ADAMTS5

Summary

ADAMTS5 (ADAM metallopeptidase with thrombospondin type 1 motif 5, HGNC:221) is a protein-coding gene on chromosome 21q21.3, encoding A disintegrin and metalloproteinase with thrombospondin motifs 5 (Q9UNA0). Metalloproteinase that plays an important role in connective tissue organization, development, inflammation and cell migration.

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and functions as an aggrecanase that cleaves aggrecan, a major proteoglycan of cartilage, and may mediate cartilage destruction in osteoarthritis.

Source: NCBI Gene 11096 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 162 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007038

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:221
Approved symbol	ADAMTS5
Name	ADAM metallopeptidase with thrombospondin type 1 motif 5
Location	21q21.3
Locus type	gene with protein product
Status	Approved
Aliases	ADMP-2, ADAMTS11
Ensembl gene	ENSG00000154736
Ensembl biotype	protein_coding
OMIM	605007
Entrez	11096

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000284987, ENST00000652031, ENST00000970346

RefSeq mRNA: 1 — MANE Select: NM_007038 NM_007038

CCDS: CCDS13579

Canonical transcript exons

ENST00000284987 — 8 exons

Exon	Start	End
ENSE00001017386	26943380	26943547
ENSE00001017387	26917922	26924620
ENSE00001017388	26932004	26932179
ENSE00001017389	26932861	26933044
ENSE00001017390	26954739	26954871
ENSE00001017391	26965288	26967088
ENSE00001017392	26934466	26934749
ENSE00001017393	26929886	26930061

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.6178 / max 767.5757, expressed in 1027 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190032	15.4741	958
190033	1.9054	510
190029	0.3763	187
190031	0.3316	157
190035	0.2040	94
190034	0.1397	76
190028	0.1170	34
190030	0.0698	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mammary duct	UBERON:0001765	97.98	gold quality
epithelium of mammary gland	UBERON:0003244	96.73	gold quality
synovial joint	UBERON:0002217	96.39	gold quality
stromal cell of endometrium	CL:0002255	96.01	gold quality
skin of hip	UBERON:0001554	95.44	gold quality
decidua	UBERON:0002450	95.31	gold quality
layer of synovial tissue	UBERON:0007616	94.57	gold quality
mammary gland	UBERON:0001911	92.69	gold quality
thoracic mammary gland	UBERON:0005200	92.62	gold quality
choroid plexus epithelium	UBERON:0003911	89.81	gold quality
endothelial cell	CL:0000115	89.45	gold quality
placenta	UBERON:0001987	89.24	gold quality
buccal mucosa cell	CL:0002336	88.72	gold quality
mucosa of stomach	UBERON:0001199	88.55	gold quality
parietal pleura	UBERON:0002400	88.53	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.90	gold quality
pleura	UBERON:0000977	86.88	gold quality
adipose tissue	UBERON:0001013	86.78	gold quality
mammalian vulva	UBERON:0000997	86.53	gold quality
connective tissue	UBERON:0002384	86.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.20	gold quality
visceral pleura	UBERON:0002401	85.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.87	gold quality
tibia	UBERON:0000979	83.99	gold quality
calcaneal tendon	UBERON:0003701	83.77	gold quality
cauda epididymis	UBERON:0004360	83.68	gold quality
upper leg skin	UBERON:0004262	83.44	gold quality
myometrium	UBERON:0001296	83.30	gold quality
superficial temporal artery	UBERON:0001614	82.45	gold quality
cartilage tissue	UBERON:0002418	82.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	4539.71
E-ANND-3	yes	25.43
E-MTAB-10290	no	91.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, HES1, NR2C2, RELA, SIRT1, TCF3

miRNA regulators (miRDB)

385 targeting ADAMTS5, 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-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979

Literature-anchored findings (GeneRIF, showing 40)

