Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTXSU2Y)

DTT Name	Aggrecanase (ADAMTS5)
Synonyms	Aggrecanase-2; ADMP-2; ADAMTS5; ADAMTS-5; ADAM-TS5; ADAM-TS 5; ADAM-TS 11; A disintegrin and metalloproteinase with thrombospondinmotifs 5
Gene Name	ADAMTS5
DTT Type	Clinical trial target	[1]
BioChemical Class	Peptidase
UniProt ID	ATS5_HUMAN
TTD ID	T98896
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 3.4.24.-
Sequence	MLLGWASLLLCAFRLPLAAVGPAATPAQDKAGQPPTAAAAAQPRRRQGEEVQERAEPPGH PHPLAQRRRSKGLVQNIDQLYSGGGKVGYLVYAGGRRFLLDLERDGSVGIAGFVPAGGGT SAPWRHRSHCFYRGTVDGSPRSLAVFDLCGGLDGFFAVKHARYTLKPLLRGPWAEEEKGR VYGDGSARILHVYTREGFSFEALPPRASCETPASTPEAHEHAPAHSNPSGRAALASQLLD QSALSPAGGSGPQTWWRRRRRSISRARQVELLLVADASMARLYGRGLQHYLLTLASIANR LYSHASIENHIRLAVVKVVVLGDKDKSLEVSKNAATTLKNFCKWQHQHNQLGDDHEEHYD AAILFTREDLCGHHSCDTLGMADVGTICSPERSCAVIEDDGLHAAFTVAHEIGHLLGLSH DDSKFCEETFGSTEDKRLMSSILTSIDASKPWSKCTSATITEFLDDGHGNCLLDLPRKQI LGPEELPGQTYDATQQCNLTFGPEYSVCPGMDVCARLWCAVVRQGQMVCLTKKLPAVEGT PCGKGRICLQGKCVDKTKKKYYSTSSHGNWGSWGSWGQCSRSCGGGVQFAYRHCNNPAPR NNGRYCTGKRAIYRSCSLMPCPPNGKSFRHEQCEAKNGYQSDAKGVKTFVEWVPKYAGVL PADVCKLTCRAKGTGYYVVFSPKVTDGTECRLYSNSVCVRGKCVRTGCDGIIGSKLQYDK CGVCGGDNSSCTKIVGTFNKKSKGYTDVVRIPEGATHIKVRQFKAKDQTRFTAYLALKKK NGEYLINGKYMISTSETIIDINGTVMNYSGWSHRDDFLHGMGYSATKEILIVQILATDPT KPLDVRYSFFVPKKSTPKVNSVTSHGSNKVGSHTSQPQWVTGPWLACSRTCDTGWHTRTV QCQDGNRKLAKGCPLSQRPSAFKQCLLKKC
Function	Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period.
Reactome Pathway	O-glycosylation of TSR domain-containing proteins (R-HSA-5173214 ) Degradation of the extracellular matrix (R-HSA-1474228 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

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1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AGG-523	DMVMIBY	Osteoarthritis	FA00-FA05	Phase 1	[1]
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1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SC-44463	DMBPNKT	N. A.	N. A.	Terminated	[2]
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2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CR-5259	DME5IJQ	Osteoarthritis	FA00-FA05	Investigative	[3]
PMID21536437C15c	DM2R94W	Discovery agent	N.A.	Investigative	[4]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Osteoarthritis	FA20	Synovial tissue	6.40E-01	0.24	0.26
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References

1	Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor. Osteoarthritis Cartilage. 2011 Mar;19(3):315-23.
2	Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivati... J Med Chem. 2001 Oct 11;44(21):3347-50.
3	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1677).
4	Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3301-6.