Details of the Drug

General Information of Drug (ID: DMEK4TJ)

• Drug Name: PI-103
• Synonyms: PI-103; 371935-74-9; PI103; 3-(4-morpholinopyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol; UNII-YQX02F616F; PI 103; PIK-103; Phenol, 3-[4-(4-morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]-; YQX02F616F; CHEBI:90524; AK163162; 3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol; 3-(4-Morpholin-4-Ylpyrido[3',2':4,5]furo[3,2-D]pyrimidin-2-Yl)phenol; Phenol, 3-(4-(4-morpholinyl)pyrido(3',2':4,5)furo(3,2-d)pyrimidin-2-yl)-; 3-(4-(4-Morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol

Indication

Disease Entry	ICD 11	Status	REF
Haematological malignancy	2B33.Y	Investigative	[1]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 348.4
  Logarithm of the Partition Coefficient (xlogp); 2.7
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C19H16N4O3
  IUPAC Name: 3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol
  Canonical SMILES: C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O
  InChI: InChI=1S/C19H16N4O3/c24-13-4-1-3-12(11-13)17-21-15-14-5-2-6-20-19(14)26-16(15)18(22-17)23-7-9-25-10-8-23/h1-6,11,24H,7-10H2
  InChIKey: TUVCWJQQGGETHL-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 9884685
  ChEBI ID: CHEMBL573339
  CAS Number: 371935-74-9
  UNII: YQX02F616F
  DrugBank ID: DB17046
  TTD ID: D0W8XH
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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[3]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Gene/Protein Processing	[4]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Post-Translational Modifications	[5]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[6]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Haematological malignancy
• ICD Disease Classification: 2B33.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase gamma (PIK3CG)	DTT	PIK3CG	1.98E-01	-0.05	-0.55

References

• [1] 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. (Ligand id: 5701).
• [2] The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
• [3] PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells. PLoS One. 2012;7(12):e52898. doi: 10.1371/journal.pone.0052898. Epub 2012 Dec 31.
• [4] The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer. 2010 Apr 1;126(7):1549-61. doi: 10.1002/ijc.24926.
• [5] GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1 (HIF-1) pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. doi: 10.1210/jc.2011-1426. Epub 2011 Oct 12.
• [6] PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res. 2010 Dec;30(12):4951-8.