Details of the Drug

General Information of Drug (ID: DMXBLMP)

Drug Name
Riociguat
Synonyms
Riociguat; 625115-55-1; Adempas; Riociguat (BAY 63-2521); BAY 63-2521; riociguatum; UNII-RU3FE2Y4XI; RU3FE2Y4XI; CHEBI:76018; Methyl (4,6-diamino-2-(1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)(methyl)carbamate; Methyl N-(4,6-diamino-2-{1-((2-fluorophenyl)methyl)-1H-pyrazolo(3,4-b)pyridin-3-yl}pyrimidin-5-yl)-N-methylcarbamate; N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methylcarbamic acid methyl ester
Indication
Disease Entry ICD 11 Status REF
Chronic thromboembolic pulmonary hypertension N.A. Approved [1]
Pulmonary arterial hypertension BB01.0 Approved [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 422.4
Logarithm of the Partition Coefficient (xlogp) 1.6
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.74 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 12 hours [3]
Vd
The volume of distribution (Vd) of drug is 30 L []
Chemical Identifiers
Formula
C20H19FN8O2
IUPAC Name
methyl N-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]-N-methylcarbamate
Canonical SMILES
CN(C1=C(N=C(N=C1N)C2=NN(C3=C2C=CC=N3)CC4=CC=CC=C4F)N)C(=O)OC
InChI
InChI=1S/C20H19FN8O2/c1-28(20(30)31-2)15-16(22)25-18(26-17(15)23)14-12-7-5-9-24-19(12)29(27-14)10-11-6-3-4-8-13(11)21/h3-9H,10H2,1-2H3,(H4,22,23,25,26)
InChIKey
WXXSNCNJFUAIDG-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11304743
ChEBI ID
CHEBI:76018
CAS Number
625115-55-1
DrugBank ID
DB08931
TTD ID
D04UKC
VARIDT ID
DR00080
INTEDE ID
DR1427
ACDINA ID
D00597
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
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
Soluble guanylyl cyclase (GUCY2D) TTWNFC2 GUC2D_HUMAN Modulator [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [7]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [7]
Cytochrome P450 2J2 (CYP2J2) DERSX5P CP2J2_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Potassium channel subfamily K member 3 (KCNK3) OTWMAV6G KCNK3_HUMAN Drug Response [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Riociguat (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Riociguat caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [9]
Arn-509 DMT81LZ Moderate Increased metabolism of Riociguat caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [9]
Gilteritinib DMTI0ZO Moderate Decreased clearance of Riociguat due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [10]
Ag-221 DMS0ZBI Moderate Decreased clearance of Riociguat due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [10]
Tucatinib DMBESUA Moderate Decreased metabolism of Riociguat caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [10]
SODIUM CITRATE DMHPD2Y Moderate Decreased absorption of Riociguat due to altered gastric pH caused by SODIUM CITRATE. Discovery agent [N.A.] [9]
Cobicistat DM6L4H2 Major Decreased clearance of Riociguat due to the transporter inhibition by Cobicistat. Human immunodeficiency virus disease [1C60-1C62] [10]
Ceritinib DMB920Z Moderate Decreased metabolism of Riociguat caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [10]
PF-06463922 DMKM7EW Moderate Increased metabolism of Riociguat caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [9]
Capmatinib DMYCXKL Moderate Decreased clearance of Riociguat due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [10]
Idelalisib DM602WT Moderate Decreased metabolism of Riociguat caused by Idelalisib mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [10]
Lasmiditan DMXLVDT Moderate Decreased clearance of Riociguat due to the transporter inhibition by Lasmiditan. Migraine [8A80] [11]
Tedizolid DMG2SKR Moderate Decreased clearance of Riociguat due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [12]
Elagolix DMB2C0E Moderate Increased metabolism of Riociguat caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [9]
⏷ Show the Full List of 14 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Riociguat 2 mg tablet 2 mg Oral Tablet Oral
Riociguat 2.5 mg tablet 2.5 mg Oral Tablet Oral
Riociguat 1 mg tablet 1 mg Oral Tablet Oral
Riociguat 1.5 mg tablet 1.5 mg Oral Tablet Oral
Riociguat 0.5 mg tablet 0.5 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Riociguat FDA Label
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: 5257).
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
5 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
6 Pharmacokinetic interaction profile of riociguat, a new soluble guanylate cyclase stimulator, initro. Pulm Pharmacol Ther. 2014 Aug;28(2):130-7.
7 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.
8 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.
9 Product Information. Adempas (riociguat). Bayer Pharmaceutical Inc, West Haven, CT.
10 Cerner Multum, Inc. "Australian Product Information.".
11 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
12 Cerner Multum, Inc. "UK Summary of Product Characteristics.".