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MedKoo Cat#: 503750 | Name: Riociguat
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Riociguat, also known as BAY 63-2521, is a novel drug that is currently in clinical development by Bayer. It is a stimulator of soluble guanylate cyclase (sGC). At the moment Phase III clinical trials investigate the use of riociguat as a new approach to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of a novel class of sGC stimulators.

Chemical Structure

Riociguat
Riociguat
CAS#625115-55-1

Theoretical Analysis

MedKoo Cat#: 503750

Name: Riociguat

CAS#: 625115-55-1

Chemical Formula: C20H19FN8O2

Exact Mass: 422.1615

Molecular Weight: 422.42

Elemental Analysis: C, 56.87; H, 4.53; F, 4.50; N, 26.53; O, 7.58

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 225.00 Ready to ship
100mg USD 400.00 Ready to ship
200mg USD 700.00 Ready to ship
500mg USD 1,250.00 Ready to ship
1g USD 2,250.00 Ready to ship
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Related CAS #
No Data
Synonym
BAY 63-2521; BAY63-2521; BAY632521; Riociguat; Brand name: Adempas.
IUPAC/Chemical Name
methyl (4,6-diamino-2-(1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-5-yl)(methyl)carbamate
InChi Key
WXXSNCNJFUAIDG-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(OC)N(C1=C(N)N=C(C2=NN(CC3=CC=CC=C3F)C4=NC=CC=C42)N=C1N)C
Appearance
Light yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
         