• Aggrecanase-2 mRNA and protein are constitutively produced by fibroblast-like synoviocytes from nonarthritis, osteoarthritis, and rheumatoid arthritis patients but are not increased by TGF-beta, IL-1, or TNF-alpha. (PMID:11801682)
• extracellular matrix degrading enzyme (PMID:11831030)
• Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage. (PMID:11956193)
• Substrate specificity. Cleaves aggrecan at Glu(1480)-Gly(1481), Glu(1667)-Gly(1668), Glu(1771)-Ala(1772) and Glu(1871)-Leu(1872) bonds more readily than at the Glu(373)-Ala(374) bond. Additionally, in region spanning residues Gly(1481) and Glu(1667). (PMID:12392761)
• ADAMTS4 and ADAMTS5 are inhibited by alpha2-macroglobulin (PMID:14715656)
• negative effect of TGFbeta1 on ADAMTS-1, -5, -9, and -15 coupled with increases in their inhibitor, TIMP-3 may aid the accumulation of versican in the stromal compartment of the prostate in BPH and prostate cancer (PMID:15599946)
• ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells, and these proteases may contribute to their invasive potential (PMID:16003758)
• These results demonstrate for the first time that ADAMTS-5 is capable of degrading brevican and is overexpressed in glioblastoma cells, and suggest that ADAMTS-5 may play a role in glioma cell invasion through the cleavage of brevican. (PMID:16133547)
• effects of C-terminal truncation on GAG-binding properties & aggrecanase activity of ADAMTS-5 bound to sulfated GAGs. Further truncation reduced aggrecanase activity, although appreciable GAG binding affinity was maintained. (PMID:16507336)
• ADAMTS-5 expression is restricted to decidualized stromal cells of the human endometrium in vivo and is subject to regulation by cytokines in vitro. (PMID:17067994)
• Analysis of ADAMTS-5 (aggrecanase-2) gene promoter sequence indicated four putative binding sites for the Runx family of transcription factors and suggested ADAMTS-5 to be a potential downstream target of Runx2. (PMID:17211519)
• Our data suggest that both ADAMTS-4 and ADAMTS-5 contribute to the structural damage that characterizes human osteoarthritis. (PMID:17265492)
• Chondrocytes with low chondrogenic capacity expressed higher levels of IGF-1, MMP-2, aggrecanase 2, while chondrocytes with high chondrogenic capacity expressed higher levels of CD44, CD151, and CD49c. (PMID:17265493)
• ADAMTS-5 is a major aggrecanase in cartilage metabolism and pathology, with aggrecanase activity at least 1,000-fold greater than that of ADAMTS-4 under physiological conditions (PMID:17430884)
• In both nucleus pulposis and anulus fibrosus, ADAMTS5 was higher in discs with a higher level of degeneration. Aggrecan fragmentation profile analysis showed the involvement of aggrecanases and other proteases during disc degeneration. (PMID:17978660)
• The catalytic domain of aggrecanase-2 has been refolded, purified, and crystallized, and its three-dimensional structure determined to 1.4A resolution in the presence of an inhibitor. (PMID:17991750)
• Crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhiitor. (PMID:18042673)
• the catalytic domain of ADAMTS-5 has higher intrinsic catalytic ability than that of ADAMTS-4 (PMID:18156631)
• evidence against the participation of genetic variation in ADAMTS-5 in osteoarthritis susceptibility (PMID:18240210)
• identified a regulatory region associated with the gene ADAMTS5 that encompasses the entirety of the essential coding exon 2 (PMID:18478108)
• PACE4 is a proprotein convertase responsible for activation of aggrecanases in osteoarthritic and cytokine-stimulated cartilage; posttranslational activation of ADAMTS-4 and ADAMTS-5 in the extracellular milieu of cartilage results in aggrecan degradation (PMID:18671934)
• ADAMTS-5 is related to deformation and destruction of human TMJ discs affected by internal derangement (ID) and osteoarthritis (PMID:18830934)
• The C-terminal domains of ADAMTS-4 and ADAMTS-5 affect the structure around the active site, favouring interaction with TIMP-3. (PMID:19643179)
• Syndecan-4 controls the activation of ADAMTS-5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix metalloproteinase-3 (MMP-3). (PMID:19684582)
• The ADAMTS5 promoter is activated by serum depletion according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
• four of the six aggrecanases are expressed in immortalized chondrocyte cell-lines and can be upregulated in response to inflammatory cytokines (PMID:20568084)
• ADAMTS-5 is present in human coronary atherosclerotic plaques. (PMID:21345877)
• Structure analysis with a succinamide inhibitor reveals the flexibility of the ADAMTS-5 active site. (PMID:21370305)
• ADAMTS-5 is probably involved in the process of herniated intervertebral disc degeneration, and that IL-1beta-induced expression of ADAMTS-5 is mediated by NO. (PMID:21437951)
• a physiological function of ADAMTS5 in dermal fibroblasts is to maintain optimal versican content and PCM volume by continually trimming versican in hyaluronan-versican aggregates. (PMID:21828051)
• the first evidence implicating ADAMTS-5 in the regulation of proteoglycan turnover and lipoprotein retention in atherosclerosis. (PMID:22493487)
• Data show that the expression of ADAMTS4, 9, 16 and was up-regulated during chondrogenesis, ADAMTS1 and 5 were down-regulated. (PMID:22562232)
• chimeric proteases and substrates to examine the role of C-terminal domains of ADAMTS13 and ADAMTS5 in the recognition of their physiological cleavage sites in von Willebrand factor (VWF) and aggrecan, respectively (PMID:22707719)
• study showed that ADAMTS-1, -4, -5 and TIMP3 were expressed at differential levels in hepatocellular carcinoma cell lines (PMID:22735305)
• This is the first report that ADAMTS5 is an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity. (PMID:22796434)
• Our results suggest that the ADAMTS5 gene polymorphisms may contribute to the susceptibility of osteoarthritis in the Chinese Han population. (PMID:22961118)
• LRP-1 dictates physiological and pathological catabolism of aggrecan in cartilage as a key modulator of the extracellular activity of ADAMTS-5. (PMID:23064555)
• The serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, were identified as Reelin cleaving enzymes. (PMID:23082219)
• ADAMTS-5/aggrecanase-2 is the main aggrecanase present in laryngeal carcinoma (PMID:23131589)
• The present study reveals ADAMT-5 expression by mast cells(MCs) and that MC activation regulates the expression of the protease, thus implicating the ADAMT-5 of protease in MC function. (PMID:23154421)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts5	ENSDARG00000100307
mus_musculus	Adamts5	ENSMUSG00000022894
rattus_norvegicus	Adamts5	ENSRNOG00000057794

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 5 — Q9UNA0 (reviewed: Q9UNA0)

Alternative names: A disintegrin and metalloproteinase with thrombospondin motifs 11, ADMP-2, Aggrecanase-2

All UniProt accessions (2): Q9UNA0, A0A494C1E4

UniProt curated annotations — full annotation on UniProt →

Function. Metalloproteinase that plays an important role in connective tissue organization, development, inflammation and cell migration. Extracellular matrix (ECM) degrading enzyme that show proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including ACAN, VCAN, BCAN and NCAN. Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle development through its VCAN remodeling properties. Cleaves VCAN in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion which is required for skeletal muscle development and regeneration. Participates in development of brown adipose tissue and browning of white adipose tissue. Plays an important role for T-lymphocyte migration from draining lymph nodes following viral infection.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed at low level in placenta primarily but also detected in heart and brain, cervix, uterus, bladder, esophagus, rib cartilage, chondroblastoma, fibrous tissue and a joint capsule from an arthritic patient.

