MMP13

Summary

MMP13 (matrix metallopeptidase 13, HGNC:7159) is a protein-coding gene on chromosome 11q22.2, encoding Collagenase 3 (P45452). Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN.

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 protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11.

Source: NCBI Gene 4322 — RefSeq curated summary.

At a glance

• Gene–disease (curated): metaphyseal chondrodysplasia, Spahr type (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 305 total — 9 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002427

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7159
Approved symbol	MMP13
Name	matrix metallopeptidase 13
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Aliases	CLG3
Ensembl gene	ENSG00000137745
Ensembl biotype	protein_coding
OMIM	600108
Entrez	4322

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000260302, ENST00000340273, ENST00000857540

RefSeq mRNA: 1 — MANE Select: NM_002427 NM_002427

CCDS: CCDS8324

Canonical transcript exons

ENST00000260302 — 10 exons

Exon	Start	End
ENSE00000930340	102945646	102945749
ENSE00000930341	102947891	102948050
ENSE00000930342	102949025	102949158
ENSE00000930343	102950110	102950227
ENSE00001105386	102955252	102955493
ENSE00001105391	102955586	102955732
ENSE00001105398	102954156	102954281
ENSE00001105401	102954458	102954606
ENSE00001139473	102952012	102952173
ENSE00002188786	102942995	102944366

Expression profiles

Bgee: expression breadth broad, 62 present calls, max score 99.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9865 / max 707.2177, expressed in 175 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122030	1.9865	175

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.19	gold quality
cartilage tissue	UBERON:0002418	97.94	gold quality
tibia	UBERON:0000979	96.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.53	gold quality
trabecular bone tissue	UBERON:0002483	65.82	gold quality
buccal mucosa cell	CL:0002336	63.21	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.69	gold quality
calcaneal tendon	UBERON:0003701	59.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	58.84	gold quality
decidua	UBERON:0002450	56.55	gold quality
endometrium epithelium	UBERON:0004811	55.00	gold quality
gingiva	UBERON:0001828	54.80	gold quality
cochlea	UBERON:0001844	54.38	silver quality
tendon	UBERON:0000043	53.51	gold quality
nasal cavity epithelium	UBERON:0005384	53.02	gold quality
bone element	UBERON:0001474	53.00	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
nasal cavity mucosa	UBERON:0001826	51.78	gold quality
tendon of biceps brachii	UBERON:0008188	50.89	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
gingival epithelium	UBERON:0001949	50.14	silver quality
quadriceps femoris	UBERON:0001377	49.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.68	gold quality
oviduct epithelium	UBERON:0004804	49.51	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	18317.59
E-MTAB-6653	yes	650.82
E-ANND-3	no	4.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, BMP7, CEBPB, CITED2, CREB1, CTNNB1, ELF3, ELK1, EPAS1, ERG, ESR1, ESR2, ETS1, ETS2, ETV4, FGF2, FOS, FOSL1, FOSL2, GLI1, GLI2, HDAC4, HDAC9, HES1, IGF1, ING2, JUN, JUNB, JUND, KAT7, LEF1, MAF, MAFB, MBIP, NFKB1, NFKB, NR4A2, POU5F1, PPARG

miRNA regulators (miRDB)

55 targeting MMP13, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-12123	99.52	71.79	2990

Literature-anchored findings (GeneRIF, showing 40)

