Details of the Drug Combination

General Information of Drug Combination (ID: DCJ769Y)

Drug Combination Name
Macitentan Riociguat
Indication
Disease Entry Status REF
CTEPH Phase 3 [1]
Component Drugs Macitentan   DMP79A1 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 Macitentan
Disease Entry ICD 11 Status REF
Cardiovascular disease BA00-BE2Z Approved [2]
Macitentan Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Endothelin A receptor (EDNRA) TTKRD0G EDNRA_HUMAN Modulator [5]
Endothelin B receptor (EDNRB) TT3ZTGU EDNRB_HUMAN Modulator [5]
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Macitentan Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [6]
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Macitentan Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Decreases Expression [7]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [7]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Expression [7]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Expression [7]
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Indication(s) of Riociguat
Disease Entry ICD 11 Status REF
Chronic thromboembolic pulmonary hypertension N.A. Approved [3]
Pulmonary arterial hypertension BB01.0 Approved [4]
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 [5]
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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 [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
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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 [10]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [10]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [10]
Cytochrome P450 2J2 (CYP2J2) DERSX5P CP2J2_HUMAN Metabolism [10]
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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 [11]
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References

1 ClinicalTrials.gov (NCT05140525) Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
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: 7352).
3 Riociguat FDA Label
4 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).
5 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
6 Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects. Clin Pharmacokinet. 2013 Aug;52(8):685-92.
7 From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062.
8 Pharmacokinetic interaction profile of riociguat, a new soluble guanylate cyclase stimulator, initro. Pulm Pharmacol Ther. 2014 Aug;28(2):130-7.
9 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
10 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.
11 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.