Post-translational modifications. The precursor is cleaved by furin and PCSK7 outside of the cell. Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix. 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.

RefSeq proteins (1): NP_008969* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR013276	Pept_M12B_ADAM-TS5	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR041645	ADAMTS_CR_2	Domain
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF01421, PF05986, PF17771, PF19030, PF19236

Enzyme classification (BRENDA):

• EC 3.4.24.B12 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (72 total): strand 15, helix 13, disulfide bond 11, glycosylation site 7, binding site 4, domain 4, sequence variant 3, turn 3, region of interest 3, compositionally biased region 2, signal peptide 1, propeptide 1, short sequence motif 1, active site 1, site 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3B8Z	X-RAY DIFFRACTION	1.4
3HYG	X-RAY DIFFRACTION	1.4
3LJT	X-RAY DIFFRACTION	1.6
3HY7	X-RAY DIFFRACTION	1.69
3HY9	X-RAY DIFFRACTION	2.02
6YJM	X-RAY DIFFRACTION	2.25
2RJQ	X-RAY DIFFRACTION	2.6
9RWM	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNA0-F1	78.07	0.43

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 (2): 411; 261 (cleavage; by furin and pcsk7)

Ligand- & substrate-binding residues (4): 209 (in inhibited form); 410; 414; 420

Disulfide bonds (11): 342–394, 371–376, 388–471, 426–455, 497–519, 508–529, 514–548, 542–553, 579–616, 583–621, 594–606

Glycosylation sites (7): 498, 570, 573, 582, 728, 802, 807

Mutagenesis-validated functional residues (1):

Position	Phenotype
411	complete loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-1474244	Extracellular matrix organization
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 302 (showing top): BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ATGCAGT_MIR217, GGGTGGRR_PAX4_03, LIEN_BREAST_CARCINOMA_METAPLASTIC, GOBP_ENDOCARDIAL_CUSHION_MORPHOGENESIS, CEBPB_01, TANG_SENESCENCE_TP53_TARGETS_UP, RODRIGUES_NTN1_TARGETS_DN, NFKB_Q6

GO Biological Process (9): aortic valve morphogenesis (GO:0003180), pulmonary valve morphogenesis (GO:0003184), endocardial cushion morphogenesis (GO:0003203), proteolysis (GO:0006508), myoblast fusion (GO:0007520), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), defense response to bacterium (GO:0042742), negative regulation of cold-induced thermogenesis (GO:0120163)

GO Molecular Function (12): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), integrin binding (GO:0005178), heparin binding (GO:0008201), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), extracellular matrix binding (GO:0050840), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Extracellular matrix organization	1
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
heart valve morphogenesis	2
peptidase activity	2
binding	2
aortic valve development	1
pulmonary valve development	1
heart morphogenesis	1
endocardial cushion development	1
mesenchyme morphogenesis	1
protein metabolic process	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
cellular component disassembly	1
extracellular matrix organization	1
extracellular structure organization	1
external encapsulating structure organization	1
defense response	1
response to bacterium	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
endopeptidase activity	1
metallopeptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
protein binding	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS5	ACAN	P16112	955
ADAMTS5	SDC4	P31431	933
ADAMTS5	MMP13	P45452	897
ADAMTS5	MMP3	P08254	883
ADAMTS5	TIMP3	P35625	837
ADAMTS5	COL2A1	P02458	805
ADAMTS5	RUNX2	Q13950	741
ADAMTS5	IL1B	P01584	738
ADAMTS5	TIMP1	P01033	732
ADAMTS5	IHH	Q14623	706
ADAMTS5	SOX9	P48436	685
ADAMTS5	BCAN	Q96GW7	669
ADAMTS5	COL10A1	Q03692	647
ADAMTS5	FURIN	P09958	639
ADAMTS5	MMP1	P03956	635

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ADAMTS5		psi-mi:“MI:0194”(cleavage reaction)	0.440
ACAN	ADAMTS5	psi-mi:“MI:0570”(protein cleavage)	0.440
ADAMTS5	ACAN	psi-mi:“MI:0570”(protein cleavage)	0.440
PBK	ADAMTS5	psi-mi:“MI:0915”(physical association)	0.400
ADAMTS5		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): ADAMTS5 (Affinity Capture-RNA), ADAMTS5 (Affinity Capture-MS), ADAMTS5 (Cross-Linking-MS (XL-MS)), ADAMTS5 (Cross-Linking-MS (XL-MS)), ADAMTS5 (Proximity Label-MS)

