MMP17

Summary

MMP17 (matrix metallopeptidase 17, HGNC:7163) is a protein-coding gene on chromosome 12q24.33, encoding Matrix metalloproteinase-17 (Q9ULZ9). Endopeptidase that degrades various components of the extracellular matrix, such as fibrin.

This gene encodes a member of the peptidase M10 family and membrane-type subfamily 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. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein is unique among the membrane-type matrix metalloproteinases in that it is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Elevated expression of the encoded protein has been observed in osteoarthritis and multiple human cancers.

Source: NCBI Gene 4326 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 159 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016155

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7163
Approved symbol	MMP17
Name	matrix metallopeptidase 17
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	MT4-MMP
Ensembl gene	ENSG00000198598
Ensembl biotype	protein_coding
OMIM	602285
Entrez	4326

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000360564, ENST00000534865, ENST00000535004, ENST00000535291, ENST00000537848, ENST00000542142, ENST00000542648, ENST00000545671, ENST00000545790, ENST00000912510, ENST00000949084, ENST00000949085

RefSeq mRNA: 2 — MANE Select: NM_016155 NM_001411000, NM_016155

CCDS: CCDS31927, CCDS91781

Canonical transcript exons

ENST00000360564 — 10 exons

Exon	Start	End
ENSE00001222955	131849802	131850059
ENSE00001222987	131840573	131840856
ENSE00001291806	131850925	131851771
ENSE00001302203	131828393	131828653
ENSE00003537716	131845297	131845449
ENSE00003543633	131838612	131838741
ENSE00003611462	131843997	131844081
ENSE00003636521	131838195	131838327
ENSE00003682229	131841624	131841800
ENSE00003694334	131845118	131845200

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.6776 / max 65.8923, expressed in 1064 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128761	2.6776	1064

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	94.38	gold quality
anterior cingulate cortex	UBERON:0009835	93.85	gold quality
cingulate cortex	UBERON:0003027	93.80	gold quality
nucleus accumbens	UBERON:0001882	93.35	gold quality
prefrontal cortex	UBERON:0000451	91.66	gold quality
caudate nucleus	UBERON:0001873	91.18	gold quality
putamen	UBERON:0001874	90.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.83	gold quality
amygdala	UBERON:0001876	90.40	gold quality
granulocyte	CL:0000094	89.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.02	gold quality
neocortex	UBERON:0001950	87.91	gold quality
frontal cortex	UBERON:0001870	87.39	gold quality
tibial nerve	UBERON:0001323	87.17	gold quality
endocervix	UBERON:0000458	86.94	gold quality
left ovary	UBERON:0002119	86.79	gold quality
right ovary	UBERON:0002118	86.66	gold quality
stromal cell of endometrium	CL:0002255	86.62	gold quality
telencephalon	UBERON:0001893	86.13	gold quality
Brodmann (1909) area 10	UBERON:0013541	85.90	gold quality
cerebral cortex	UBERON:0000956	85.32	gold quality
ectocervix	UBERON:0012249	84.71	gold quality
monocyte	CL:0000576	84.51	gold quality
mononuclear cell	CL:0000842	84.20	gold quality
forebrain	UBERON:0001890	84.14	gold quality
hypothalamus	UBERON:0001898	84.06	gold quality
leukocyte	CL:0000738	84.01	gold quality
Ammon’s horn	UBERON:0001954	83.96	gold quality
cortical plate	UBERON:0005343	83.65	gold quality
brain	UBERON:0000955	81.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	213.58
E-ANND-3	no	2.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, IRF6, SNAI2

miRNA regulators (miRDB)

18 targeting MMP17, 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-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-7106-3P	97.33	65.33	644
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-1915-5P	95.25	65.78	571

Literature-anchored findings (GeneRIF, showing 19)

