| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
sGC[2]
Riociguat-13C,d6 targets the same enzyme as its non-deuterated parent: soluble guanylate cyclase (sGC). The compound stimulates sGC in a concentration-dependent manner (0.1 to 100 microM) through an NO-independent but haem-dependent mechanism, producing a two-fold to 73-fold effect. The isotopic labeling does not alter the mechanism of action. |
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1]. Riocigua acts through a haem-dependent but NO-independent mechanism to stimulate the recombinant sGC concentration dependently from 0.1 to 100 μM, with an effect ranging from two to 73 times[1]. Riociguat has no direct impact on the contractility and relaxation of cardiac myocytes, however it impairs platelet activity in washed platelets but not in whole blood[2].
In vitro, Riociguat-13C,d6 is used as a tracer for quantitation during drug development. The parent compound, Riociguat, stimulates recombinant sGC concentration dependently from 0.1 to 100 microM with a two-fold to 73-fold effect by an NO-independent but haem-dependent mechanism. Riociguat inhibits platelet function in washed platelets but not in whole blood, and exerts no direct effects on contractility and relaxation of cardiac myocytes. |
| ln Vivo |
In prolonged therapy of hypoxic mice and MCT-injected rats, rivicuat (10 mg/kg/d, po) partially reverses the pulmonary arterial hypertension, the hypertrophy of the right heart, and the structural remodeling of the lung vasculature[3].
In vivo, Riociguat (10 mg/kg/d, p.o.) partially reverses pulmonary arterial hypertension, right heart hypertrophy, and structural remodelling of lung vasculature in chronic treatment of hypoxic mice and MCT-injected rats. The deuterated version is an analytical standard and is not administered for therapeutic purposes. |
| Enzyme Assay |
Riociguat-13C,d6 is not used in an enzyme binding assay; it is an internal standard for LC-MS/MS. A fixed concentration (e.g., 10-50 ng/mL) of the labeled internal standard is added to biological samples (e.g., plasma, tissue homogenates). Samples are extracted by protein precipitation or solid-phase extraction and analyzed on an LC-MS/MS system. Riociguat is detected in positive ion mode using specific MRM transitions (e.g., m/z 323 → 294). The labeled internal standard has a mass shift corresponding to +13 and +6 Da (total +19). The peak area ratio is used for quantification.
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| Cell Assay |
Riociguat-13C,d6 is not used in typical cell-based assays. The parent compound, Riociguat, is used to study sGC activation in cellular models. Human umbilical vein endothelial cells (HUVECs) or pulmonary artery smooth muscle cells (PASMCs) are seeded in 96-well plates. Cells are treated with Riociguat (0.1-100 microM) for 30-60 min. cGMP levels are measured by ELISA. The deuterated version is used as an internal standard for quantifying Riociguat uptake in these cells.
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| Animal Protocol |
Riociguat-13C,d6 is used as an internal standard for PK studies of Riociguat. A standard protocol: male Sprague-Dawley rats (200-250 g) are administered a single oral dose of Riociguat (1-10 mg/kg) in 0.5% methylcellulose. Blood samples are collected at pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h post-dose. Plasma is separated. A fixed concentration of Riociguat-13C,d6 is added to each sample. Samples are extracted and analyzed by LC-MS/MS. PK parameters are calculated using non-compartmental analysis.
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| ADME/Pharmacokinetics |
Riociguat-13C,d6 has a molecular weight of 429.45 and the molecular formula C19¹3CH13D6FN8O2. The powder should be stored at -20degC for up to 3 years or at 4degC for up to 2 years. In solvent, it is stable for 6 months at -80degC or 1 month at -20degC. The compound is soluble in DMF and DMSO (≥10 mg/mL).
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| Toxicity/Toxicokinetics |
The non-deuterated parent, Riociguat, is generally well-tolerated in clinical settings. Common adverse effects include hypotension, headache, dizziness, and dyspepsia. The deuterated version is used in trace amounts as an analytical standard and does not pose additional safety risks beyond standard chemical handling. Standard safety precautions for handling pharmaceutical compounds should be followed.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-223.
[2]. Schermuly RT, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 Oct;32(4):881-91. [3]. Schermuly RT, et al. Riociguat for the treatment of pulmonary hypertension.Expert Opin Investig Drugs. 2011 Apr;20(4):567-76. |
| Additional Infomation |
Riociguat-13C,d6 is a research-grade stable isotope-labeled compound and is not approved for clinical use. It is used as an internal standard for the quantification of Riociguat, an oral sGC stimulator for pulmonary hypertension. This product is for research use only and not for human therapeutic applications. Store as a powder at -20degC or 4degC.
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| Molecular Formula |
C1913CH13D6FN8O2
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|---|---|
| Related CAS # |
Riociguat;625115-55-1
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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