Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTYG6BU)

• DTT Name: Aggrecanase-1 (ADAMTS4)
• Synonyms: Aggrecanase 1; ADMP-1; ADAMTS4; ADAM-TS4; ADAM-TS 4; A disintegrin and metalloproteinase with thrombospondin motifs 4
• Gene Name: ADAMTS4
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Peptidase
• UniProt ID: ATS4_HUMAN
• TTD ID: T79570
• EC Number: EC 3.4.24.82
• Sequence:
  MSQTGSHPGRGLAGRWLWGAQPCLLLPIVPLSWLVWLLLLLLASLLPSARLASPLPREEE
  IVFPEKLNGSVLPGSGAPARLLCRLQAFGETLLLELEQDSGVQVEGLTVQYLGQAPELLG
  GAEPGTYLTGTINGDPESVASLHWDGGALLGVLQYRGAELHLQPLEGGTPNSAGGPGAHI
  LRRKSPASGQGPMCNVKAPLGSPSPRPRRAKRFASLSRFVETLVVADDKMAAFHGAGLKR
  YLLTVMAAAAKAFKHPSIRNPVSLVVTRLVILGSGEEGPQVGPSAAQTLRSFCAWQRGLN
  TPEDSDPDHFDTAILFTRQDLCGVSTCDTLGMADVGTVCDPARSCAIVEDDGLQSAFTAA
  HELGHVFNMLHDNSKPCISLNGPLSTSRHVMAPVMAHVDPEEPWSPCSARFITDFLDNGY
  GHCLLDKPEAPLHLPVTFPGKDYDADRQCQLTFGPDSRHCPQLPPPCAALWCSGHLNGHA
  MCQTKHSPWADGTPCGPAQACMGGRCLHMDQLQDFNIPQAGGWGPWGPWGDCSRTCGGGV
  QFSSRDCTRPVPRNGGKYCEGRRTRFRSCNTEDCPTGSALTFREEQCAAYNHRTDLFKSF
  PGPMDWVPRYTGVAPQDQCKLTCQAQALGYYYVLEPRVVDGTPCSPDSSSVCVQGRCIHA
  GCDRIIGSKKKFDKCMVCGGDGSGCSKQSGSFRKFRYGYNNVVTIPAGATHILVRQQGNP
  GHRSIYLALKLPDGSYALNGEYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLAQP
  LTLQVLVAGNPQDTRLRYSFFVPRPTPSTPRPTPQDWLHRRAQILEILRRRPWAGRK
• 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. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site.
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Degradation of the extracellular matrix (R-HSA-1474228)
• BioCyc Pathway: MetaCyc:ENSG00000158859-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1607004-34-1	DMM2N4T	N. A.	N. A.	Patented	[2]
US9206139, 4	DM3NE8J	N. A.	N. A.	Patented	[2]
US9206139, 5	DMB4JS7	N. A.	N. A.	Patented	[2]

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	[1]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-2-(biphenyl-4-sulfonylamino)-propionic acid	DM16JFS	Discovery agent	N.A.	Investigative	[3]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[3]

References

• [1] 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.
• [2] Aggrecanase inhibitors. US9206139.
• [3] Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors. Bioorg Med Chem Lett. 2006 Jan 15;16(2):311-6.