ESM2 similar proteins: A0A0N9E2K8, A0A1D5NSK0, A0A8M9PFP2, G5ECS8, G5EFD9, O15072, O18767, O43909, O60882, O62806, O77656, O93470, P07152, P22003, P23097, P28825, P29788, P33435, P49003, P57748, P79287, Q10835, Q11005, Q14703, Q16819, Q16820, Q19791, Q24025, Q3U435, Q568B8, Q61847, Q64230, Q6GQB9, Q6NP60, Q8CGD2, Q8K3F2, Q8N119, Q8R4K8, Q8VDA1, Q90YC2

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SIRT1	“down-regulates quantity by repression”	ADAMTS5	“transcriptional regulation”
ADAMTS5	“down-regulates quantity by destabilization”	ACAN	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	143
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1442 predictions. Top by Δscore:

Variant	Effect	Δscore
21:26924656:G:C	acceptor_gain	1.0000
21:26924656:G:GC	acceptor_gain	1.0000
21:26924660:T:C	acceptor_gain	1.0000
21:26924660:T:TC	acceptor_gain	1.0000
21:26932175:TTTAC:T	acceptor_gain	1.0000
21:26932176:TTAC:T	acceptor_gain	1.0000
21:26932177:TAC:T	acceptor_gain	1.0000
21:26932179:CCTA:C	acceptor_loss	1.0000
21:26932857:GTACC:G	donor_loss	1.0000
21:26932858:TACC:T	donor_loss	1.0000
21:26932859:ACCAT:A	donor_loss	1.0000
21:26932860:C:CG	donor_loss	1.0000
21:26932909:T:TA	donor_gain	1.0000
21:26932910:C:A	donor_gain	1.0000
21:26933042:CGT:C	acceptor_gain	1.0000
21:26933045:C:CC	acceptor_gain	1.0000
21:26934521:C:A	donor_gain	1.0000
21:26943544:TGTCC:T	acceptor_loss	1.0000
21:26943548:C:CA	acceptor_loss	1.0000
21:26943549:T:A	acceptor_loss	1.0000
21:26954733:GCATA:G	donor_loss	1.0000
21:26954734:CATAC:C	donor_loss	1.0000
21:26954735:ATACC:A	donor_loss	1.0000
21:26954736:TA:T	donor_loss	1.0000
21:26954737:A:AC	donor_gain	1.0000
21:26954737:ACC:A	donor_loss	1.0000
21:26954738:C:CC	donor_gain	1.0000
21:26954738:C:T	donor_loss	1.0000
21:26954867:AAATC:A	acceptor_gain	1.0000
21:26954870:TC:T	acceptor_gain	1.0000

AlphaMissense

6016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:26924209:C:A	W879C	1.000
21:26924209:C:G	W879C	1.000
21:26932059:C:G	C665S	1.000
21:26932060:A:T	C665S	1.000
21:26932097:C:A	W652C	1.000
21:26932097:C:G	W652C	1.000
21:26932099:A:G	W652R	1.000
21:26932099:A:T	W652R	1.000
21:26932155:C:G	C633S	1.000
21:26932156:A:T	C633S	1.000
21:26932916:G:C	C606W	1.000
21:26932917:C:G	C606S	1.000
21:26932918:A:T	C606S	1.000
21:26932953:C:G	C594S	1.000
21:26932954:A:T	C594S	1.000
21:26933015:C:A	W573C	1.000
21:26933015:C:G	W573C	1.000
21:26933024:C:A	W570C	1.000
21:26933024:C:G	W570C	1.000
21:26934497:C:G	C553S	1.000
21:26934498:A:G	C553R	1.000
21:26934498:A:T	C553S	1.000
21:26934511:G:C	C548W	1.000
21:26934512:C:G	C548S	1.000
21:26934513:A:G	C548R	1.000
21:26934513:A:T	C548S	1.000
21:26934530:C:G	C542S	1.000
21:26934531:A:T	C542S	1.000
21:26934569:C:G	C529S	1.000
21:26934570:A:G	C529R	1.000

dbSNP variants (sampled 300 via entrez): RS1000043021 (21:26953836 C>T), RS1000137267 (21:26926139 C>T), RS1000219491 (21:26966832 C>G), RS1000236564 (21:26964964 A>T), RS1000244553 (21:26960570 T>C), RS1000281202 (21:26951806 CA>C,CAA), RS1000342091 (21:26930094 A>G), RS1000375886 (21:26947356 A>T), RS1000413380 (21:26923370 G>A), RS1000440459 (21:26966557 G>A,C), RS1000469679 (21:26960773 T>C), RS1000531302 (21:26938677 G>A), RS1000562216 (21:26929824 A>C,T), RS1000641170 (21:26923701 T>C), RS1000742404 (21:26927520 T>C)

Disease associations

OMIM: gene MIM:605007 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001066_6	Dialysis-related mortality	2.000000e-06
GCST001066_9	Dialysis-related mortality	4.000000e-06
GCST006585_397	Blood protein levels	1.000000e-249
GCST008367_3	Plasma anti-thyroglobulin and anti-thyroid peroxidase levels (bivariate analysis)	4.000000e-06
GCST008839_247	Height	2.000000e-10
GCST010216_2	Diastolic blood pressure	9.000000e-06
GCST010796_4549	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_4550	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_4576	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST90020029_159	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006945	diastolic blood pressure change measurement
EFO:0004327	electrocardiography
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2285 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 87,932 (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
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL19611	ILOMASTAT	2	12,065
CHEMBL4650334	ALDUMASTAT	2	58
CHEMBL4859268	AGG-523	1	35