Biological target:
Riociguat is an oral stimulator of soluble guanylate cyclase (sGC) used in the treatment of pulmonary hypertension.
In vitro activity:
Riociguat was identified as a weak to moderate inhibitor of P-gp (f2-value: 11.7 ± 4.8 μM), BCRP (IC50 = 46.2 ± 20.3 μM), OATP1B1 (IC50 = 34.1 ± 3.15 μM), OATP1B3 (IC50 = 50.3 ± 7.5 μM), CYP2D6 (IC50 = 12.4 ± 0.74 μM), and CYP2C19 (IC50 = 46.1 ± 7.14 μM). Furthermore, it induced mRNA expression of BCRP/ABCG2 (3-fold at 20 μM) and to a lesser extent of CYP3A4 (2.3-fold at 20 μM), UGT1A4, and ABCB11. The only weak inducing properties were confirmed by weak activation of PXR. Reference: Pulm Pharmacol Ther. 2014 Aug;28(2):130-7. https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(14)00032-7
In vivo activity:
Upon chronic hypoxic exposure, Prvs increased significantly from 23.0±0.4 to 29.8±1.9 and 34.8±1.9 mmHg (for control, 21 and 35 days hypoxia, respectively; fig. 6a⇓). No significant changes in Psa were observed (fig. 6b⇓). In the chronic treatment group, BAY 63-2521 was orally applied at a dose of 10 mg·kg−1·day−1 from day 21 to 35. BAY 63-2521 significantly decreased Prvs to 29.0±0.6 mmHg (p<0.05 versus hypoxia at day 35). In order to further investigate haemodynamics in chronic hypoxic mice, a telemetric approach was performed. Continuous telemetric measurement of Prvs in conscious mice under chronic hypoxic exposure revealed a continuous increase in the Prvs curve, which was shouldered around day 5 and followed by a progressive increase thereafter. Oral treatment with BAY 63-2521 at a dose of 10 mg·kg−1·day−1 from day 21 to 35 reduced hypoxia-induced PAH (fig. 7a). During the development of PAH, cardiac frequency increased from 380±30 to 496±14 bpm (fig. 7b⇓). When comparing the pre- and post-treatment values, no significant decrease was noted by chronic BAY 63-2521 application. Reference: Eur Respir J. 2008 Oct;32(4):881-91. http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=18550612
Solvent mg/mL mM
Solubility
DMSO 84.0 198.85
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 422.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Rickert V, Haefeli WE, Weiss J. Pharmacokinetic interaction profile of riociguat, a new soluble guanylate cyclase stimulator, in vitro. Pulm Pharmacol Ther. 2014 Aug;28(2):130-7. doi: 10.1016/j.pupt.2014.02.004. Epub 2014 Mar 21. PMID: 24657506. 2. Reinke Y, Gross S, Eckerle LG, Hertrich I, Busch M, Busch R, Riad A, Rauch BH, Stasch JP, Dörr M, Felix SB. The soluble guanylate cyclase stimulator riociguat and the soluble guanylate cyclase activator cinaciguat exert no direct effects on contractility and relaxation of cardiac myocytes from normal rats. Eur J Pharmacol. 2015 Nov 15;767:1-9. doi: 10.1016/j.ejphar.2015.09.022. Epub 2015 Sep 25. PMID: 26407652. 3. Schermuly RT, Stasch JP, Pullamsetti SS, Middendorff R, Müller D, Schlüter KD, Dingendorf A, Hackemack S, Kolosionek E, Kaulen C, Dumitrascu R, Weissmann N, Mittendorf J, Klepetko W, Seeger W, Ghofrani HA, Grimminger F. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 Oct;32(4):881-91. doi: 10.1183/09031936.00114407. Epub 2008 Jun 11. PMID: 18550612.
In vitro protocol:
1. Rickert V, Haefeli WE, Weiss J. Pharmacokinetic interaction profile of riociguat, a new soluble guanylate cyclase stimulator, in vitro. Pulm Pharmacol Ther. 2014 Aug;28(2):130-7. doi: 10.1016/j.pupt.2014.02.004. Epub 2014 Mar 21. PMID: 24657506. 2. Reinke Y, Gross S, Eckerle LG, Hertrich I, Busch M, Busch R, Riad A, Rauch BH, Stasch JP, Dörr M, Felix SB. The soluble guanylate cyclase stimulator riociguat and the soluble guanylate cyclase activator cinaciguat exert no direct effects on contractility and relaxation of cardiac myocytes from normal rats. Eur J Pharmacol. 2015 Nov 15;767:1-9. doi: 10.1016/j.ejphar.2015.09.022. Epub 2015 Sep 25. PMID: 26407652.
In vivo protocol:
1. Schermuly RT, Stasch JP, Pullamsetti SS, Middendorff R, Müller D, Schlüter KD, Dingendorf A, Hackemack S, Kolosionek E, Kaulen C, Dumitrascu R, Weissmann N, Mittendorf J, Klepetko W, Seeger W, Ghofrani HA, Grimminger F. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 Oct;32(4):881-91. doi: 10.1183/09031936.00114407. Epub 2008 Jun 11. PMID: 18550612.
1: Ghio S, Bonderman D, Felix SB, Ghofrani HA, Michelakis ED, Mitrovic V, Oudiz RJ, Frey R, Roessig L, Semigran MJ. Left ventricular systolic dysfunction associated with pulmonary hypertension riociguat trial (LEPHT): rationale and design. Eur J Heart Fail. 2012 Aug;14(8):946-53. Epub 2012 Jun 20. PubMed PMID: 22719060. 2: Geschka S, Kretschmer A, Sharkovska Y, Evgenov OV, Lawrenz B, Hucke A, Hocher B, Stasch JP. Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats. PLoS One. 2011;6(7):e21853. Epub 2011 Jul 18. PubMed PMID: 21789188; PubMed Central PMCID: PMC3138745. 3: Schermuly RT, Janssen W, Weissmann N, Stasch JP, Grimminger F, Ghofrani HA. Riociguat for the treatment of pulmonary hypertension. Expert Opin Investig Drugs. 2011 Apr;20(4):567-76. Epub 2011 Mar 11. Review. PubMed PMID: 21391889. 4: Mitrovic V, Jovanovic A, Lehinant S. Soluble guanylate cyclase modulators in heart failure. Curr Heart Fail Rep. 2011 Mar;8(1):38-44. Review. PubMed PMID: 21207207. 5: Kim NH. Riociguat: an upcoming therapy in chronic thromboembolic pulmonary hypertension? Eur Respir Rev. 2010 Mar;19(115):68-71. Review. PubMed PMID: 20956169. 6: Frey R, Mück W, Kirschbaum N, Krätzschmar J, Weimann G, Wensing G. Riociguat (BAY 63-2521) and warfarin: a pharmacodynamic and pharmacokinetic interaction study. J Clin Pharmacol. 2011 Jul;51(7):1051-60. Epub 2010 Aug 27. PubMed PMID: 20801938. 7: Sharkovska Y, Kalk P, Lawrenz B, Godes M, Hoffmann LS, Wellkisch K, Geschka S, Relle K, Hocher B, Stasch JP. Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models. J Hypertens. 2010 Aug;28(8):1666-75. PubMed PMID: 20613628. 8: Ghofrani HA, Hoeper MM, Halank M, Meyer FJ, Staehler G, Behr J, Ewert R, Weimann G, Grimminger F. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J. 2010 Oct;36(4):792-9. Epub 2010 Jun 7. PubMed PMID: 20530034. 9: Schenk M. [Pulmonary arterial hypertension--a rare form of pulmonary hypertension]. Dtsch Med Wochenschr. 2010 May;135(21):p21. Epub 2010 May 27. German. PubMed PMID: 20509110. 10: Loukanov T, Geiger R, Agrawal R. Animal models related to congenital heart disease and clinical research in pulmonary hypertension. Cardiology. 2010;116(1):18-25. Epub 2010 Apr 24. PubMed PMID: 20424448.