Details of the Drug

General Information of Drug (ID: DM8DZC1)

• Drug Name: Dyphylline
• Synonyms: Aristophyllin; Asthmolysin; Astmamasit; Astrophyllin; Circain; Circair; Coronal; Coronarin; Corphyllin; Dihydroxypropyltheophylline; Diprofilina; Diprofillin; Diprofillina; Diprofilline; Diprophyllin; Diprophylline; Diprophyllinum; Dipropylline; Droxine; Dyflex; Glyfyllin; Glyphyllin; Glyphylline; Glyphyllinum; Hidroxiteofillina; Hiphyllin; Hyphylline; Iphyllin; Isophyllen; Liactemin; Lufyllin; Neophyl; Neophyllin; Neophylline; Neostenovasan; Neothylline; Neotilina; Neufil; Neutrafil; Neutrafillina; Neutraphyllin; Neutraphylline; Neutroxantina; Propyphyllin; Protheophylline; Purifilin; Silbephyllin; Silbephylline; Solufilin; Solufyllin; Soluphyllin; Synthophylline; Tefilan; Teofen; Tesfen; Theal; Thefylan; Dihydroxypropyl theophylline; Dihydroxypropyl theopylin; Dilor G; Diprofillina [DCIT]; Dyphylline [USAN]; Neophyllin M; Theal ampules; AFI-Phyllin; COR-theophylline; Dihydroxypropyl theopylin (german); Dilor-400; Diphyllin (VAN); Diprofilina [INN-Spanish]; Diprophyllinum [INN-Latin]; Dyphylline (USP); Lufyllin (TN); Neo-Vasophylline; Diprophylline (JAN/INN); Neothylline, Lufyllin, diprophylline,Dyphylline; (+-)-7-(2,3-Dihydroxypropyl)theophylline; (+-)-diprophylline; (+-)-dyphylline; (1,2-Dihydroxy-3-propyl)thiophyllin; 1,3-Dimethyl-7-(2,3-dihydroxypropyl)xanthine; 1H-Purine-2,6-dione, 7-(2,3-dihydroxypropyl)-3,7-dihydro-1,3-dimethyl; 7-(2,3-Dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione; 7-(2,3-Dihydroxypropyl)-1,3-dimethylxanthine; 7-(2,3-Dihydroxypropyl)-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; 7-(2,3-Dihydroxypropyl)theophylline; 7-(2,3-Dioxypropyl)theophylline; 7-(2,3-dihydroxypropyl)-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione; 7-(2,3-dihydroxypropyl)-1,3-dimethylpurine-2,6-dione; 7-(beta,gamma-Dihydroxypropyl)theophylline; 7-(beta.,.gamma.-Dihydroxypropyl)theophylline; 7-DIHYDROXYPROPYLTHEOPHYLLINE; 7-[2,3-Dihydroxypropyl]-theophylline

Indication

Disease Entry	ICD 11	Status	REF
Acute bronchial asthma	CA23	Approved	[1]
Pulmonary emphysema	CA21.Z	Approved	[2]
Asthma	CA23	Investigative	[2]

• Therapeutic Class: Bronchodilator Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 254.24
  Logarithm of the Partition Coefficient (xlogp); -1.8
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Bioavailability: 90% of drug becomes completely available to its intended biological destination(s) [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 4.8 mL/min/kg [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.7 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 235.99054 micromolar/kg/day [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.42 L/kg [4]
• Chemical Identifiers:
  Formula: C10H14N4O4
  IUPAC Name: 7-(2,3-dihydroxypropyl)-1,3-dimethylpurine-2,6-dione
  Canonical SMILES: CN1C2=C(C(=O)N(C1=O)C)N(C=N2)CC(CO)O
  InChI: InChI=1S/C10H14N4O4/c1-12-8-7(9(17)13(2)10(12)18)14(5-11-8)3-6(16)4-15/h5-6,15-16H,3-4H2,1-2H3
  InChIKey: KSCFJBIXMNOVSH-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3182
  ChEBI ID: CHEBI:4728
  CAS Number: 479-18-5
  DrugBank ID: DB00651
  TTD ID: D02PWM
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 4A (PDE4A)	TTZ97H5	PDE4A_HUMAN	Inhibitor	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Acute bronchial asthma
• ICD Disease Classification: CA23

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Phosphodiesterase 4A (PDE4A)	DTT	PDE4A	6.55E-01	1.40E-02	0.04

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dyphylline (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Febuxostat	DMDEXQ0	Moderate	Decreased metabolism of Dyphylline caused by Febuxostat mediated inhibition of non-CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[7]
Probenecid	DMMFWOJ	Minor	Decreased renal excretion of Dyphylline caused by Probenecid.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[8]
Blinatumomab	DMGECIJ	Moderate	Decreased metabolism of Dyphylline caused by Blinatumomab mediated inhibition of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[9]

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: 7070).
• [2] Dyphylline FDA Label
• [3] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [7] Product Information. Uloric (febuxostat). Takeda Pharmaceuticals America, Lincolnshire, IL.
• [8] Acara M, Carr EA Jr, Terry EN "Probenecid inhibition of the renal excretion of dyphyllin in chicken, rat and man." J Pharm Pharmacol 39 (1987): 526-30. [PMID: 2886621]
• [9] Product Information. Blincyto (blinatumomab). Amgen USA, Thousand Oaks, CA.