riociguat
Trade name: adempas
Approved
Oct 8, 2013
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. — NCATS
Clinical trial activity
56 trials · 32 clinical orgs · 3 marketing orgs
Earliest trial started Jan 1, 2007 (NCT00454558)
Timeline
2000s
2010s
2020s
- Mar 30, 2022
Teva — Marketing Organization
- Sep 1, 2022
MSN Laboratories — Marketing Organization
Indications
Studied for
- Altitude Sickness · Phase 4
- Anemia, Sickle Cell · Phase 2
- Angioplasty, Balloon · Phase 4
- Connective Tissue · Phase 2
- Coronary Artery Disease · Phase 2
- Cystic Fibrosis · Phase 2
- Drug Interactions · Phase 1
- Familial Primary Pulmonary Hypertension · Phase 2
- General Surgery · Phase 2
- Healthy Volunteers · Phase 1
- Heart Failure, Diastolic · Phase 2
- HIV Infections · Phase 1
- Ischemic Stroke · Phase 2
- Lung Diseases · Phase 2
- Pharmacology, Clinical · Phase 1
- Pneumonia · Phase 2
- Pulmonary Arterial Hypertension · Phase 4
- Pulmonary Disease, Chronic Obstructive · Phase 1
- Raynaud Disease · Phase 2
- Sarcoidosis · Phase 4
- Scleroderma, Systemic · Phase 2
- Thromboembolism · Phase 2
- Ulcer · Phase 2
- Ventricular Dysfunction, Left · Phase 2
Mechanism of action
- Soluble guanylate cyclasePOSITIVE ALLOSTERIC MODULATOR
Soluble guanylate cyclase positive allosteric modulator
Riociguat has a dual mode of action. It sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding and it also directly stimulates sGC via a different binding site, independently of NO. Recent studies have suggested that sCG stimulators bind to an allosteric nucleotide-binding site in the catalytic domains of sCG. The exact molecular mechanism of sCG stimulation remains a matter of debate.
Approval history
- approvedOct 8, 2013
Chemistry & pharmacology
SMILES
COC(=O)N(C)C1=C(N)N=C(N=C1N)C2=NN(CC3=CC=CC=C3F)C4=C2C=CC=N4- Mol. weight
- 422.4157 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral
- Availability
- Prescription Only
Oral
Yes
Parenteral
No
Topical
No
Sources
- WikipediaRiociguat ↗
- NCATSRU3FE2Y4XI ↗
- ChEMBLCHEMBL2107834 ↗
Also known as
- adempas
- adempas
- adempas
- adempas
- adempas
- adempas
- adempas
- adempas
- bay 63-2521
- bay 63-2521
- bay-63-2521
- methyl n-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]-1h-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-n-methyl-carbaminate
- methyl n-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]-1h-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-n-methyl-carbaminate
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguat
- riociguatum
- riociguatum
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT06922240 | Phase 3 | Mar 21, 2025 | Capital Medical University, Peking University |
| NCT06715280 | Phase 4 | Jul 25, 2024 | Chinese University of Hong Kong |
| NCT05825417 | Phase 4 | Jun 14, 2023 | Newcastle University, Sheffield Hallam University, University of Cambridge, University of Glasgow |
| NCT05750446 | N/A | Apr 1, 2023 | University of Copenhagen |
| NCT06180096 | Phase 1 | Mar 7, 2023 | Humanis Saglık Anonim Sirketi |
| NCT05582811 | N/A | Oct 11, 2022 | University of Copenhagen |
| NCT05762146 | Phase 2 | Sep 5, 2022 | Maastricht University |
| NCT05339087 | Phase 2 | Jul 31, 2022 | Merck, University of Heidelberg |
| NCT05140525 | Phase 3 | Jan 31, 2022 | Actelion, Duke University |
| NCT04954742 | Phase 4 | Sep 30, 2021 | Merck, University of Heidelberg |
| NCT04776499 | Phase 1 | Mar 18, 2021 | European Commission, Maastricht University, University of Heidelberg |
| NCT04600492 | Phase 2 | Oct 16, 2020 | Bayer, National Hospital Organisation Nagoya Medical Centre, National Hospital Organization Okayama Medical Center |
| NCT04211272 | Phase 1 | Jan 13, 2020 | Actelion |
| NCT04062565 | Phase 3 | Mar 25, 2019 | University of Arizona |
| NCT03409588 | Phase 2 | Oct 31, 2018 | Bayer, University of Colorado, Denver |
| NCT03273257 | Phase 2 | Aug 17, 2018 | International CTEPH Association, Papworth Hospital NHS Foundation Trust |
| NCT03362047 | Phase 2 | Mar 1, 2018 | Justus Liebig University Giessen, Philipps University of Marburg |
| NCT03389321 | Phase 1 | Jan 9, 2018 | Actelion |
| NCT02633397 | Phase 2 | Apr 11, 2017 | University of Pittsburgh |
| NCT03074539 | N/A | Feb 1, 2017 | Medical University of Vienna |
Organizations
Research & Development (32)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Bayer | For profit | 35 | 30 | 5 | 2007 |
| Merck | For profit | 4 | 0 | 3 | 2014 |
| Actelion | For profit | 3 | 2 | 2 | 2018 |
| University of Heidelberg | Academic/Hospital | 3 | 2 | 3 | 2021 |
| Duke University | Academic/Hospital | 2 | 2 | 2 | 2014 |
| Maastricht University | Academic/Hospital | 2 | 2 | 2 | 2021 |
| University of Copenhagen | Academic/Hospital | 2 | 2 | 1 | 2022 |
| Capital Medical University | Academic/Hospital | 1 | 1 | 1 | 2025 |
| Chinese University of Hong Kong | Academic/Hospital | 1 | 1 | 1 | 2024 |
| European Commission | Government | 1 | 0 | 1 | 2021 |
| Humanis Saglık Anonim Sirketi | Academic/Hospital | 1 | 1 | 1 | 2023 |
| Inova Health System | Academic/Hospital | 1 | 0 | 1 | 2015 |
| International CTEPH Association | Academic/Hospital | 1 | 1 | 1 | 2018 |
| Justus Liebig University Giessen | Academic/Hospital | 1 | 1 | 1 | 2018 |
| Medical University of Vienna | Academic/Hospital | 1 | 1 | 1 | 2017 |
| National Hospital Organisation Nagoya Medical Centre | Academic/Hospital | 1 | 0 | 1 | 2020 |
| National Hospital Organization Okayama Medical Center | Academic/Hospital | 1 | 1 | 1 | 2020 |
| Newcastle University | Academic/Hospital | 1 | 0 | 1 | 2023 |
| Papworth Hospital NHS Foundation Trust | Academic/Hospital | 1 | 0 | 1 | 2018 |
| Peking University | Academic/Hospital | 1 | 0 | 1 | 2025 |
Marketing (3)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Bayer | For profit | NDA | Oct 8, 2013 |
| MSN Laboratories | For profit | MKTG | Sep 1, 2022 |
| Teva | For profit | MKTG | Mar 30, 2022 |