Details of the Drug Combination

General Information of Drug Combination (ID: DCF422P)

Drug Combination Name
Roflumilast Theophylline
Indication
Disease Entry Status REF
COPD Phase 3 [1]
Component Drugs Roflumilast   DMPGHY8 Theophylline   DMRJFN9
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Roflumilast
Disease Entry ICD 11 Status REF
Asthma CA23 Approved [2]
Type-2 diabetes 5A11 Phase 1 [3]
Chronic obstructive pulmonary disease CA22 Withdrawn from market [2]
Atopic dermatitis EA80 Discontinued in Phase 2 [2]
Roflumilast Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phosphodiesterase 4 (PDE4) TTV5CGO NOUNIPROTAC Modulator [6]
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Roflumilast Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [7]
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Roflumilast Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B) OT4217NK PDE8B_HUMAN Decreases Activity [8]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [9]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [9]
3',5'-cyclic-AMP phosphodiesterase 4A (PDE4A) OTMUUZLF PDE4A_HUMAN Decreases Activity [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [9]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [9]
3',5'-cyclic-AMP phosphodiesterase 4B (PDE4B) OTOA8WU2 PDE4B_HUMAN Decreases Activity [8]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [9]
3',5'-cyclic-AMP phosphodiesterase 4C (PDE4C) OTI8VMHZ PDE4C_HUMAN Decreases Activity [8]
3',5'-cyclic-AMP phosphodiesterase 4D (PDE4D) OT1RWFV0 PDE4D_HUMAN Decreases Activity [8]
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (PDE3B) OT1GI1TE PDE3B_HUMAN Decreases Activity [8]
High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (PDE7A) OTVDV4IT PDE7A_HUMAN Decreases Activity [8]
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (PDE3A) OTKUW1WT PDE3A_HUMAN Decreases Activity [8]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [9]
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⏷ Show the Full List of 15 DOT(s)
Indication(s) of Theophylline
Disease Entry ICD 11 Status REF
Bronchitis CA20 Approved [4]
Chronic obstructive pulmonary disease CA22 Approved [5]
Lung cancer 2C25.0 Approved [4]
Non-small-cell lung cancer 2C25.Y Approved [4]
Pulmonary disease 1B10-1F85 Approved [4]
Pulmonary emphysema CA21.Z Approved [4]
Severe asthma CA23 Approved [4]
Asthma CA23 Investigative [4]
Theophylline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine receptor (ADOR) TTSLI08 NOUNIPROTAC Antagonist [10]
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Theophylline Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [11]
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Theophylline Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [13]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [14]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [12]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [15]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [16]
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⏷ Show the Full List of 6 DME(s)
Theophylline Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases ADR [17]
Renin (REN) OT52GZR2 RENI_HUMAN Increases ADR [17]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases ADR [17]
Cyclic GMP-AMP phosphodiesterase SMPDL3A (SMPDL3A) OTQDYH8E ASM3A_HUMAN Increases ADR [17]
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References

1 ClinicalTrials.gov (NCT02340520) Enhancement of Corticosteroid Efficacy in COPD
2 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: 6962).
3 ClinicalTrials.gov (NCT01664624) Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes. U.S. National Institutes of Health.
4 Theophylline FDA Label
5 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: 413).
6 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
7 Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2011 Apr;51(4):586-93.
8 Dynamic activation of cystic fibrosis transmembrane conductance regulator by type 3 and type 4D phosphodiesterase inhibitors. J Pharmacol Exp Ther. 2005 Aug;314(2):846-54. doi: 10.1124/jpet.105.083519. Epub 2005 May 18.
9 Roflumilast protects from cisplatin-induced testicular toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line. Role of NF-B-p65, cAMP/PKA and Nrf2/HO-1, NQO1 signaling. Food Chem Toxicol. 2021 May;151:112133. doi: 10.1016/j.fct.2021.112133. Epub 2021 Mar 20.
10 Emerging adenosine receptor agonists. Expert Opin Emerg Drugs. 2007 Sep;12(3):479-92.
11 Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver. Drug Metab Dispos. 2005 May;33(5):619-22.
12 Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem Pharmacol. 1995 Jul 17;50(2):205-11.
13 Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers. Basic Clin Pharmacol Toxicol. 2013 Apr;112(4):257-63.
14 Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7.
15 Construction and assessment of models of CYP2E1: predictions of metabolism from docking, molecular dynamics, and density functional theoretical calculations. J Med Chem. 2003 Apr 24;46(9):1645-60.
16 Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22.
17 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.