-2-ylamino)butan-2-yl]-N’-hydroxy-3-methoxy-2-(2-methylpropyl)butanediamide	1863877: Inhibition of MMP-7 (unknown origin)	ic50	0.0050	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	1912268: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay	ic50	0.0051	uM
(9S,10R,13S)-9-N-hydroxy-13-N-methyl-10-(2-methylpropyl)-11-oxo-2-oxa-12-azabicyclo[13.2.2]nonadeca-1(17),15,18-triene-9,13-dicarboxamide	104907: Inhibition of fibroblast matrilysin (MMP-7)	ic50	0.0057	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases reaction, decreases expression, decreases reaction, increases expression	4
Arsenic Trioxide	decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Quercetin	affects cotreatment, increases expression, decreases expression	3
Tobacco Smoke Pollution	decreases expression, decreases secretion, increases expression	3
sodium arsenite	decreases expression, increases expression	2
perfluorooctanoic acid	affects cotreatment, increases expression, decreases expression	2
andrographolide	decreases activity, decreases expression	2
Resveratrol	affects reaction, decreases reaction, increases expression, decreases expression	2
Curcumin	decreases reaction, increases expression	2
Estradiol	affects cotreatment, decreases expression, decreases secretion, increases secretion	2
Gallic Acid	decreases reaction, increases expression, decreases expression	2
Nicotine	affects reaction, affects response to substance, increases expression, increases reaction, decreases reaction	2
Plant Extracts	decreases reaction, increases expression, increases abundance	2
Progesterone	affects cotreatment, decreases expression, decreases secretion, decreases reaction	2
Silicon Dioxide	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
Tretinoin	decreases reaction, increases expression	2
Cadmium Chloride	increases expression, increases secretion	2
aristolochic acid I	decreases expression	1
ferric oxide	increases expression	1
thymoquinone	decreases expression	1
bufotalin	decreases reaction, increases expression	1
bisphenol A	increases expression	1
nobiletin	decreases expression	1
titanium dioxide	increases expression	1
mangiferin	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
arsenite	increases expression, decreases reaction	1
ergosta-4,6,8(14),22-tetraen-3-one	decreases reaction, increases expression	1

ChEMBL screening assays

220 unique, capped per target: 210 binding, 9 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001177	Binding	Inhibition of MMP7	Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3’ pocket. — Bioorg Med Chem Lett
CHEMBL4000932	ADMET	Inhibition of APMA-activated recombinant human MMP-7 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
CHEMBL838107	Functional	Inhibitory concentration against MMP-7	Identification of potent and selective MMP-13 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7V7	Ubigene A-549 MMP7 KO	Cancer cell line	Male
CVCL_F0RJ	A549 MMP7 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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