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
aldumastat	Inhibition	7.72	pIC50
compound 15c [PMID: 21536437]	Inhibition	7.7	pIC50

Binding affinities (BindingDB)

333 measured of 588 human assays (588 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(4R)-4-[3-(dimethylamino)propyl]-1-(2-fluoro-5-methylphenyl)-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	0.2 nM
1-[1-(2,5-difluorophenyl)-4-{3-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propyl}-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	1.2 nM
1-[(5R,6R)-5-[3-(4-acetylpiperazin-1-yl)propyl]-12-fluoro-5-phenyl-8-oxa-2,3-diazatricyclo[7.4.0.0^{2,6}]trideca-1(9),3,10,12-tetraen-4-yl]ethan-1-one	IC50	1.6 nM
(5S)-5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide	IC50	1.9 nM
(2S)-2-amino-2-cyclopropyl-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]ethan-1-one	IC50	2 nM
1-{4-[3-(4-acetylpiperazin-1-yl)propyl]-1-(2-fluoro-5-methylphenyl)-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl}ethan-1-one	IC50	2 nM
5-[3-[4-(4-chloro-3,5-difluorophenyl)piperazin-1-yl]-2-methyl-3-oxopropyl]-5-(methoxymethyl)imidazolidine-2,4-dione	IC50	2 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
1-[1-(2,5-difluorophenyl)-4-[3-(dimethylamino)propyl]-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	2.1 nM
(2S)-4-(2,5-difluorophenyl)-N-methyl-2-phenyl-N-(piperidin-4-yl)-2,5-dihydro-1H-pyrrole-1-carboxamide	IC50	2.6 nM
(2S)-2-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-3,3-dimethylbutan-1-one	IC50	2.7 nM
(2S)-2-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-3-methylbutan-1-one	IC50	3.6 nM
1-[1-(2,5-difluorophenyl)-4-[3-(4-acetylpiperazin-1-yl)propyl]-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	3.8 nM
1-[1-(2,5-difluorophenyl)-4-phenyl-4-[3-(pyrrolidin-1-yl)propyl]-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	3.8 nM
Racemate	IC50	3.9 nM
1-[1-(2,5-difluorophenyl)-4-(3-{methyl[(3-methyl-1,2-oxazol-5-yl)methyl]amino}propyl)-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	4 nM
1-[1-(2,5-difluorophenyl)-4-[3-(morpholin-4-yl)propyl]-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	4.2 nM
Racemate	IC50	4.7 nM
3-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2,2-dimethylpropan-1-one	IC50	5.2 nM
1-[1-(2,5-difluorophenyl)-4-[3-(3-fluoroazetidin-1-yl)propyl]-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl]ethan-1-one	IC50	5.2 nM
2-hydroxyethyl N-[(2S)-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate	IC50	7.4 nM
5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide	IC50	8 nM
Racemate	IC50	10.1 nM
(2S)-2-cyclopropyl-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-hydroxyethan-1-one	IC50	11 nM
(2S)-N-(3-aminopropyl)-4-(2,5-difluorophenyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide	IC50	16 nM
Racemate	IC50	16.5 nM
1-{4-[3-(4-acetylpiperazin-1-yl)propyl]-1-(2-fluorophenyl)-4-phenyl-4,5-dihydro-1H-pyrazol-3-yl}ethan-1-one	IC50	21.8 nM
1-[(5S)-3-(2,5-difluorophenyl)-5-(3-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethan-1-one	IC50	24.7 nM
3-[3-(2,5-difluorophenyl)-5-phenyl-1-(pyrrolidin-1-ylcarbonyl)-4,5-dihydro-1H-pyrazol-5-yl]propan-1-amine	IC50	26 nM
5-[3-[4-(4-chloro-3-fluorophenyl)piperazin-1-yl]-3-oxopropyl]-5-phenylimidazolidine-2,4-dione	IC50	26 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
(2S)-4-(2,5-difluorophenyl)-N,N-dimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide	IC50	38 nM
5-[3-(4-isoquinolin-6-ylpiperazin-1-yl)-3-oxopropyl]-5-phenylimidazolidine-2,4-dione	IC50	38 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-[3-[4-(3,4-difluorophenyl)piperazin-1-yl]-2-methyl-3-oxopropyl]-5-(methoxymethyl)imidazolidine-2,4-dione	IC50	38 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N-ethyl-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide	IC50	44 nM
Inhibitor, 18	KI	47 nM
(2S)-4-(2,5-difluorophenyl)-N-(1-acetylpiperidin-4-yl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide	IC50	50 nM
5-[3-[(3S)-4-(4-chloro-3,5-difluorophenyl)-3-methylpiperazin-1-yl]-2-methyl-3-oxopropyl]-5-(methoxymethyl)imidazolidine-2,4-dione	IC50	53 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
3-[1-(azetidin-1-ylcarbonyl)-3-(2,5-difluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-5-yl]propan-1-amine	IC50	55 nM
Inhibitor, 17	KI	57 nM
5-[3-[(3S)-4-(4-chlorophenyl)-3-methylpiperazin-1-yl]-2-methyl-3-oxopropyl]-5-cyclopropylimidazolidine-2,4-dione	IC50	63 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
5-(4-aminobutyl)-3-(2,5-difluorophenyl)-N-ethyl-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide	IC50	67 nM
(1R,2S)-1-{[4-(4-chlorophenyl)benzene][2-(7H-purin-7-yl)ethyl]sulfonamido}-2-phenylcyclopropane-1-carboxylic acid	IC50	71 nM
(1R,2S)-1-{4-(4-chlorophenyl)benzenesulfonamido}-2-phenylcyclopropane-1-carboxylic acid	IC50	73 nM
(1R,2S)-1-{[4-(4-chlorophenyl)benzene][2-(3-methoxy-2-oxo-1,2-dihydropyridin-1-yl)ethyl]sulfonamido}-2-phenylcyclopropane-1-carboxylic acid	IC50	78 nM
5-cyclopropyl-5-[3-[4-(3-fluorophenyl)-3-methylpiperazin-1-yl]-3-oxopropyl]imidazolidine-2,4-dione	IC50	79 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
(1S,2R)-1-(5-(4-chloro-1H-pyrazol-1-yl)thiophene-2-sulfonamido)-2-phenylcyclopropanecarboxylic acid	IC50	80 nM	US-10322143: Inhibitors of ADAMTS4 or ADAMTS5 for use in preventing or treating cardiac remodeling and chronic heart failure
5-[3-[4-(4-chloro-3-fluorophenyl)piperazin-1-yl]-3-oxopropyl]-5-methylimidazolidine-2,4-dione	IC50	83 nM	US-9926281: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as ADAMTS inhibitors for the treatment of osteoarthritis
3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide	IC50	84 nM
(1S,2R)-1-(4’-chlorobiphenyl-4-ylsulfonamido)-2-phenylcyclopropanecarboxylic acid	IC50	84 nM	US-10322143: Inhibitors of ADAMTS4 or ADAMTS5 for use in preventing or treating cardiac remodeling and chronic heart failure
1-[4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2,2-dimethylpropan-1-one	IC50	85 nM
3-[3-(2,5-difluorophenyl)-5-phenyl-1-(piperidin-1-ylcarbonyl)-4,5-dihydro-1H-pyrazol-5-yl]propan-1-amine	IC50	85 nM

