General Information of Drug Combination (ID: DC523Z8)

Drug Combination Name
Sildenafil Riociguat
Indication
Disease Entry Status REF
Pulmonary Hypertension Phase 1 [1]
Component Drugs Sildenafil   DM4YDAJ Riociguat   DMXBLMP
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 Sildenafil
Disease Entry ICD 11 Status REF
Alveolar capillary dysplasia with misalignment of pulmonary veins N.A. Approved [2]
Erectile dysfunction HA01.1 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Respiratory failure CB41 Investigative [2]
Sildenafil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN phosphodiesterase type 5 (PDE5) TTRYFSB PDE5A_HUMAN Inhibitor [7]
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Sildenafil Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3) OTA6HYBA GBB3_HUMAN Increases Response [8]
Angiotensin-converting enzyme (ACE) OTDF1964 ACE_HUMAN Increases Response [9]
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Indication(s) of Riociguat
Disease Entry ICD 11 Status REF
Chronic thromboembolic pulmonary hypertension N.A. Approved [5]
Pulmonary arterial hypertension BB01.0 Approved [6]
Riociguat Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Soluble guanylyl cyclase (GUCY2D) TTWNFC2 GUC2D_HUMAN Modulator [10]
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Riociguat Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [12]
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Riociguat Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [13]
Cytochrome P450 2J2 (CYP2J2) DERSX5P CP2J2_HUMAN Metabolism [13]
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Riociguat Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium channel subfamily K member 3 (KCNK3) OTWMAV6G KCNK3_HUMAN Decreases Response To Substance [14]
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References

1 ClinicalTrials.gov (NCT01179334) Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters.
2 Sildenafil FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 206401.
4 ClinicalTrials.gov (NCT04304313) A Pilot Study of Sildenafil in COVID-19. U.S. National Institutes of Health.
5 Riociguat FDA Label
6 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: 5257).
7 Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol. 2005 Feb;79(3):1966-9. doi: 10.1128/JVI.79.3.1966-1969.2005.
8 Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study. J Urol. 2003 Mar;169(3):1048-51. doi: 10.1097/01.ju.0000058369.72348.ba.
9 ACE gene I/D and NOS3 G894T polymorphisms and response to sildenafil in men with erectile dysfunction. Urology. 2003 Jul;62(1):152-7. doi: 10.1016/s0090-4295(03)00137-7.
10 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
11 Pharmacokinetic interaction profile of riociguat, a new soluble guanylate cyclase stimulator, initro. Pulm Pharmacol Ther. 2014 Aug;28(2):130-7.
12 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
13 Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58.
14 Characterization and regulation of wild-type and mutant TASK-1 two pore domain potassium channels indicated in pulmonary arterial hypertension. J Physiol. 2019 Feb;597(4):1087-1101. doi: 10.1113/JP277275. Epub 2018 Nov 24.