Details of the Drug

General Information of Drug (ID: DMGZPX6)

• Drug Name: PI-88
• Synonyms: CHEMBL603733

Indication

Disease Entry	ICD 11	Status	REF
Hepatocellular carcinoma	2C12.02	Phase 3	[1]
Prostate cancer	2C82.0	Phase 2	[1]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight; 2516.5
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 30
  Hydrogen Bond Donor Count; 0
  Hydrogen Bond Acceptor Count; 77
• Chemical Identifiers:
  Formula: C30H35Na15O77PS16-3
  IUPAC Name: pentadecasodium;[(2R,3R,4S,5S,6R)-6-[(2R,3S,4S,5R,6R)-2-[(2R,3S,4S,5R,6R)-2-[(2R,3R,4S,5S,6R)-3,5-disulfonatooxy-2-(sulfonatooxymethyl)-6-[(2R,3S,4R,5R,6R)-2,4,5-trisulfonatooxy-6-(sulfonatooxymethyl)oxan-3-yl]oxyoxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl]oxy-3,4,5-trisulfonatooxyoxan-2-yl]methyl phosphate
  Canonical SMILES: C([C@@H]1[C@H]([C@@H]([C@@H]([C@H](O1)O[C@H]2[C@@H]([C@H](O[C@@H]([C@H]2OS(=O)(=O)[O-])O[C@H]3[C@@H]([C@H](O[C@@H]([C@H]3OS(=O)(=O)[O-])O[C@H]4[C@@H]([C@H](O[C@@H]([C@H]4OS(=O)(=O)[O-])O[C@H]5[C@H]([C@@H]([C@H](O[C@@H]5OS(=O)(=O)[O-])COS(=O)(=O)[O-])OS(=O)(=O)[O-])OS(=O)(=O)[O-])COS(=O)(=O)[O-])OS(=O)(=O)[O-])COS(=O)(=O)[O-])OS(=O)(=O)[O-])COS(=O)(=O)[O-])OS(=O)(=O)[O-])OS(=O)(=O)[O-])OS(=O)(=O)[O-])OS(=O)(=O)[O-])OP(=O)([O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
  InChI: InChI=1S/C30H53O77PS16.15Na/c31-108(32,33)82-1-6-14(99-116(55,56)57)20(102-119(64,65)66)25(106-123(76,77)78)29(87-6)94-17-12(97-114(49,50)51)8(3-84-110(37,38)39)89-27(23(17)104-121(70,71)72)92-16-11(96-113(46,47)48)7(2-83-109(34,35)36)88-26(22(16)103-120(67,68)69)93-18-13(98-115(52,53)54)9(4-85-111(40,41)42)90-28(24(18)105-122(73,74)75)95-21-19(101-118(61,62)63)15(100-117(58,59)60)10(5-86-112(43,44)45)91-30(21)107-124(79,80)81;;;;;;;;;;;;;;;/h6-30H,1-5H2,(H2,31,32,33)(H,34,35,36)(H,37,38,39)(H,40,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)(H,79,80,81);;;;;;;;;;;;;;;/q;15*+1/p-18/t6-,7-,8-,9-,10-,11-,12-,13-,14-,15-,16+,17+,18+,19+,20+,21+,22+,23+,24+,25+,26-,27-,28-,29-,30-;;;;;;;;;;;;;;;/m1.............../s1
  InChIKey: FIYNUMVQYZZZCH-JSZMYKOGSA-A
• Cross-matching ID:
  PubChem CID: 46233427
  DrugBank ID: DB05808
  TTD ID: D04ZJG

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 3 (FLT-4)	TTDCBX5	VGFR3_HUMAN	Modulator	[2]

Molecular Expression Atlas of This Drug

• ICD Disease Classification: 02 Neoplasm
• Disease Class: ICD-11: 2C82 Prostate cancer
• The Studied Tissue: Prostate
• The Studied Disease: Prostate cancer [ICD-11:2C82]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 3 (FLT-4)	DTT	FLT4	8.36E-03	0.45	0.97

References

• [1] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [2] Company report (Medigen)
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [4] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [5] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [6] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [7] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [8] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
• [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: 1814).
• [10] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [11] Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
• [12] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.