• AGRE site plays a rate-limiting role in human collagenase-3 production. (PMID:11883937)
• Investigation of the role of Endo180/urokinase-type plasminogen activator receptor-associated protein as a collagenase 3 (matrix metalloproteinase 13) receptor (PMID:11903048)
• involvement of MAPKs, AP-1 and NF-kappa B transcription factors in the IL-1 induction of MMPs in chondrocytes (PMID:12009331)
• Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by mechanical strain in MH7A rheumatoid synovial cells (PMID:12009332)
• REVIEW: The structure, regulation, and function of human matrix metalloproteinase-13 (PMID:12139441)
• Data show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. (PMID:12192005)
• induction by transforming growth factor-beta via activation of p38 mitogen-activated protein kinase pathway (PMID:12270924)
• Two new MMP13 promoter polymorphisms. Genotype for one MMP13 polymorphism associated with fibrous plaque in black males. MMP13 expressed in all layers of aorta. Polymorphism a functional variant. Genetic risk factor for extent of fibrous plaque. (PMID:12392760)
• translational repression by an alternatively spliced form of T-cell-restricted intracellular antigen-related protein (PMID:12426321)
• MMP13 expression is regulated by IGF-1 and OP-1 (PMID:12734180)
• induction of the MMP-13 gene by TNF-alpha is mediated by ERK, p38, and JNK MAP kinases as well as AP-1 and NF-kappaB transcription factors (PMID:12878172)
• Together with other prognostic markers, determination of MMP-13 in ascitic fluid may help to identify patients at risk for early death and help to individualize adjuvant therapy (PMID:12974393)
• catabolic role of ET-1 in osteoarthritis cartilage via MMP-1 and MMP-13 up-regulation. (PMID:14558091)
• MMP-13, uPA, and PAI-1 antigen levels were determined in the synovium of patients with osteoarthritis (PMID:15067375)
• MMP13 is upregulated in breast cancer (PMID:15551360)
• MMP-1 and MMP-3 secretion by gastric epithelial cells are differentially regulated by E prostaglandins and MAPKs (PMID:15640153)
• gene expression regulation in Lyme disease (PMID:15654517)
• regulation of the PLC pathway through the PTH1R is increased by elevating expression of G(11)alpha in osteoblastic cells leading to increased PTH stimulation of MMP-13 expression by increased stimulation of AP-1 factors c-jun and c-fos. (PMID:15693018)
• study showed a marked expression of MMP-13 in dental pulp tissue of both sound and carious teeth (PMID:15763932)
• MMP-9 and MMP-13 are involved in stroke progression and the neuroinflammatory response (PMID:15947272)
• Down-regulated by integrin alphavbeta6, not essential for the degradation of type I collagen by oral squamous cell carcinoma cells. (PMID:16024014)
• GADD45beta plays an essential role during chondrocyte terminal differentiation and mediates MMP-13 gene expression (PMID:16144844)
• activation of MMP-13 as well as MMP-9 induced by H-Ras is involved in angiogenesis and with farnesyl transferase inhibitors, in part, exerts their anticancer effects (PMID:16331612)
• MMP-13 appears to be a factor associated with tumor aggressiveness in cutaneous malignant melanoma (PMID:16398406)
• MMP-13 can degrade members from two classes of small leucine-rich repeat proteoglycans. Site at which biglycan is cleaved by MMP-13. MMP-13 induced SLRP degradation may represent early event affecting collagen network by exposing MMP-13 cleavage site. (PMID:16507124)
• the involvement of p38 MAP kinase in the hyaluronan oligosaccharide induction of MMP-13 (PMID:16648633)
• The expression of matrix-modeling genes in chronic idiopathic myelofibrosis (cIMF) is not influenced by the JAK2 mutation status but is predominantly related to the stage of disease. (PMID:16877349)
• a novel role for human MMP-13 in regulating dermal fibroblast survival, proliferation, and interaction in 3D collagen. (PMID:16917496)
• Since both S100A4 and RAGE are up-regulated in osteoarthritis cartilage, this signaling pathway could contribute to cartilage degradation in this disease. (PMID:16948116)
• TUNEL-positive cells and MMP-3- and -13-expressing cells were distributed in the degenerative articular cartilage and reparative fibrocartilage tissue in osteochondritis dissecans (OCD) of the elbow. (PMID:16984617)
• Premature induction of hypertrophy-related molecules (type X collagen and matrix metalloproteinase 13) occurred before production of type II collagen and was followed by up-regulation of alkaline phosphatase activity. (PMID:17009260)
• No convincing evidence was found to support the association of MMP13 SNPs with increased breast cancer risk or survival. (PMID:17033924)
• activity in gingival crevicular fluid samples was significantly increased in active sites from progressive periodontal disease, supporting its role in the alveolar bone loss (PMID:17076612)
• These results identify an unexpectedly broad involvement for p8 in key cellular events linked to cardiomyocyte hypertrophy and cardiac fibroblast matrix metalloproteases production, both of which occur in heart failure. (PMID:17116693)
• Thus, in the region of Hebei Province where there is a high incidence of GCA and ESCC, the MMP-13 A-77G SNP may not be associated with cancer susceptibility. (PMID:17138534)
• nicotine stimulates bone matrix turnover by increasing production of tPA and MMP-1, 2, 3, and 13, thereby tipping the balance between bone matrix formation and resorption toward the latter process (PMID:17151781)
• We have solved the 2.0 A crystal structure of the complex between the catalytic domain of human MMP-13 (cdMMP-13) and bovine TIMP-2. (PMID:17196980)
• oncostatin M-stimulated ADAMTS-4 and MMP-13 expression is mediated by extracellular signal-regulated kinases, Janus kinase 3/STAT1/3 and phosphatidylinositol 3-kinase/Akt and by cross talk between these pathways (PMID:17208315)
• deregulation of cross-talk between mitogen-activated protein kinases and protein kinase Cdelta signaling may contribute to the etiology of osteoarthritis in human patients (PMID:17311929)
• CpG-ODN-treatment also increased MMP-13 activity and neutralizing anti-MMP-13 antibody prevented CpG-ODN-induced invasion in TLR9(+) CaP cells. (PMID:17373717)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp30	ENSDARG00000045887
mus_musculus	Mmp13	ENSMUSG00000050578
rattus_norvegicus	Mmp13	ENSRNOG00000008478
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), 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

Collagenase 3 — P45452 (reviewed: P45452)

Alternative names: Matrix metalloproteinase-13

All UniProt accessions (2): P45452, G5E971

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.

Subunit / interactions. Monomer. Interacts with TIMP1, TIMP2 and TIMP3. Binds (via the C-terminal region) to collagen.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in fetal cartilage and calvaria, in chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. Detected in chondrocytes from in joint cartilage that have been treated with TNF and IL1B, but not in untreated chondrocytes. Detected in T lymphocytes. Detected in breast carcinoma tissue.

Post-translational modifications. The proenzyme is activated by removal of the propeptide; this cleavage can be effected by other matrix metalloproteinases, such as MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage can also be autocatalytic, after partial maturation by another protease or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro). N-glycosylated. Tyrosine phosphorylated by PKDCC/VLK.

Disease relevance. Spondyloepimetaphyseal dysplasia, Missouri type (SEMDM) [MIM:602111] A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age. The disease is caused by variants affecting the gene represented in this entry. Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111] A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia. The disease is caused by variants affecting the gene represented in this entry. Metaphyseal dysplasia, Spahr type (MDST) [MIM:250400] An autosomal recessive, rare disease characterized by moderate short stature, mild genua vara, and radiographic signs of metaphyseal dysplasia, but no biochemical signs of rickets. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by acetohydroxamic acid and other zinc chelators.

Cofactor. Can bind about 5 Ca(2+) ions per subunit. Binds 2 Zn(2+) ions per subunit.

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

Induction. Up-regulated by TNF and IL1B.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_002418* (*=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
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

Enzyme classification (BRENDA):

• EC 3.4.24.17 — stromelysin 1 (BRENDA: 6 organisms, 110 substrates, 260 inhibitors, 9 Km, 9 kcat entries)
• EC 3.4.24.35 — gelatinase B (BRENDA: 11 organisms, 258 substrates, 185 inhibitors, 17 Km, 18 kcat entries)
• EC 3.4.24.65 — macrophage elastase (BRENDA: 4 organisms, 95 substrates, 46 inhibitors, 48 Km, 48 kcat entries)
• EC 3.4.24.B4 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
FELN-100	0.001–0.0047	16
MCA-PRO-LEU-GLY-LEU-DPA-ALA-ARG-NH2	0.113–0.241	16
ARG-PRO-LYS-PRO-GLN-GLN-PHE-PHE-GLY-LEU-NORLEUCI	0.9–1.4	2
N-3-(2,4-DINITROPHENYL)-L-2,3-DIAMINOPROPIONYL-7	0.0042–0.005	2
STROMELYSIN1	—	2
2-AMINOBENZOYL-PLALWRSQ-2-(2,4-DINITROPHENYL)AMI	0.0202–0.0249	2
2-AMINOBENZOYL-PLGLEEA-2-(2,4-DINITROPHENYL)AMIN	0.0047–0.0091	2
2-AMINOBENZOYL-RPLALEESQ-2-(2,4-DINITROPHENYL)AM	0.0075–0.029	2
2-AMINOBENZOYL-RPLALWEEQ-2-(2,4-DINITROPHENYL)AM	0.0123–0.0146	2
2-AMINOBENZOYL-RPLALWESQ-2-(2,4-DINITROPHENYL)AM	0.0068–0.0138	2
2-AMINOBENZOYL-RPLALWRSQ-2-(2,4-DINITROPHENYL)AM	0.0144–0.0156	2
2-AMINOBENZOYL-RPLELWRSQ-2-(2,4-DINITROPHENYL)AM	0.0088–0.0093	2
2-AMINOBENZOYL-RPLGLEEA-2-(2,4-DINITROPHENYL)AMI	0.0103–0.0197	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-T	0.066	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-V	0.025	1