ChEMBL bioactivities

1109 potent at pChembl≥5 of 1144 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL187092
9.00	IC50	1	nM	CHEMBL4066965
8.85	IC50	1.4	nM	CHEMBL179552
8.70	IC50	2	nM	CHEMBL4072836
8.70	IC50	2	nM	CHEMBL3980860
8.54	IC50	2.9	nM	CHEMBL1766903
8.52	IC50	3	nM	CHEMBL3358156
8.52	IC50	3	nM	CHEMBL4436740
8.52	Ki	3	nM	CHEMBL5595366
8.52	Ki	3	nM	CHEMBL5589746
8.40	IC50	4	nM	CHEMBL3358158
8.40	IC50	4	nM	CHEMBL3972836
8.40	IC50	4	nM	CHEMBL4450729
8.30	IC50	5	nM	CHEMBL4102193
8.30	IC50	5	nM	CHEMBL4097165
8.22	Ki	6	nM	CHEMBL5591230
8.20	IC50	6.3	nM	CHEMBL187092
8.15	IC50	7	nM	CHEMBL4587825
8.13	IC50	7.4	nM	CHEMBL1078281
8.10	IC50	8	nM	CHEMBL3955404
8.10	IC50	8	nM	CHEMBL4864283
8.08	IC50	8.3	nM	CHEMBL1766904
8.08	IC50	8.4	nM	CHEMBL1767014
8.07	IC50	8.6	nM	CHEMBL1767011
8.05	IC50	9	nM	CHEMBL3358156
8.05	IC50	9	nM	CHEMBL4589438
8.05	Ki	9	nM	CHEMBL5594088
8.00	Ki	10	nM	CHEMBL5593176
8.00	IC50	10	nM	CHEMBL1078454
8.00	IC50	10	nM	CHEMBL1766905
8.00	IC50	10	nM	CHEMBL1767015
7.96	IC50	11	nM	CHEMBL5769726
7.96	IC50	11	nM	CHEMBL5851590
7.96	IC50	11	nM	CHEMBL1784336
7.92	IC50	12	nM	CHEMBL4874034
7.92	IC50	12	nM	CHEMBL6023444
7.92	IC50	12	nM	CHEMBL24398
7.90	IC50	12.5	nM	CHEMBL5838438
7.90	IC50	12.5	nM	CHEMBL5841723
7.90	IC50	12.5	nM	CHEMBL5891291
7.90	IC50	12.5	nM	CHEMBL5851756
7.90	IC50	12.5	nM	CHEMBL5740606
7.90	IC50	12.5	nM	CHEMBL5787381
7.90	IC50	12.5	nM	CHEMBL5914760
7.90	IC50	12.5	nM	CHEMBL5933095
7.90	IC50	12.5	nM	CHEMBL5939068
7.90	IC50	12.5	nM	CHEMBL5772350
7.90	IC50	12.5	nM	CHEMBL5968483
7.90	IC50	12.5	nM	CHEMBL5793433
7.90	IC50	12.5	nM	CHEMBL5834069