• down-regulation of most MT-MMPs is typical for prostate carcinoma; seems to occur mainly in epithelial cells (PMID:12661033)
• Data show that eosinophils constitutively express membrane type-4 matrix metalloproteinase (MT4-MMP), which is increased upon stimulation with tumor necrosis factor-alpha. (PMID:12962706)
• MT4-MMP and the proteoglycan form of syndecan-1 have roles in ADAMTS-4 activation on the cell surface (PMID:14701864)
• MT1-MT4-MMP chimaeras do not undergo normal trafficking and are not correctly processed to their fully active forms and, as a consequence, they are unable to activate pro-MMP-2 at the cell surface. (PMID:16686598)
• MT4-MMP promotes lung metastasis by disturbing the tumour vessel integrity and thereby facilitating tumour cell intravasation (PMID:19426156)
• Studies suggest a model of hypoxia induced metastasis through expression of HIF-1alpha, and SLUG regulation of MT4-MMP transcription. (PMID:20019845)
• The data presented here provide a new insight into the characteristics of MT4-MMP and highlight the common and distinct properties of the glycosylphosphatidylinositol-anchored membrane type-matrix metalloproteinases. (PMID:21828052)
• It identifies MT4-MMP as a key intrinsic tumor cell determinant that contributes to the elaboration of a permissive microenvironment for metastatic dissemination. (PMID:22262494)
• CAV1 when found in lipid rafts does not allow the metalloproteinase MT4-MMP to localize into the lipid rafts, affecting its expression in the cell and probably its activity which is translated into the metastasis-associated activities of these cells. (PMID:22674854)
• A functional link between MT4-MMP and the growth factor receptor EGFR. (PMID:25320013)
• Screening of patients with inherited thoracic aortic aneurysms and dissections identified a missense mutation (R373H) in the MMP17 gene that prevented the expression of the protease in human transfected cells. (PMID:25963716)
• The MT4-MMP is internalized by the clathrin-independent carriers/GPI-enriched early endosomal compartments pathway, a mechanism that differs from that responsible for the internalization of other membrane-type MMP members. (PMID:26663028)
• Low MT4-MMP expression is associated with erlotinib resistance in breast cancer. (PMID:28196064)
• Three forms of MT4-MMP with molecular masses of 45 kDa, 58 kDa and 69 kDa were detected. Further, we demonstrate that the 58 kDa form is the mature protein in the cell membrane, while the 69 kDa form is its precursor found in intracellular compartments. (PMID:28531887)
• MT4-MMP targeting may constitute a novel strategy to boost patrolling monocyte activity in early inflammation. (PMID:29500407)
• In breast cancer cells, the overexpression of MT4-MMP modulates the expression of microRNAs involved in several biological processes associated with tumor formation and progression and with clinical relevance. (PMID:30792164)
• MT4-MMP promotes invadopodia formation and cell motility in FaDu head and neck cancer cells. (PMID:31813546)
• Increased expression of MMP17 predicts poor clinical outcomes in epithelial ovarian cancer patients. (PMID:36042626)
• Elevated Plasma Levels of MT4-MMP and MT6-MMP; A New Observation in Patients with Thyroid Nodules. (PMID:38310435)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp17a	ENSDARG00000078915
mus_musculus	Mmp17	ENSMUSG00000029436
rattus_norvegicus	Mmp17	ENSRNOG00000023643
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), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-17 — Q9ULZ9 (reviewed: Q9ULZ9)

Alternative names: Membrane-type matrix metalloproteinase 4, Membrane-type-4 matrix metalloproteinase

All UniProt accessions (4): Q9ULZ9, F5GWR3, F5GZA7, F5H209

UniProt curated annotations — full annotation on UniProt →

Function. Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumor necrosis factor-alpha. May also be involved in tumoral process. Cleaves pro-TNF at the ‘74-Ala-|-Gln-75’ site. Not obvious if able to proteolytically activate progelatinase A. Does not hydrolyze collagen types I, II, III, IV and V, gelatin, fibronectin, laminin, decorin nor alpha1-antitrypsin.

Subcellular location. Cell membrane. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in brain, leukocytes, colon, ovary testis and breast cancer. Expressed also in many transformed and non-transformed cell types.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase.

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.

Similarity. Belongs to the peptidase M10A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULZ9-1	Long	yes
Q9ULZ9-2	Short, Puente

RefSeq proteins (2): NP_001397929, NP_057239* (*=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
IPR018487	Hemopexin-like_repeat	Repeat
IPR021190	Pept_M10A	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471

UniProt features (23 total): binding site 4, repeat 4, propeptide 2, glycosylation site 2, sequence conflict 2, region of interest 2, signal peptide 1, short sequence motif 1, active site 1, lipid moiety-binding region 1, disulfide bond 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULZ9-F1	77.85	0.51

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): 249

Ligand- & substrate-binding residues (4): 110 (in inhibited form); 248; 252; 258

Post-translational modifications (1): 565

Disulfide bonds (1): 332–523

Glycosylation sites (2): 137, 318

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 112 (showing top): GOBP_BEHAVIOR, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_206, MURAKAMI_UV_RESPONSE_1HR_UP, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, VERRECCHIA_DELAYED_RESPONSE_TO_TGFB1, RIZKI_TUMOR_INVASIVENESS_3D_UP, YAGI_AML_WITH_11Q23_REARRANGED, GOBP_FEEDING_BEHAVIOR, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS, chr12q24, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, YATGNWAAT_OCT_C, GOMF_PEPTIDASE_ACTIVITY

GO Biological Process (5): kidney development (GO:0001822), proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), drinking behavior (GO:0042756)

GO Molecular Function (8): metalloendopeptidase activity (GO:0004222), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), side of membrane (GO:0098552), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Degradation of the extracellular matrix	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
membrane	2
animal organ development	1
renal system development	1
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
feeding behavior	1
endopeptidase activity	1
metallopeptidase activity	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
cation binding	1
cell periphery	1
external encapsulating structure	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP17	TIMP1	P01033	658
MMP17	FURIN	P09958	638
MMP17	TIMP2	P16035	552
MMP17	SDC1	P18827	514
MMP17	TNF	P01375	508
MMP17	MMP14	P50281	464
MMP17	TIMP4	Q99727	461
MMP17	ADAMTS4	O75173	460
MMP17	MMP19	Q99542	451
MMP17	ADAMTS3	O15072	446
MMP17	TIMP3	P35625	428
MMP17	HPX	P02790	402
MMP17	ACAN	P16112	350
MMP17	FN1	P02751	349
MMP17	NNMT	P40261	346

IntAct

0 interactions, top by confidence:

BioGRID (6): MMP17 (Affinity Capture-RNA), MMP17 (Affinity Capture-RNA), MMP17 (Affinity Capture-MS), MMP17 (Negative Genetic), MMP24 (Negative Genetic), MMP17 (Negative Genetic)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, G7PWZ3, O77755, O88959, P0C0K7, P17490, P23276, P43021, P51882, P59509, P59996, P70505, Q02853, Q04912, Q04962, Q04997, Q0V8J4, Q0VAY3, Q17R55, Q3U435, Q499S5, Q4R7Z5, Q58Y75, Q62190, Q6MG64, Q76MJ5, Q7TN88, Q7Z442, Q80W65, Q8BMN4, Q8CJH3, Q8IVN8, Q8VCS0, Q91X21, Q96KR4, Q96PQ0, Q96S42

Diamond homologs: D0EM77, G5EBU3, O04529, O13065, O18733, O18767, O18927, O23507, O35548, O44836, O54732, O55123, O55761, O60882, O62806, O70138, O75900, O77656, O88272, O88676, O88766, O93470, P03956, P03957, P07152, P08253, P08254, P09237, P09238, P13943, P14780, P21692, P22757, P22894, P23097, P24347, P28053, P28862, P28863, P29136

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MMP17	up-regulates	ECM_disassembly
MMP17	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2725 predictions. Top by Δscore:

Variant	Effect	Δscore
12:131838609:CA:C	acceptor_loss	1.0000
12:131838610:A:AG	acceptor_gain	1.0000
12:131838610:AGAC:A	acceptor_gain	1.0000
12:131838611:G:GT	acceptor_gain	1.0000
12:131838611:GA:G	acceptor_gain	1.0000
12:131838611:GAC:G	acceptor_gain	1.0000
12:131838611:GACG:G	acceptor_gain	1.0000
12:131838611:GACGA:G	acceptor_gain	1.0000
12:131841620:CCAG:C	acceptor_loss	1.0000
12:131841621:CAGA:C	acceptor_loss	1.0000
12:131841622:A:AG	acceptor_gain	1.0000
12:131841623:G:GA	acceptor_loss	1.0000
12:131841623:G:GG	acceptor_gain	1.0000
12:131841623:GAT:G	acceptor_gain	1.0000
12:131844082:G:GG	donor_gain	1.0000
12:131845291:CCCCA:C	acceptor_loss	1.0000
12:131845292:CCCA:C	acceptor_loss	1.0000
12:131845294:CA:C	acceptor_loss	1.0000
12:131845295:A:AC	acceptor_loss	1.0000
12:131845296:GGCAA:G	acceptor_gain	1.0000
12:131845446:AAAG:A	donor_loss	1.0000
12:131845447:AAGGT:A	donor_loss	1.0000
12:131845448:AGGTG:A	donor_gain	1.0000
12:131845450:G:GA	donor_loss	1.0000
12:131845451:T:A	donor_loss	1.0000
12:131850056:GACG:G	donor_gain	1.0000
12:131850057:ACG:A	donor_gain	1.0000
12:131850057:ACGGT:A	donor_loss	1.0000
12:131850058:CG:C	donor_gain	1.0000
12:131850059:GG:G	donor_gain	1.0000

AlphaMissense

3892 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:131840649:T:A	W167R	0.998
12:131840649:T:C	W167R	0.998
12:131845308:T:A	W355R	0.998
12:131845308:T:C	W355R	0.998
12:131838737:T:A	W140R	0.997
12:131838737:T:C	W140R	0.997
12:131845161:G:C	A338P	0.997
12:131845368:T:A	W375R	0.997
12:131845368:T:C	W375R	0.997
12:131845370:G:C	W375C	0.997
12:131845370:G:T	W375C	0.997
12:131845404:G:C	A387P	0.997
12:131849810:T:G	Y405D	0.997
12:131838293:G:C	Q86H	0.996
12:131838293:G:T	Q86H	0.996
12:131840674:T:C	F175S	0.996
12:131840715:T:C	F189L	0.996
12:131840717:C:A	F189L	0.996
12:131840717:C:G	F189L	0.996
12:131840821:T:C	F224S	0.996
12:131845167:G:C	A340P	0.996
12:131845174:T:C	I342T	0.996
12:131845310:G:C	W355C	0.996
12:131845310:G:T	W355C	0.996
12:131838739:G:C	W140C	0.995
12:131838739:G:T	W140C	0.995
12:131840773:C:A	A208D	0.995
12:131840838:T:A	W230R	0.995
12:131840838:T:C	W230R	0.995
12:131841653:G:C	A246P	0.995

dbSNP variants (sampled 300 via entrez): RS1000281762 (12:131851145 C>T), RS1000523412 (12:131847279 G>A,T), RS1000617440 (12:131844593 G>A), RS1000671446 (12:131829456 GC>G,GCC), RS1000855605 (12:131848959 T>C), RS1000877957 (12:131835529 C>T), RS1001131256 (12:131848432 C>G), RS1001202628 (12:131840325 C>T), RS1001239209 (12:131843235 G>A), RS1001247193 (12:131847558 G>A), RS1001280557 (12:131846595 G>A), RS1001288978 (12:131846332 G>T), RS1001291057 (12:131828287 G>A,C), RS1001341729 (12:131852271 C>T), RS1001388640 (12:131838536 C>T)

Disease associations

OMIM: gene MIM:602285 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001563_10	Migraine	5.000000e-07
GCST004685_2	Psychosis proneness (perceptual aberration scale)	3.000000e-06
GCST005951_3	Body mass index	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008337	psychosis predisposition measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2937 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,065 (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
CHEMBL19611	ILOMASTAT	2	12,065

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
ilomastat	Inhibition	8.47	pIC50

Binding affinities (BindingDB)

5 measured of 9 human assays (9 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[(3-methyl-2-oxo-1-pyridinyl)methyl]-5-(4-phenoxyphenyl)imidazolidine-2,4-dione	IC50	29000 nM	US-10000476: Pyridone derivative, pharmaceutical containing the same and methods of use thereof
5-[(3-methyl-2-oxo-1-pyridinyl)methyl]-5-(3-pyridin-3-ylphenyl)imidazolidine-2,4-dione	IC50	31000 nM	US-10000476: Pyridone derivative, pharmaceutical containing the same and methods of use thereof
5-[4-(2-fluorophenoxy)phenyl]-5-[(3-methyl-2-oxo-1-pyridinyl)methyl]imidazolidine-2,4-dione	IC50	51000 nM	US-10000476: Pyridone derivative, pharmaceutical containing the same and methods of use thereof
5-(5-chloro-2-methoxyphenyl)-5-[(3-methyl-2-oxo-1-pyridinyl)methyl]imidazolidine-2,4-dione	IC50	62000 nM	US-10000476: Pyridone derivative, pharmaceutical containing the same and methods of use thereof
5-[4-[(4-fluorophenyl)methyl]phenyl]-5-[(3-methyl-2-oxo-1-pyridinyl)methyl]imidazolidine-2,4-dione	IC50	69000 nM	US-10000476: Pyridone derivative, pharmaceutical containing the same and methods of use thereof

ChEMBL bioactivities

18 potent at pChembl≥5 of 24 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.47	IC50	3.4	nM	ILOMASTAT
8.24	IC50	5.7	nM	CHEMBL3355722
7.61	IC50	24.7	nM	CHEMBL3355723
6.66	IC50	220	nM	CHEMBL431226
6.48	IC50	330	nM	CHEMBL329967
6.46	IC50	350	nM	CHEMBL99365
6.46	IC50	350	nM	CHEMBL98390
6.30	IC50	500	nM	CHEMBL328645
6.26	IC50	550	nM	CHEMBL95414
6.22	IC50	600	nM	CHEMBL319782
5.96	IC50	1100	nM	CHEMBL419896
5.70	IC50	2000	nM	CHEMBL328199
5.60	IC50	2500	nM	CHEMBL98852
5.52	IC50	3000	nM	CHEMBL99045
5.52	IC50	3000	nM	CHEMBL99995
5.49	IC50	3260	nM	CHEMBL3355724
5.40	IC50	4000	nM	CHEMBL318252
5.40	IC50	4000	nM	CHEMBL98202

PubChem BioAssay actives

18 with measured affinity, of 29 total; 18 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-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	359850: Inhibition of MMP17 catalytic domain	ic50	0.0034	uM
(2R)-N-[(2S)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	1172328: Inhibition of human recombinant ADAM17 using Mca-PLAQAV-Dpa-RSSSR-NH2	ic50	0.0057	uM
(2R)-N-[(2S)-1-[[(2S)-1-amino-6-[(4-fluorobenzoyl)amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-N’-hydroxy-2-(2-methylpropyl)butanediamide	1172328: Inhibition of human recombinant ADAM17 using Mca-PLAQAV-Dpa-RSSSR-NH2	ic50	0.0247	uM
N-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-2-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylethyl]-N-hydroxyformamide	109576: Inhibition of matrix metalloprotease-17	ic50	0.2200	uM
N-hydroxy-N-[1-(4-hydroxyiminocyclohexyl)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylpropan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	0.3300	uM
N-hydroxy-N-[1-[1-(2-methylpropyl)piperidin-4-yl]-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylpropan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	0.3500	uM
N-hydroxy-N-[1-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonyl-3-(4-oxocyclohexyl)propan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	0.3500	uM
N-hydroxy-N-[1-(4-hydroxyiminocyclohexyl)-2-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylethyl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	0.5000	uM
[4-[2-[formyl(hydroxy)amino]-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylpropylidene]piperidin-1-yl] 2,2-dimethylpropanoate	109576: Inhibition of matrix metalloprotease-17	ic50	0.5500	uM
N-hydroxy-N-[2-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonyl-1-(4-oxocyclohexyl)ethyl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	0.6000	uM
N-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylpropan-2-yl]-N-hydroxyformamide	109576: Inhibition of matrix metalloprotease-17	ic50	1.1000	uM
N-hydroxy-N-[1-(4-methylidenecyclohexyl)-2-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylethyl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	2.0000	uM
N-hydroxy-N-[1-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonyl-3-(4-oxocyclohexylidene)propan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	2.5000	uM
N-hydroxy-N-[1-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonyl-3-(oxan-4-ylidene)propan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	3.0000	uM
N-hydroxy-N-[1-(4-hydroxyiminocyclohexylidene)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylpropan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	3.0000	uM
[[(3R)-3-[[(2S)-1-[[(2S)-1-amino-6-[(4-fluorobenzoyl)amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]-5-methylhexanoyl]amino] 4-fluorobenzoate	1172328: Inhibition of human recombinant ADAM17 using Mca-PLAQAV-Dpa-RSSSR-NH2	ic50	3.2600	uM
N-hydroxy-N-[1-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonyl-3-(thian-4-ylidene)propan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	4.0000	uM
N-hydroxy-N-[1-[1-(2-methylpropyl)piperidin-4-ylidene]-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylpropan-2-yl]formamide	109576: Inhibition of matrix metalloprotease-17	ic50	4.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression, increases expression	3
Valproic Acid	increases expression, increases methylation	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
bisphenol F	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
aflatoxin B2	decreases methylation	1
abrine	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Estradiol	increases expression	1
Lead	affects expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tetrachloroethylene	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005429	Binding	Inhibition of MMP17 up to 100 uM	Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SY64	HAP1 MMP17 (-) 1	Cancer cell line	Male
CVCL_SY65	HAP1 MMP17 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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