Details of the Drug

General Information of Drug (ID: DM3C8GQ)

• Drug Name: PF-489791
• Synonyms: UNII-2S27T3DSZ3; PF-489791; PF-00489791; 853003-48-2; 2S27T3DSZ3; PF-489,791; ZUHZNKJIJDAJFD-UHFFFAOYSA-N; UK-489,791; SCHEMBL331279; SCHEMBL8042129; GTPL8377; DB11736; SB16722; 1H-Pyrazolo(4,3-d)pyrimidine-3-carboxamide, 1-(2-ethoxyethyl)-5-(ethylmethylamino)-7-((4-methyl-2-pyridinyl)amino)-N-(methylsulfonyl); n-[1-(2-ethoxyethyl)-5-(n-ethyl-n-methylamino)-7-(4-methylpyridin-2-yl-amino)-1h-pyrazolo[4,3-d]pyrimidine-3-carbonyl]methanesulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Phase 2	[1]
Raynaud disease	BD42.0	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 476.6
  Topological Polar Surface Area (xlogp); 1.6
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 10
• Chemical Identifiers:
  Formula: C20H28N8O4S
  IUPAC Name: 1-(2-ethoxyethyl)-5-[ethyl(methyl)amino]-7-[(4-methylpyridin-2-yl)amino]-N-methylsulfonylpyrazolo[4,3-d]pyrimidine-3-carboxamide
  Canonical SMILES: CCN(C)C1=NC2=C(C(=N1)NC3=NC=CC(=C3)C)N(N=C2C(=O)NS(=O)(=O)C)CCOCC
  InChI: InChI=1S/C20H28N8O4S/c1-6-27(4)20-23-15-16(19(29)26-33(5,30)31)25-28(10-11-32-7-2)17(15)18(24-20)22-14-12-13(3)8-9-21-14/h8-9,12H,6-7,10-11H2,1-5H3,(H,26,29)(H,21,22,23,24)
  InChIKey: ZUHZNKJIJDAJFD-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11465695
  CAS Number: 853003-48-2
  DrugBank ID: DB11736
  TTD ID: D0M9FQ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Inhibitor	[2]

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
Phosphodiesterase 5A (PDE5A)	DTT	PDE5A	1.60E-01	-0.25	-0.99

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025495)
• [2] Highlights of the society for medicinesresearch symposium held december 10th 2009 at the national heart and lung institute, London, UK. Drugs of the Future 2010, 35(4): 349-358.
• [3] Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
• [4] Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical d... Asian J Androl. 2009 Jul;11(4):435-42.
• [5] The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. J Am Coll Cardiol. 2002 Dec 4;40(11):2006-12.
• [6] Anti-platelet therapy: phosphodiesterase inhibitors.Br J Clin Pharmacol.2011 Oct;72(4):634-46.
• [7] Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium. J Pharmacol Exp Ther. 2009 Sep;330(3):884-91.
• [10] Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J Nat Prod. 2008 Sep;71(9):1513-7.
• [11] Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res. 2000 Jul 1;60(13):3338-42.
• [12] Highly potent and selective chiral inhibitors of PDE5: an illustration of Pfeiffer's rule. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6033-6.