UniProt features (105 total): strand 33, binding site 30, helix 10, sequence variant 7, turn 4, repeat 4, sequence conflict 3, region of interest 3, glycosylation site 2, signal peptide 1, propeptide 1, short sequence motif 1, compositionally biased region 1, active site 1, chain 1, modified residue 1, disulfide bond 1, mutagenesis site 1

Structure

Experimental structures (PDB)

49 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5B5O	X-RAY DIFFRACTION	1.2
3ZXH	X-RAY DIFFRACTION	1.3
4JP4	X-RAY DIFFRACTION	1.43
3WV3	X-RAY DIFFRACTION	1.6
5B5P	X-RAY DIFFRACTION	1.6
5UWK	X-RAY DIFFRACTION	1.6
830C	X-RAY DIFFRACTION	1.6
5UWM	X-RAY DIFFRACTION	1.62
4L19	X-RAY DIFFRACTION	1.66
1XUC	X-RAY DIFFRACTION	1.7
2YIG	X-RAY DIFFRACTION	1.7
6HV2	X-RAY DIFFRACTION	1.71
2OW9	X-RAY DIFFRACTION	1.74
5BPA	X-RAY DIFFRACTION	1.79
1XUD	X-RAY DIFFRACTION	1.8
1XUR	X-RAY DIFFRACTION	1.85
5BOT	X-RAY DIFFRACTION	1.85
3ELM	X-RAY DIFFRACTION	1.9
3KRY	X-RAY DIFFRACTION	1.9
3O2X	X-RAY DIFFRACTION	1.9
3I7G	X-RAY DIFFRACTION	1.95
3KEK	X-RAY DIFFRACTION	1.97
3WV1	X-RAY DIFFRACTION	1.98
1ZTQ	X-RAY DIFFRACTION	2
2E2D	X-RAY DIFFRACTION	2
3LJZ	X-RAY DIFFRACTION	2
4JPA	X-RAY DIFFRACTION	2
7JU8	X-RAY DIFFRACTION	2
5BOY	X-RAY DIFFRACTION	2.03
3KEC	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P45452-F1	89.00	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): 223

Ligand- & substrate-binding residues (30): 96 (in inhibited form); 128; 162; 172; 174; 179; 180; 182; 184; 187; 194; 196 …

Post-translational modifications (1): 366

Disulfide bonds (1): 284–471

Glycosylation sites (2): 117, 152

Mutagenesis-validated functional residues (1):

Position	Phenotype
223	abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 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-8941332	RUNX2 regulates genes involved in cell migration
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878166	Transcriptional regulation by RUNX2

MSigDB gene sets: 327 (showing top): MODULE_172, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, FREAC2_01, CHIBA_RESPONSE_TO_TSA_UP, HARRIS_HYPOXIA, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, chr11q22, GOBP_GROWTH, GOBP_BONE_GROWTH, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_REPLACEMENT_OSSIFICATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT

GO Biological Process (9): endochondral ossification (GO:0001958), growth plate cartilage development (GO:0003417), proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), bone mineralization (GO:0030282), collagen catabolic process (GO:0030574), bone morphogenesis (GO:0060349), response to amyloid-beta (GO:1904645)

GO Molecular Function (10): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), collagen binding (GO:0005518), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	2
Collagen formation	1
Transcriptional regulation by RUNX2	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidase activity	2
endopeptidase activity	2
replacement ossification	1
endochondral bone morphogenesis	1
endochondral bone growth	1
cartilage development involved in endochondral bone morphogenesis	1
connective tissue development	1
protein metabolic process	1
cellular component disassembly	1
extracellular matrix organization	1
extracellular structure organization	1
external encapsulating structure organization	1
ossification	1
biomineral tissue development	1
catabolic process	1
collagen metabolic process	1
animal organ morphogenesis	1
skeletal system morphogenesis	1
bone development	1
response to nitrogen compound	1
response to oxygen-containing compound	1
metallopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
protein-containing complex binding	1
transition metal ion 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

Protein interactions and networks

STRING

2442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP13	ACAN	P16112	909
MMP13	COL10A1	Q03692	903
MMP13	ADAMTS3	O15072	901
MMP13	ADAMTS4	O75173	900
MMP13	ADAMTS5	Q9UNA0	897
MMP13	TIMP1	P01033	864
MMP13	COL2A1	P02458	856
MMP13	TIMP2	P16035	821
MMP13	IL1B	P01584	808
MMP13	RUNX2	Q13950	775
MMP13	SOX9	P48436	774
MMP13	IL6	P05231	744
MMP13	FN1	P02751	743
MMP13	TNFSF11	O14788	727
MMP13	CXCL8	P10145	726

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MMP13	HTRA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): MMP13 (Biochemical Activity), BCAN (Biochemical Activity), FBXO45 (Affinity Capture-MS), GID4 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), HTRA2 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), CS (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), ADAMTS2 (Affinity Capture-MS), MAEA (Affinity Capture-MS), ARMC8 (Affinity Capture-MS)

ESM2 similar proteins: O13065, O18767, O18927, O35548, O55123, O60882, O62806, O70138, O77656, O88766, P03956, P03957, P07152, P08253, P08254, P09238, P13943, P21692, P22894, P23097, P28053, P28862, P28863, P33434, P33435, P33436, P34960, P39900, P45452, P50281, P53690, P57748, P79227, P79287, Q10739, Q10835, Q11005, Q28397, Q5RES1, Q63341

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

23 interactions.