PubChem BioAssay actives

634 with measured affinity, of 837 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
1-[(4R)-4-[3-(dimethylamino)propyl]-2-(2-fluoro-5-methylphenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0002	uM
(2R,3R)-1-[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonyl-N,3-dihydroxy-3-methylpiperidine-2-carboxamide	1171556: Inhibition of human ADAMTS-5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide substrate by AlphaScreen assay	ic50	0.0010	uM
(2R)-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-2-methyl-3-[4-(trifluoromethyl)phenyl]propanamide	1445578: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs by Alphascreen assay	ic50	0.0010	uM
1-[2-(2,5-difluorophenyl)-4-[3-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0012	uM
(2R,5R)-1-[4-[(2,4-dichlorophenyl)methoxy]phenyl]sulfonyl-N,5-dihydroxy-3,3-dimethylpiperidine-2-carboxamide	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0014	uM
1-[(3R,3aR)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0016	uM
(5S)-5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-4H-pyrazole-1-carboxamide	1798396: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.03.040: “Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP.”	ic50	0.0019	uM
1-[4-[3-(4-acetylpiperazin-1-yl)propyl]-2-(2-fluoro-5-methylphenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0020	uM
(2S)-2-amino-2-cyclopropyl-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydropyrrol-1-yl]ethanone	1798394: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.01.030: “Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.”	ic50	0.0020	uM
(2R)-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-2-[[4-(trifluoromethyl)phenyl]methyl]butanamide	1445578: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs by Alphascreen assay	ic50	0.0020	uM
(2S)-2-cyclopropyl-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-3-[4-(trifluoromethyl)phenyl]propanamide	1445578: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs by Alphascreen assay	ic50	0.0020	uM
1-[2-(2,5-difluorophenyl)-4-[3-(dimethylamino)propyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0021	uM
(2S)-4-(2,5-difluorophenyl)-N-methyl-2-phenyl-N-piperidin-4-yl-2,5-dihydropyrrole-1-carboxamide	1798394: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.01.030: “Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.”	ic50	0.0026	uM
(2S)-2-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydropyrrol-1-yl]-3,3-dimethylbutan-1-one	1798394: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.01.030: “Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.”	ic50	0.0027	uM
(1S,2R,3R)-1-[(6-chloro-4H-thieno[3,2-b]indol-2-yl)sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0029	uM
N-[[(4S)-4-(1,5-dimethylimidazol-2-yl)-2,5-dioxoimidazolidin-4-yl]methyl]-5-(trifluoromethyl)-1-benzofuran-2-carboxamide	1625615: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay	ic50	0.0030	uM
N-[4-[[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-3-methyl-5-oxopentyl]benzamide	2114992: Inhibition of recombinant human full-length ADAMTS5 using FAM-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-Lys-Lys-TAMRA as substrate by FRET assay	ki	0.0030	uM
1-benzoyl-4-[[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxypiperidine-4-carboxamide	2114992: Inhibition of recombinant human full-length ADAMTS5 using FAM-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-Lys-Lys-TAMRA as substrate by FRET assay	ki	0.0030	uM
5-chloro-N-[[(4S)-4-(1-methylimidazol-2-yl)-2,5-dioxoimidazolidin-4-yl]methyl]-1-benzofuran-2-carboxamide	1625615: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay	ic50	0.0030	uM
(2S)-2-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydropyrrol-1-yl]-3-methylbutan-1-one	1798394: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.01.030: “Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.”	ic50	0.0036	uM
1-[4-[3-(4-acetylpiperazin-1-yl)propyl]-2-(2,5-difluorophenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0038	uM
1-[2-(2,5-difluorophenyl)-4-phenyl-4-(3-pyrrolidin-1-ylpropyl)-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0038	uM
1-[4-[3-(4-acetylpiperazin-1-yl)propyl]-2-(5-chloro-2-fluorophenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0039	uM
N-[[(4S)-4-(1-methylimidazol-2-yl)-2,5-dioxoimidazolidin-4-yl]methyl]-5-(trifluoromethyl)-1-benzofuran-2-carboxamide	1171556: Inhibition of human ADAMTS-5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide substrate by AlphaScreen assay	ic50	0.0040	uM
N-[[(4S)-4-(1-ethylimidazol-2-yl)-2,5-dioxoimidazolidin-4-yl]methyl]-5-(trifluoromethyl)-1-benzofuran-2-carboxamide	1625615: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay	ic50	0.0040	uM
1-[2-(2,5-difluorophenyl)-4-[3-[methyl-[(3-methyl-1,2-oxazol-5-yl)methyl]amino]propyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0040	uM
N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-2,2-dimethyl-3-[4-(trifluoromethyl)phenyl]propanamide	1445578: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs by Alphascreen assay	ic50	0.0040	uM
1-[2-(2,5-difluorophenyl)-4-(3-morpholin-4-ylpropyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0042	uM
1-[4-[3-(4-acetylpiperazin-1-yl)propyl]-2-(5-bromo-2-fluorophenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0047	uM
N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-5-(trifluoromethyl)-1-benzofuran-2-carboxamide	1625615: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay	ic50	0.0050	uM
N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-3-[4-(trifluoromethyl)phenyl]propanamide	1445578: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs by Alphascreen assay	ic50	0.0050	uM
