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Details

Stereochemistry ACHIRAL
Molecular Formula C20H19FN8O2
Molecular Weight 422.4157
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RIOCIGUAT

SMILES

COC(=O)N(C)C1=C(N)N=C(N=C1N)C2=NN(CC3=C(F)C=CC=C3)C4=C2C=CC=N4

InChI

InChIKey=WXXSNCNJFUAIDG-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description

Riociguat is a potent, oral stimulator of soluble guanylate cyclase (sGC). It is the first member of a novel class of compounds, being developed by Bayer as an investigational, oral treatment to target a key molecular mechanism underlying pulmonary hypertension (PH). Riociguat demonstrated robust clinical efficacy in two separate PH indications: chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension(PAH). Riociguat works in two ways: it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding and directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation. Through this unique way of working, riociguat decreases blood pressure within the pulmonary arteries that take blood from the heart to the lungs, reducing pressure on the heart leading to improved patient outcomes.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ADEMPAS
Primary
ADEMPAS

Cmax

ValueDoseCo-administeredAnalytePopulation
29.7 μg/L
1 mg single, oral
RIOCIGUAT plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
158 μg × h/L
1 mg single, oral
RIOCIGUAT plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.67 h
1 mg single, oral
RIOCIGUAT plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
RIOCIGUAT plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended starting dosage is 1 mg taken 3 times a day. For patients who may not tolerate the hypotensive effect of the drug, consider a starting dose of 0.5 mg taken three times a day. If systolic blood pressure remains greater than 95 mmHg and the patient has no signs or symptoms of hypotension, up-titrate the dose by 0.5 mg taken three times a day. Dose increases should be no sooner than 2 weeks apart. The dose can be increased to the highest tolerated dosage, up to a maximum of 2.5 mg taken three times a day. If at any time, the patient has symptoms of hypotension, decrease the dosage by 0.5 mg taken three times a day.
Route of Administration: Oral
In Vitro Use Guide
Human fetal airway smooth muscle (fASM) cells were derived from 18-20 weeks PCA fetuses. Hyperoxia effects were inhibited in the presence of riociguat, a sGC stimulator (50mg/ml, 24 h each).