A	Effect	B	Mechanism
CITED2	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
ETS1	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
PTH	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
HDAC4	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
ING2	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
JUN	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
MAF	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
NfKb-p65/p50	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
BMP7	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
IGF1	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
RUNX2	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
FGF2	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”
SPDEF	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
STAT1	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
YBX1	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
MMP13	“down-regulates quantity by destabilization”	COL2A1	cleavage
MMP13	“down-regulates quantity by destabilization”	F12	cleavage
MMP13	“down-regulates quantity by destabilization”	FGA	cleavage
MMP13	“down-regulates quantity by destabilization”	FGG	cleavage
MMP13	“down-regulates quantity by destabilization”	FGB	cleavage
MMP13	up-regulates	ECM_disassembly
MMP13	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	8
Uncertain significance	150
Likely benign	73
Benign	30

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1037126	NM_002427.4(MMP13):c.539G>C (p.Gly180Ala)	Pathogenic
1383389	NM_002427.4(MMP13):c.974C>A (p.Ser325Ter)	Pathogenic
2035434	NM_002427.4(MMP13):c.1166_1175dup (p.Lys393fs)	Pathogenic
2066110	NM_002427.4(MMP13):c.1080T>G (p.Tyr360Ter)	Pathogenic
2807360	NM_002427.4(MMP13):c.779_786del (p.Gln260fs)	Pathogenic
3701195	NM_002427.4(MMP13):c.1108del (p.Ile370fs)	Pathogenic
4727306	NM_002427.4(MMP13):c.544del (p.Ser182fs)	Pathogenic
9443	NM_002427.4(MMP13):c.224T>C (p.Phe75Ser)	Pathogenic
9446	NM_002427.4(MMP13):c.694C>A (p.His232Asn)	Pathogenic
1066000	NM_002427.4(MMP13):c.511+2T>A	Likely pathogenic
1067180	NM_002427.4(MMP13):c.1052-1G>C	Likely pathogenic
1470817	NM_002427.4(MMP13):c.1212-1G>T	Likely pathogenic
2097868	NM_002427.4(MMP13):c.512-1G>C	Likely pathogenic
2981810	NM_002427.4(MMP13):c.800-1G>T	Likely pathogenic
373391	NM_002427.4(MMP13):c.1052-2A>C	Likely pathogenic
4081515	NM_002427.4(MMP13):c.1208G>A (p.Trp403Ter)	Likely pathogenic
853177	NM_002427.4(MMP13):c.800-1G>A	Likely pathogenic

SpliceAI

965 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102944363:TAAC:T	acceptor_gain	1.0000
11:102944367:C:CA	acceptor_loss	1.0000
11:102944367:C:CC	acceptor_gain	1.0000
11:102944368:T:C	acceptor_loss	1.0000
11:102945642:TTACC:T	donor_loss	1.0000
11:102945644:A:AC	donor_gain	1.0000
11:102945644:AC:A	donor_gain	1.0000
11:102945644:ACC:A	donor_loss	1.0000
11:102945645:C:CT	donor_gain	1.0000
11:102945645:CC:C	donor_gain	1.0000
11:102945645:CCA:C	donor_gain	1.0000
11:102945645:CCAT:C	donor_gain	1.0000
11:102945645:CCATT:C	donor_gain	1.0000
11:102945745:CATAT:C	acceptor_gain	1.0000
11:102945746:ATAT:A	acceptor_gain	1.0000
11:102945747:TAT:T	acceptor_gain	1.0000
11:102945748:AT:A	acceptor_gain	1.0000
11:102945749:TC:T	acceptor_loss	1.0000
11:102945750:C:CC	acceptor_gain	1.0000
11:102945752:A:C	acceptor_gain	1.0000
11:102945753:T:TC	acceptor_gain	1.0000
11:102945754:T:C	acceptor_gain	1.0000
11:102945754:T:TC	acceptor_gain	1.0000
11:102947878:A:AC	donor_gain	1.0000
11:102947879:C:CC	donor_gain	1.0000
11:102949019:GCTTA:G	donor_loss	1.0000
11:102949020:CTTA:C	donor_loss	1.0000
11:102949021:TTACC:T	donor_loss	1.0000
11:102949022:TACCT:T	donor_loss	1.0000
11:102949023:A:AC	donor_gain	1.0000

AlphaMissense

3152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102949070:C:G	A336P	0.999
11:102950153:C:G	A292P	0.999
11:102952039:C:G	D258H	0.999
11:102952091:C:A	M240I	0.999
11:102952091:C:G	M240I	0.999
11:102952091:C:T	M240I	0.999
11:102952092:A:G	M240T	0.999
11:102952099:C:G	A238P	0.999
11:102952113:G:A	S233F	0.999
11:102952115:G:C	H232Q	0.999
11:102952115:G:T	H232Q	0.999
11:102952122:A:G	L230P	0.999
11:102952133:G:C	H226Q	0.999
11:102952133:G:T	H226Q	0.999
11:102952135:G:C	H226D	0.999
11:102952137:C:T	G225D	0.999
11:102952142:C:A	E223D	0.999
11:102952142:C:G	E223D	0.999
11:102952147:G:C	H222D	0.999
11:102954172:C:A	W207C	0.999
11:102954172:C:G	W207C	0.999
11:102954174:A:G	W207R	0.999
11:102954174:A:T	W207R	0.999
11:102954191:A:G	F201S	0.999
11:102954259:A:C	F178L	0.999
11:102954259:A:T	F178L	0.999
11:102954261:A:G	F178L	0.999
11:102954468:A:C	F167L	0.999
11:102954468:A:T	F167L	0.999
11:102954470:A:G	F167L	0.999

dbSNP variants (sampled 300 via entrez): RS1000106881 (11:102944658 G>A), RS1000171358 (11:102942766 G>A), RS1000439859 (11:102950601 T>G), RS1000457260 (11:102957701 G>A,T), RS1000556506 (11:102954405 G>A,T), RS1000624879 (11:102952506 A>G), RS1000928494 (11:102953863 G>A), RS1001711117 (11:102951877 T>A,C), RS1001838217 (11:102947744 G>A,T), RS1002197047 (11:102955797 G>C), RS1002553658 (11:102957631 TATTA>T), RS1002931211 (11:102957299 T>C), RS1003795699 (11:102948911 G>A,C), RS1003847890 (11:102950524 A>C), RS1004028258 (11:102957440 T>C)

Disease associations

OMIM: gene MIM:600108 | disease phenotypes: MIM:250400, MIM:602111, MIM:309645

GenCC curated gene-disease

Disease	Classification	Inheritance
metaphyseal chondrodysplasia, Spahr type	Definitive	Autosomal recessive
spondyloepimetaphyseal dysplasia, Missouri type	Definitive	Autosomal dominant
metaphyseal anadysplasia	Supportive	Autosomal dominant

Mondo (4): intellectual disability (MONDO:0001071), metaphyseal chondrodysplasia, Spahr type (MONDO:0009597), spondyloepimetaphyseal dysplasia, Missouri type (MONDO:0011198), metaphyseal anadysplasia (MONDO:0015177)

Orphanet (4): Metaphyseal anadysplasia (Orphanet:1040), Metaphyseal chondrodysplasia, Spahr type (Orphanet:2501), Spondyloepimetaphyseal dysplasia, Missouri type (Orphanet:93356), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000670	Carious teeth
HP:0000926	Platyspondyly
HP:0000944	Abnormal metaphysis morphology
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001377	Limited elbow extension
HP:0001385	Hip dysplasia
HP:0001387	Joint stiffness
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002651	Spondyloepimetaphyseal dysplasia
HP:0002750	Delayed skeletal maturation
HP:0002758	Osteoarthritis
HP:0002812	Coxa vara
HP:0002814	Abnormality of the lower limb
HP:0002857	Genu valgum
HP:0002869	Flared iliac wing
HP:0002970	Genu varum
HP:0002979	Bowing of the legs
HP:0002980	Femoral bowing
HP:0002982	Tibial bowing
HP:0002986	Radial bowing
HP:0003015	Flared metaphysis
HP:0003016	Metaphyseal widening
HP:0003021	Metaphyseal cupping
HP:0003025	Metaphyseal irregularity
HP:0003031	Ulnar bowing

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002665_4	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2.000000e-44
GCST002875_148	Diisocyanate-induced asthma	1.000000e-09
GCST006039_3	Peanut allergy	3.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004744	matrix metalloproteinase measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0006995	response to diisocyanate
EFO:0007017	peanut allergy measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C537351	Metaphyseal anadysplasia (supp.)
C537353	Metaphyseal chondrodysplasia Spahr type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095216 (PROTEIN FAMILY), CHEMBL2111422 (SELECTIVITY GROUP), CHEMBL280 (SINGLE PROTEIN), CHEMBL4523970 (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: 362,385 (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
CHEMBL1200699	DOXYCYCLINE	4	93,821
CHEMBL140	CURCUMIN	3	93,882
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL50	QUERCETIN	3	74,559
CHEMBL75094	PRINOMASTAT	3	8,839
CHEMBL115653	CIPEMASTAT	2	359
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL206815	APRATASTAT	2	256
CHEMBL261932	TANOMASTAT	2	1,980
CHEMBL279786	BATIMASTAT	2	21,247
CHEMBL440498	CTS-1027	2	615

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs640198	MMP13		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
prinomastat	Inhibition	10.4	pIC50
ilomastat	Inhibition	9.55	pIC50
SL422	Inhibition	9.35	pKi
compound 1 [PMID: 17935984]	Inhibition	9.2	pIC50
compound 15 [PMID: 22017539]	Inhibition	9.0	pIC50
PF-152	Inhibition	8.82	pIC50
marimastat	Inhibition	8.7	pIC50
batimastat	Inhibition	8.3	pIC50
AZD6605	Inhibition	8.3	pIC50
apratastat	Inhibition	8.1	pIC50
MMP13 tracer [18F]5j	Inhibition	7.8	pIC50
[18F]FMBP	Inhibition	7.25	pIC50
TP0556351	Inhibition	6.76	pIC50

Binding affinities (BindingDB)