3-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydropyrrol-1-yl]-2,2-dimethylpropan-1-one	1798394: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.01.030: “Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.”	ic50	0.0052	uM
1-[2-(2,5-difluorophenyl)-4-[3-(3-fluoroazetidin-1-yl)propyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0052	uM
(2R)-2-(1-benzoylpiperidin-4-yl)-2-[[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxyacetamide	2114992: Inhibition of recombinant human full-length ADAMTS5 using FAM-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-Lys-Lys-TAMRA as substrate by FRET assay	ki	0.0060	uM
5-chloro-N-[[(4S)-4-(1,5-dimethylimidazol-2-yl)-2,5-dioxoimidazolidin-4-yl]methyl]-1-benzofuran-2-carboxamide	1625615: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay	ic50	0.0070	uM
2-hydroxyethyl N-[(2S)-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydropyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate	1798394: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.01.030: “Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.”	ic50	0.0074	uM
(1S,2R,3R)-1-[[5-(4-chloropyrazol-1-yl)thiophen-2-yl]sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	468965: Inhibition of ADAMTS5	ic50	0.0074	uM
trans-(1S,2R)-1-[(11-fluoro-1,5,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-5-yl)sulfonylamino]-2,3-dimethyl-2-phenylcyclopropane-1-carboxylic acid	1775762: Inhibition of human recombinant ADAMTS5 using synthetic peptide as substrate by FRET assay	ic50	0.0080	uM
5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-4H-pyrazole-1-carboxamide	1798396: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2006.03.040: “Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP.”	ic50	0.0080	uM
(2S)-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-3-methyl-2-[[4-(trifluoromethyl)phenyl]methyl]butanamide	1445578: Inhibition of human ADAMTS5 using VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG peptide as substrate after 3 hrs by Alphascreen assay	ic50	0.0080	uM
(1S,2R,3R)-1-[(6-fluoro-4H-thieno[3,2-b]indol-2-yl)sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0083	uM
(1S,2R,3R)-1-[(11-fluoro-1,5,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-5-yl)sulfonylamino]-2,3-dimethyl-2-phenylcyclopropane-1-carboxylic acid	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0084	uM
(1S,2R,3R)-1-[(11-fluoro-5,8,9-triazatricyclo[7.4.0.02,7]trideca-1,7,10,12-tetraen-5-yl)sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0086	uM
5-chloro-N-[[(4S)-4-(1-ethylimidazol-2-yl)-2,5-dioxoimidazolidin-4-yl]methyl]-1-benzofuran-2-carboxamide	1625615: Inhibition of human ADAMTS5 using 43-mer VQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLKG as substrate measured after 3 hrs by AlphaScreen assay	ic50	0.0090	uM
(2R)-3-(1-benzoylpiperidin-4-yl)-2-[[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxypropanamide	2114992: Inhibition of recombinant human full-length ADAMTS5 using FAM-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-Lys-Lys-TAMRA as substrate by FRET assay	ki	0.0090	uM
N-[(4R)-4-[[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]benzamide	2114992: Inhibition of recombinant human full-length ADAMTS5 using FAM-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-Lys-Lys-TAMRA as substrate by FRET assay	ki	0.0100	uM
trans-(1S,2R)-1-[[5-(4-chlorophenyl)thiophen-2-yl]sulfonylamino]-2-methyl-2-phenylcyclopropane-1-carboxylic acid	468965: Inhibition of ADAMTS5	ic50	0.0100	uM
(1S,2R,3R)-1-[(7-fluoro-4H-thieno[3,2-b]indol-2-yl)sulfonylamino]-2-methyl-3-phenylcyclopropane-1-carboxylic acid	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0100	uM
(1S,2R,3R)-1-[(11-fluoro-5,8,9-triazatricyclo[7.4.0.02,7]trideca-1,7,10,12-tetraen-5-yl)sulfonylamino]-2,3-dimethyl-2-phenylcyclopropane-1-carboxylic acid	593447: Inhibition of human recombinant aggrecanase 2 after 150 mins by fluorescence plate reader	ic50	0.0100	uM
1-[4-[3-(4-acetylpiperazin-1-yl)propyl]-2-[2-fluoro-5-(trifluoromethyl)phenyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	1798398: Kinesin ATPase In Vitro Assay from Article 10.1016/j.bmcl.2007.07.074: “Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.”	ic50	0.0101	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Glucosamine	decreases expression, decreases activity, decreases cleavage	2
Nickel	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases methylation, affects cotreatment	1
N-((3,5-difluorophenyl)acetyl)alanyl-2-phenylglycine-1,1-dimethylethyl ester	decreases expression	1
stachydrine	decreases reaction, increases secretion	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
mannosamine	decreases cleavage	1
HT-2 toxin	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
glucosamine 3-O-sulfate	decreases expression	1
chromium hexavalent ion	affects expression	1
2-phenylcyclopropanecarboxylic acid	decreases activity, affects binding	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
dulaglutide	decreases reaction, increases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	increases expression	1

ChEMBL screening assays

73 unique, capped per target: 72 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005373	Binding	Inhibition of ADAMTS5	Synthesis of a 200-member library of squaric acid N-hydroxylamide amides. — Bioorg Med Chem Lett
CHEMBL5579508	Toxicity	Inhibition of recombinant human full-length ADAMTS5 using FAM-Thr-Glu-Ser-Glu-Ser-Arg-Gly-Ala-Ile-Tyr-Lys-Lys-TAMRA as substrate by FRET assay	Design, synthesis and biological evaluation of arylsulfonamides as ADAMTS7 inhibitors. — RSC Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists