Riociguat

Summary

Riociguat (CHEMBL2107834) is an approved small-molecule soluble guanylate cyclase activator (ATC C02KX05); indicated across 13 conditions including pulmonary arterial hypertension and hypertensive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02KX05
• Indications: 13 conditions
• Clinical trials: 29
• Chemistry: 422.4 Da · C20H19FN8O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2107834
Name	Riociguat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11304743
ChEBI	CHEBI:76018
ATC	C02KX05
Molecular formula	C20H19FN8O2
Molecular weight	422.4
InChIKey	WXXSNCNJFUAIDG-UHFFFAOYSA-N

SMILES: CN(C1=C(N=C(N=C1N)C2=NN(C3=C2C=CC=N3)CC4=CC=CC=C4F)N)C(=O)OC

IUPAC name: methyl N-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[5,4-b]pyridin-3-yl]pyrimidin-5-yl]-N-methylcarbamate

ChEBI definition: A carbamate ester that is the methyl ester of {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamic acid. It is used for treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension

Pharmacological roles (ChEBI): soluble guanylate cyclase activator, antihypertensive agent.

Also known as: Adempas, Riociguat, RIOCIGUAT, RiociguatÊ, RiociguatÂ, riociguat

Patent coverage: 579 distinct patent families (1,431 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 1,195 (84%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
	Guanylyl cyclase, α1β1	Activation
	Guanylyl cyclase, α2β1	Activation

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Voltage-gated inwardly rectifying potassium channel KCNH2, Adenosine receptor A3.

Bioactivity

ChEMBL activities: 1 potent at pChembl ≥ 5 of 2 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
KCNH2	5.3	AC50	5000	nM	CHEMBL_ACT_25117613

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

13 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
pulmonary arterial hypertension	4	MONDO:0015924	EFO:0001361
hypertensive disorder	4	MONDO:0005044	EFO:0000537
pulmonary hypertension	4	MONDO:0005149	MONDO:0005149
systemic sclerosis	2	MONDO:0005100	EFO:0000717
Raynaud disease	2	MONDO:0008364	EFO:1001145
scleroderma	2	MONDO:0019340	EFO:1001993
ulcer disease	2	MONDO:0043839	MONDO:0043839
coronary artery disorder	2	MONDO:0005010	EFO:0001645
cystic fibrosis	2	MONDO:0009061	MONDO:0009061
sickle cell disease	2	MONDO:0011382	MONDO:0011382
HIV infectious disease	1	MONDO:0005109	EFO:0000764

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 29.

Phase distribution

Phase	Trials
PHASE2	10
PHASE4	6
PHASE1	6
PHASE3	4
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05825417	PHASE4	RECRUITING	Pulmonary Hypertension: Intensification and Personalisation of Combination Rx
NCT06715280	PHASE4	RECRUITING	Switching of Sildenafil to Riociguat in CTEPH Patients
NCT02024386	PHASE4	COMPLETED	Efficacy Study of Riociguat and Its Effects on Exercise Performance and Pulmonary Artery Pressure at High Altitude
NCT02625558	PHASE4	UNKNOWN	Riociguat for Sarcoidosis Associated Pulmonary Hypertension
NCT03809156	PHASE4	UNKNOWN	Upfront Combination Pulmonary Arterial Hypertension Therapy
NCT04954742	PHASE4	TERMINATED	Effects of Riociguat on RIght VEntricular Size and Function in PAH and CTEPH
NCT04062565	PHASE3	RECRUITING	Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH
NCT05140525	PHASE3	RECRUITING	Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
NCT06922240	PHASE3	RECRUITING	Riociguat-Discontinue Effects on Right HEART in CTEPH (RED-HEART)
NCT00863681	PHASE3	COMPLETED	BAY63-2521:Long-term Extension Study in Patients With Pulmonary Arterial Hypertension
NCT01165931	PHASE2	WITHDRAWN	Coronary Vasomotor Response After Riociguat Exposure
NCT01172756	PHASE2	TERMINATED	A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Diastolic Dysfunction
NCT02633397	PHASE2	COMPLETED	A Multi-Center Study of Riociguat in Patients With Sickle Cell Diseases
NCT02744339	PHASE2	COMPLETED	Pharmacodynamic Effects of Riociguat in Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction
NCT02915835	PHASE2	COMPLETED	Riociguat in Scleroderma Associated Digital Ulcers
NCT03273257	PHASE2	TERMINATED	Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy (PEA Bridging Study)
NCT03409588	PHASE2	COMPLETED	Treatment of Exercise-Induced Pulmonary Vascular Dysfunction After Pulmonary Thromboendarterectomy or Balloon Pulmonary Angioplasty
NCT04600492	PHASE2	UNKNOWN	THERAPY-HYBRID-BPA Trial
NCT05339087	PHASE2	TERMINATED	Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH
NCT05762146	PHASE2	UNKNOWN	Networked Drug REpurposing for Mechanism-based neuroPrOtection in Acute Ischaemic STROKE
NCT01489488	PHASE1	COMPLETED	Relative Bioavailability and Food Effect Study
NCT02159326	PHASE1	COMPLETED	Microgynon Riociguat Drug Interaction Study in Healthy Postmenopausal Women
NCT03389321	PHASE1	COMPLETED	Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics
NCT04211272	PHASE1	COMPLETED	A 2-part Study to Investigate the Effect of Macitentan in Healthy Male Participants
NCT04776499	PHASE1	COMPLETED	Possible Effects of Propylthiouracil, Riociguat and Perphenazine on Circulation of Healthy Volunteers
NCT06180096	PHASE1	COMPLETED	Bioequivalence Study of Riociguat 2.5 mg Film Coated Tablets and Adempas (Riociguat) 2.5 mg Film Coated Tablets
NCT02634203	Not specified	COMPLETED	Riociguat Versus Balloon Pulmonary Angioplasty in Non-operable Chronic thromboEmbolic Pulmonary Hypertension
NCT03074539	Not specified	COMPLETED	Sleep-Disordered Breathing in Chronic Thromboembolic Pulmonary Hypertension
NCT05582811	Not specified	COMPLETED	Effect of Riocigaut on Cerebral Vasodilation and Headache Induction in Healthy Volunteers

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).