418 measured of 641 human assays (641 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-hydroxy-1-(2-methoxyethyl)-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide hydrochloride	KI	0.1 nM
1-Cyclopropyl-N-hydroxy-4-{[4-(phenylthio)phenyl]-sulfonyl}piperidine-4-carboxamide Hydrochloride	KI	0.1 nM
N-hydroxy-2-methyl-2-[(4-phenoxybenzene)sulfonyl]propanamide	KI	0.1 nM
N-Hydroxy-4-{[4-(phenoxyphenyl]sulfonyl}-1- (2-propynyl)4-piperidinecarboxamide, Monohydrochloride	KI	0.13 nM
N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}-1-(prop-2-en-1-yl)piperidine-4-carboxamide hydrochloride	KI	0.15 nM
piperidinyl glycine derivative, 24f	KI	0.19 nM
tert-Butyl 4-[(Hydroxyamino)carbonyl]-4-{[(4-phenoxyphenyl)sulfonyl]methyl}piperidine-1-carboxylate	KI	0.2 nM
N-hydroxy-1-[(3-methoxyphenyl)methyl]-4-{[(4-phenoxybenzene)sulfonyl]methyl}piperidine-4-carboxamide hydrochloride	KI	0.2 nM
tert-butyl 4-(hydroxycarbamoyl)-4-[(4-phenoxybenzene)sulfonyl]piperidine-1-carboxylate	KI	0.2 nM
1-cyclopropyl-N-hydroxy-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide hydrochloride	KI	0.2 nM
N-hydroxy-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide	KI	0.22 nM
N-hydroxy-4-{[(4-phenoxybenzene)sulfonyl]methyl}-1-(prop-2-yn-1-yl)piperidine-4-carboxamide hydrochloride	KI	0.25 nM
N-Hydroxy-4-{[(4-phenoxyphenyl)sulfonyl]methyl}-1-(2-phenylethyl)piperidine-4-carboxamide Hydrochloride	KI	0.3 nM
N-hydroxy-1-methanesulfonyl-4-[(4-phenoxybenzene)sulfonyl]piperidine-4-carboxamide	KI	0.3 nM
N-hydroxy-1-(2-methoxyethyl)-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide hydrochloride	KI	0.3 nM
BOC-piperidinyl glycine derivative, 9	IC50	0.3 nM
BOC-piperidinyl glycine derivative, 31	IC50	0.3 nM
N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}-1-(prop-2-yn-1-yl)piperidine-4-carboxamide hydrochloride	KI	0.33 nM
(3R)-N-hydroxy-2-{[4-(4-methoxyphenyl)phenyl]methyl}-1,1-dioxo-1,2-thiazinane-3-carboxamide	KI	0.4 nM
alpha-tetrahydropyran beta-sulfone 1B	KI	0.4 nM
1-acetyl-N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide	KI	0.4 nM
piperidinyl glycine derivative, 24q	IC50	0.4 nM
piperidinyl glycine derivative, 24u	IC50	0.4 nM
N-Hydroxy-1-methyl-4-{[4-(phenylthio)phenyl]sulfonyl}-piperidine-4-carboxamide Hydrochloride	KI	0.5 nM
BOC-piperidinyl glycine derivative, 34	IC50	0.5 nM
BOC-piperidinyl glycine derivative, 35	IC50	0.5 nM
piperidinyl glycine derivative, 24t	IC50	0.5 nM
Trocade	KI	0.53 nM
piperidinyl glycine derivative, 24d	IC50	0.6 nM
piperidinyl glycine derivative, 24p	IC50	0.6 nM
piperidinyl glycine derivative, 24s	IC50	0.6 nM
N,N -bis(4-fluoro-3-methylbenzyl)pyrimidine-4,6-dicarboxamide	IC50	0.67 nM
4-{[1-METHYL-2,4-DIOXO-6-(3-PHENYLPROP-1-YN-1-YL)-1,4-DIHYDROQUINAZOLIN-3(2H)-YL]METHYL}BENZOIC ACID	IC50	0.67 nM
BOC-piperidinyl glycine derivative, 32	IC50	0.7 nM
piperidinyl glycine derivative, 27c	IC50	0.7 nM
piperidinyl glycine derivative, 27d	IC50	0.7 nM
BOC-piperidinyl glycine derivative, 22a	IC50	0.75 nM
1-ethyl-N-hydroxy-4-{[4-(phenylsulfanyl)benzene]sulfonyl}piperidine-4-carboxamide hydrochloride	KI	0.8 nM
piperidinyl glycine derivative, 24g	IC50	0.8 nM
piperidinyl glycine derivative, 24o	IC50	0.8 nM
piperidinyl glycine derivative, 25c	IC50	0.8 nM
4-({[4-(3,4-Dimethylphenoxy)phenyl]sulfonyl}methyl)-N-hydroxy-1-prop-2-ynylpiperidine-4-carboxamide Hydrochloride	KI	0.9 nM
piperidinyl glycine derivative, 24i	IC50	0.9 nM
piperidinyl glycine derivative, 24r	IC50	0.9 nM
piperidinyl glycine derivative, 26d	IC50	0.9 nM
(3R)-N-hydroxy-1,1-dioxo-2-{[4-(pyridin-4-yl)phenyl]methyl}-1,2-thiazinane-3-carboxamide	KI	1 nM
piperidinyl glycine derivative, 24n	IC50	1 nM
(R)-N4-Hydroxy-N1-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide	IC50	1 nM	US-9487462: Inhibitors of matrix metalloproteinases
(2S)-3-methyl-2-{[12-({[2-(thiophen-2-yl)ethyl]carbamoyl}amino)-8-oxatricyclo[7.4.0.0^{2,7}]trideca-1(9),2(7),3,5,10,12-hexaene-5-]sulfonamido}butanoic acid	IC50	1.1 nM
piperidinyl glycine derivative, 27b	IC50	1.2 nM

ChEMBL bioactivities

3311 potent at pChembl≥5 of 3511 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CTS-1027
10.82	IC50	0.015	nM	CHEMBL3337892
10.80	IC50	0.016	nM	CHEMBL317132
10.74	IC50	0.018	nM	CHEMBL3337891
10.74	IC50	0.018	nM	CHEMBL3337898
10.70	IC50	0.02	nM	CHEMBL2064548
10.68	IC50	0.021	nM	CHEMBL3337903
10.62	IC50	0.024	nM	CHEMBL4087855
10.59	IC50	0.026	nM	CHEMBL3337900
10.59	IC50	0.026	nM	CHEMBL4094620
10.57	IC50	0.027	nM	CHEMBL4079123
10.55	IC50	0.028	nM	CHEMBL3337896
10.54	IC50	0.029	nM	CHEMBL3337893
10.52	IC50	0.03	nM	CHEMBL2047536
10.52	IC50	0.03	nM	CHEMBL3359090
10.52	IC50	0.03	nM	CHEMBL473539
10.52	Ki	0.03	nM	PRINOMASTAT
10.49	IC50	0.032	nM	CHEMBL3337889
10.48	IC50	0.033	nM	CHEMBL4092215
10.47	IC50	0.034	nM	CHEMBL4059519
10.44	IC50	0.036	nM	CHEMBL4068176
10.42	Ki	0.038	nM	PRINOMASTAT
10.40	IC50	0.04	nM	CHEMBL2064549
10.40	IC50	0.04	nM	CHEMBL2425941
10.40	IC50	0.04	nM	CHEMBL2425949
10.40	IC50	0.04	nM	CHEMBL3359088
10.37	IC50	0.043	nM	CHEMBL4103367
10.30	IC50	0.05	nM	CHEMBL2425947
10.30	IC50	0.05	nM	CHEMBL250776
10.30	IC50	0.05	nM	CHEMBL1914483
10.29	IC50	0.051	nM	CHEMBL3889936
10.28	IC50	0.053	nM	CHEMBL3337902
10.28	IC50	0.052	nM	CHEMBL3958969
10.27	IC50	0.054	nM	CHEMBL4090287
10.24	IC50	0.057	nM	CHEMBL4069240
10.23	IC50	0.059	nM	CHEMBL4078492
10.21	IC50	0.062	nM	CHEMBL330028
10.21	IC50	0.062	nM	CHEMBL4086342
10.19	IC50	0.064	nM	CHEMBL4068241
10.15	IC50	0.07	nM	CHEMBL2425938
10.15	IC50	0.07	nM	CHEMBL2425936
10.15	IC50	0.071	nM	CHEMBL3978380
10.15	IC50	0.07	nM	CHEMBL4584968
10.13	IC50	0.074	nM	CHEMBL4064516
10.11	IC50	0.078	nM	CHEMBL3965628
10.10	IC50	0.08	nM	CHEMBL3337890
10.10	IC50	0.08	nM	CHEMBL250758
10.05	IC50	0.09	nM	CHEMBL2064542
10.05	IC50	0.09	nM	CHEMBL2425950
10.05	IC50	0.09	nM	CHEMBL250570

