Details of the Drug

General Information of Drug (ID: DMVZ0ND)

• Drug Name: PMID27998201-Compound-5

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Patented	[1]
Cirrhosis	DB93	Patented	[1]
Gastrointestinal disease	DE2Z	Patented	[1]
Multiple sclerosis	8A40	Patented	[1]
Psoriasis vulgaris	EA90	Patented	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 479.6
  Topological Polar Surface Area (xlogp); 4.3
  Rotatable Bond Count (rotbonds); 12
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C23H27F2N3O2S2
  IUPAC Name: (2R)-N-(1-cyanocyclopropyl)-3-(cyclopropylmethylsulfanyl)-2-[[(2S)-1,1-difluoro-1-(4-methylsulfanylphenoxy)pent-3-yn-2-yl]amino]propanamide
  Canonical SMILES: CC#C[C@@H](C(OC1=CC=C(C=C1)SC)(F)F)N[C@@H](CSCC2CC2)C(=O)NC3(CC3)C#N
  InChI: InChI=1S/C23H27F2N3O2S2/c1-3-4-20(23(24,25)30-17-7-9-18(31-2)10-8-17)27-19(14-32-13-16-5-6-16)21(29)28-22(15-26)11-12-22/h7-10,16,19-20,27H,5-6,11-14H2,1-2H3,(H,28,29)/t19-,20-/m0/s1
  InChIKey: UKRDTRXIEUADJU-PMACEKPBSA-N
• Cross-matching ID:
  PubChem CID: 46202117
  TTD ID: D05OIU

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cathepsin B (CTSB)	TTF2LRI	CATB_HUMAN	Inhibitor	[1]
Cathepsin F (CTSF)	TTJOKD1	CATF_HUMAN	Inhibitor	[1]
Cathepsin K (CTSK)	TTDZN01	CATK_HUMAN	Inhibitor	[1]
Cathepsin L (CTSL)	TT36ETB	CATL1_HUMAN	Inhibitor	[1]
Cathepsin S (CTSS)	TTUMQVO	CATS_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Chronic obstructive pulmonary disease
• ICD Disease Classification: CA22

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cathepsin K (CTSK)	DTT	CTSK	2.85E-01	-1.14	-2.61

References

• [1] Cathepsin B and L inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2017 Jun;27(6):643-656.
• [2] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [3] From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor. Eur J Pharm Biopharm. 2013 Apr;83(3):436-48.
• [4] Discovery and parallel synthesis of a new class of cathepsin K inhibitors. Bioorg Med Chem Lett. 2001 Nov 19;11(22):2951-4.
• [5] An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.
• [6] Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6610-5.
• [7] Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional se... J Med Chem. 2005 Dec 1;48(24):7535-43.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] 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: 2353).
• [10] Clinical pipeline report, company report or official report of ViroBay.
• [11] Clinical pipeline report, company report or official report of ViroBay.
• [12] Selective nitrile inhibitors to modulate the proteolytic synergism of cathepsins S and F. J Med Chem. 2012 Jun 28;55(12):5982-6.
• [13] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [14] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.