Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH9WF6)

• DTT Name: Dibasic-processing enzyme (Furin)
• Synonyms: Paired basic amino acid residuecleaving enzyme; Paired basic amino acid residue-cleaving enzyme; PCSK3; PACE; FUR; Dibasicprocessing enzyme
• Gene Name: FURIN
• DTT Type: Preclinical target; [1]
• BioChemical Class: Peptidase
• UniProt ID: FURIN_HUMAN
• TTD ID: T68706
• EC Number: EC 3.4.21.75
• Sequence:
  MELRPWLLWVVAATGTLVLLAADAQGQKVFTNTWAVRIPGGPAVANSVARKHGFLNLGQI
  FGDYYHFWHRGVTKRSLSPHRPRHSRLQREPQVQWLEQQVAKRRTKRDVYQEPTDPKFPQ
  QWYLSGVTQRDLNVKAAWAQGYTGHGIVVSILDDGIEKNHPDLAGNYDPGASFDVNDQDP
  DPQPRYTQMNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAVEARSL
  GLNPNHIHIYSASWGPEDDGKTVDGPARLAEEAFFRGVSQGRGGLGSIFVWASGNGGREH
  DSCNCDGYTNSIYTLSISSATQFGNVPWYSEACSSTLATTYSSGNQNEKQIVTTDLRQKC
  TESHTGTSASAPLAAGIIALTLEANKNLTWRDMQHLVVQTSKPAHLNANDWATNGVGRKV
  SHSYGYGLLDAGAMVALAQNWTTVAPQRKCIIDILTEPKDIGKRLEVRKTVTACLGEPNH
  ITRLEHAQARLTLSYNRRGDLAIHLVSPMGTRSTLLAARPHDYSADGFNDWAFMTTHSWD
  EDPSGEWVLEIENTSEANNYGTLTKFTLVLYGTAPEGLPVPPESSGCKTLTSSQACVVCE
  EGFSLHQKSCVQHCPPGFAPQVLDTHYSTENDVETIRASVCAPCHASCATCQGPALTDCL
  SCPSHASLDPVEQTCSRQSQSSRESPPQQQPPRLPPEVEAGQRLRAGLLPSHLPEVVAGL
  SCAFIVLVFVTVFLVLQLRSGFSFRGVKVYTMDRGLISYKGLPPEAWQEECPSDSEEDEG
  RGERTAFIKDQSAL
• Function: Mediates processing of TGFB1, an essential step in TGF-beta-1 activation. Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif.
• KEGG Pathway: Viral life cycle - HIV-1 (hsa03250)
• Reactome Pathway:
  Collagen degradation (R-HSA-1442490)
  Elastic fibre formation (R-HSA-1566948)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  NGF processing (R-HSA-167060)
  Synthesis and processing of ENV and VPU (R-HSA-171286)
  Signaling by PDGF (R-HSA-186797)
  Pre-NOTCH Processing in Golgi (R-HSA-1912420)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  Uptake and function of anthrax toxins (R-HSA-5210891)
  Formation of the cornified envelope (R-HSA-6809371)
  Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889)
  CD163 mediating an anti-inflammatory response (R-HSA-9662834)
  Potential therapeutics for SARS (R-HSA-9679191)
  Attachment and Entry (R-HSA-9694614)
  Amyloid fiber formation (R-HSA-977225)
  Signaling by NODAL (R-HSA-1181150)

Molecular Interaction Atlas (MIA) of This DTT

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9266828, B	DMYUDCE	N. A.	N. A.	Patented	[2]
US9266828, C	DMQEL1W	N. A.	N. A.	Patented	[2]
US9266828, E	DMYUL2X	N. A.	N. A.	Patented	[2]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DecRVKRCMK	DMAUILH	Coronavirus infection	1D92	Preclinical	[3]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
furin inhibitor peptide	DM78NOM	Discovery agent	N.A.	Investigative	[4]
MI-1148	DMCN91V	Discovery agent	N.A.	Investigative	[5]
peptide 18	DMIDP1R	Discovery agent	N.A.	Investigative	[1]

References

• [1] Design, synthesis, and structure-activity relationship studies of a potent PACE4 inhibitor. J Med Chem. 2014 Jan 9;57(1):98-109.
• [2] Inhibitors of Furin and other pro-protein convertases. US9266828.
• [3] Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage. Viruses. 2019 Oct 31;11(11):1011.
• [4] Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. J Biol Chem. 2007 Jul 20;282(29):20847-53.
• [5] Novel Furin Inhibitors with Potent Anti-infectious Activity. ChemMedChem. 2015 Jul;10(7):1218-31.