PubChem BioAssay actives

3363 with measured affinity, of 4457 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-[[2-[(3-methoxyphenyl)methylcarbamoyl]-4-oxo-3H-thieno[2,3-d]pyrimidin-5-yl]methoxymethyl]benzoic acid	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
(1S)-4-methyl-1-[[5-[(3-oxo-4H-1,4-benzoxazin-6-yl)methylcarbamoyl]pyrazolo[1,5-a]pyrimidine-7-carbonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid	1929089: Inhibition of MMP-13 (unknown origin)	ic50	<0.0001	uM
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[[(2R)-2-[[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]methyl]-4-(hydroxyamino)-4-oxobutanoyl]amino]butanoyl]amino]-5-oxopentanoic acid	1460165: Inhibition of human MMP13 catalytic domain using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 fluorogenic substrate by spectrophotometric analysis	ki	<0.0001	uM
4-[2-[[6-fluoro-2-[(3-methoxyphenyl)methylcarbamoyl]-4-oxo-3H-quinazolin-5-yl]oxy]ethyl]benzoic acid	1166661: Inhibition of human recombinant MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate after 40 mins by spectrofluorimetry	ic50	<0.0001	uM
5-[2-(4-aminophenyl)ethoxy]-6-fluoro-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-quinazoline-2-carboxamide	1166661: Inhibition of human recombinant MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate after 40 mins by spectrofluorimetry	ic50	<0.0001	uM
6-fluoro-N-[(3-methoxyphenyl)methyl]-4-oxo-5-(2-phenylethoxy)-3H-quinazoline-2-carboxamide	1166661: Inhibition of human recombinant MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate after 40 mins by spectrofluorimetry	ic50	<0.0001	uM
N-[[3-[4-[[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]phenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328774: Inhibition of recombinant human AMPA-activated MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
4-oxo-5-phenyl-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
5-(2-fluorophenyl)-4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
5-(3-fluorophenyl)-4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1166661: Inhibition of human recombinant MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate after 40 mins by spectrofluorimetry	ic50	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-phenoxyphenyl)sulfonylthiomorpholine-3-carboxamide	1863881: Inhibition of MMP-13 (unknown origin)	ic50	<0.0001	uM
(3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide	109387: Inhibition of collagenase (Matrix metalloprotease-13)	ki	<0.0001	uM
(2R)-2-[[1-(2-fluoroethyl)triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	675791: Inhibition of MMP13 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	<0.0001	uM
2-[2-[2-[2-[4-[[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate	675791: Inhibition of MMP13 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	<0.0001	uM
(2R)-2-[[1-[2-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]ethyl]triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	675791: Inhibition of MMP13 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl)Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured for 10 mins by fluorometry	ic50	<0.0001	uM
4-oxo-5-thiophen-2-yl-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
5-(3-methoxyphenyl)-4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
4-oxo-5-thiophen-3-yl-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
5-methyl-4-oxo-N-[[3-[3-(1H-1,2,4-triazol-5-ylsulfanyl)propoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433726: Inhibition of APMA-activated recombinant human MMP-13 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	<0.0001	uM
5-[(4-carbamoylphenyl)methoxymethyl]-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
4-[[[2-[(3-methoxyphenyl)methylcarbamoyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-5-carbonyl]amino]methyl]benzoic acid	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
5-N-benzyl-2-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2,5-dicarboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
5-(benzamidomethyl)-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
5-(2-anilino-2-oxoethyl)-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
4-[[2-[2-[(3-methoxyphenyl)methylcarbamoyl]-4-oxo-3H-thieno[2,3-d]pyrimidin-5-yl]acetyl]amino]benzoic acid	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
N-[(3-methoxyphenyl)methyl]-5-[[4-(methylcarbamoyl)phenyl]methoxymethyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
4-[2-[[2-[(3-methoxyphenyl)methylcarbamoyl]-4-oxo-3H-thieno[2,3-d]pyrimidin-5-yl]amino]-2-oxoethyl]benzoic acid	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
5-[[4-(hydroxymethyl)phenyl]methoxymethyl]-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
4-[[2-[(3-methoxyphenyl)methylcarbamoyl]-4-oxo-3H-thieno[2,3-d]pyrimidin-5-yl]methylcarbamoyl]benzoic acid	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
5-[(4-cyanophenyl)methoxymethyl]-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1162780: Inhibition of human recombinant MMP13 catalytic domain using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	<0.0001	uM
(2R)-2-[2-[4-[4-[(2-fluoro-3-pyridinyl)oxy]butyl]triazol-1-yl]ethyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide	769891: Inhibition of MMP-13 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	<0.0001	uM
(2R)-2-[cyanomethyl-[4-(2-fluoroethoxy)phenyl]sulfonylamino]-N-hydroxy-3-methylbutanamide	769891: Inhibition of MMP-13 (unknown origin) using 7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay	ic50	<0.0001	uM
2-[[4-(4-chlorophenyl)phenoxy]methyl]-N-hydroxy-4-(4-oxo-1,2,3-benzotriazin-3-yl)butanamide	109264: Inhibition of Matrix metalloprotease-13	ic50	<0.0001	uM
2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid	732016: Inhibition of MMP13 (unknown origin)	ic50	<0.0001	uM
N-hydroxy-2-[(4-phenoxyphenyl)sulfonylmethyl]-1-prop-2-ynylpyrrolidine-2-carboxamide	109377: Inhibitory activity against human Matrix metalloprotease-13	ic50	0.0001	uM
1-[6-[4-[4-(3-fluorophenyl)-1,3-oxazol-2-yl]phenoxy]-3-pyridinyl]-1,7,9-triazaspiro[4.5]decane-6,8,10-trione	310331: Inhibition of MMP13	ic50	0.0001	uM
N-hydroxy-1-(pyridin-2-ylmethyl)-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide	604454: Inhibition of human MMP13 assessed as cleavage of fluorogenic peptide MCAPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by fluorometric assay	ic50	0.0001	uM
4-[[6-[3-(4-methoxyphenyl)prop-1-ynyl]-4-oxoquinazolin-3-yl]methyl]benzoic acid	317511: Inhibition of human MMP13 catalytic domain	ic50	0.0001	uM
4-[2-[4-[[5-(6,8,10-trioxo-1,7,9-triazaspiro[4.5]decan-1-yl)-2-pyridinyl]oxy]phenyl]-1,3-oxazol-4-yl]benzonitrile	310331: Inhibition of MMP13	ic50	0.0001	uM
(2R,3S)-N-[(2S)-3-[4-(diaminomethylideneamino)phenyl]-1-(methylamino)-1-oxopropan-2-yl]-N’-hydroxy-2-(2-methylpropyl)-3-(3-phenylpropyl)butanediamide	347022: Inhibition of MMP13	ic50	0.0001	uM
(2R,4Z)-1-(4-butoxyphenyl)sulfonyl-N-hydroxy-4-(2-methylpropoxyimino)pyrrolidine-2-carboxamide	109256: In vitro inhibition of human recombinant collagenase-3 (Matrix metalloprotease-13)	ic50	0.0001	uM
(2R,4Z)-1-(4-butoxyphenyl)sulfonyl-N-hydroxy-4-phenylmethoxyiminopyrrolidine-2-carboxamide	109256: In vitro inhibition of human recombinant collagenase-3 (Matrix metalloprotease-13)	ic50	0.0001	uM
1-(cyclopropylmethyl)-N-hydroxy-4-(4-phenoxyphenyl)sulfonylpiperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0001	uM
N-hydroxy-1-(2-methoxyethyl)-4-(4-phenoxyphenyl)sulfonylpiperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0001	uM
N-hydroxy-1-methyl-4-(4-phenoxyphenyl)sulfonylpiperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0001	uM
1-acetyl-N-hydroxy-4-(4-phenoxyphenyl)sulfonylpiperidine-4-carboxamide	1796811: Enzyme Inhibition Assay from Article 10.1021/jm0500875: “Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.”	ki	0.0001	uM
3-[2-[4-[[5-(6,8,10-trioxo-1,7,9-triazaspiro[4.5]decan-1-yl)-2-pyridinyl]oxy]phenyl]-1,3-oxazol-4-yl]benzonitrile	310331: Inhibition of MMP13	ic50	0.0001	uM
5-(3-chlorophenyl)-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1328774: Inhibition of recombinant human AMPA-activated MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0001	uM
6-fluoro-5-[2-(4-fluorophenyl)ethoxy]-N-[(3-methoxyphenyl)methyl]-4-oxo-3H-quinazoline-2-carboxamide	1166661: Inhibition of human recombinant MMP13 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate after 40 mins by spectrofluorimetry	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Glucosamine	increases secretion, affects expression, decreases reaction, increases expression	5
Lipopolysaccharides	decreases expression, increases reaction, affects response to substance, decreases reaction, increases expression	5
sodium arsenite	decreases expression, increases expression	4
Resveratrol	decreases reaction, increases expression, increases secretion, decreases secretion	4
Particulate Matter	decreases reaction, increases expression, decreases expression	4
SB 203580	decreases reaction, increases expression	3
pyrazolanthrone	decreases reaction, increases expression	3
Arsenic Trioxide	decreases secretion, increases expression, decreases expression	3
T-2 Toxin	decreases reaction, increases expression, affects expression, affects response to substance	3
cobaltiprotoporphyrin	decreases reaction, increases expression, decreases expression	2
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	decreases reaction, increases expression	2
manganese(III)-tetrakis(4-benzoic acid)porphyrin	increases expression, increases secretion, decreases reaction, increases activity	2
dieckol	decreases reaction, increases expression, decreases expression	2
Decitabine	affects cotreatment, increases expression	2
Acetylcysteine	decreases reaction, increases expression, increases secretion, increases reaction	2
Benzene	increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Cadmium	decreases expression, increases abundance, increases expression	2
Calcitriol	decreases expression	2
Deoxyglucose	decreases expression, decreases reaction, increases expression	2
Doxycycline	decreases reaction, increases expression, decreases activity	2
Estradiol	affects cotreatment, increases expression	2
Nicotine	increases expression, affects reaction	2
Masoprocol	decreases reaction, increases expression, increases secretion	2
Oxygen	increases expression, increases reaction, decreases expression	2
Quercetin	increases reaction, decreases reaction, increases expression	2
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	2
Tetradecanoylphorbol Acetate	decreases reaction, increases expression	2
Simvastatin	decreases reaction, increases expression	2
sotorasib	affects cotreatment, decreases expression	1

ChEMBL screening assays

452 unique, capped per target: 435 binding, 8 admet, 6 functional, 3 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4481593	Binding	Inhibition of collagenase (unknown origin) at 200 uM relative to control	Deleting a Chromatin Remodeling Gene Increases the Diversity of Secondary Metabolites Produced by Colletotrichum higginsianum. — J Nat Prod
CHEMBL663111	Functional	In vitro antagonist activity against collagenase induced gel-filtered platelet (GFP) aggregation at 50 uM; NA=Inactive	Discovery and optimization of a novel series of thrombin receptor (par-1) antagonists: potent, selective peptide mimetics based on indole and indazole templates. — J Med Chem
CHEMBL1738688	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development efforts to identify inhibitors of Matrix Metalloprotease-13 (MMP-13). (Class of assay: screening) [Related pubchem assays (depositor defined):AID1931, AID570, AID734, AID735, A	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7YA	Abcam Raji MMP13 KO	Cancer cell line	Male
CVCL_B9Z0	Abcam THP-1 MMP13 KO	Cancer cell line	Male
CVCL_C7AQ	Abcam PC-3 MMP13 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders