| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(R)-BAY-747 targets soluble guanylate cyclase (sGC), a key signal-transducing enzyme that is the receptor for nitric oxide (NO). It acts as a direct sGC stimulator, binding to a site on the enzyme that is distinct from the NO binding site. By stabilizing the active conformation of sGC, it greatly enhances the enzyme's sensitivity to low levels of NO, leading to increased production of the second messenger cyclic GMP (cGMP), which mediates vasodilation, inhibition of platelet aggregation, and other protective effects.
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| ln Vitro |
BAY-747 is a highly potent sGC stimulator in vitro. It demonstrates potent enzyme activation in cell-free assays. As a member of a new generation of sGC stimulators, it shows a very low peak-to-trough ratio, indicating a more consistent, long-acting pharmacodynamic effect compared to earlier compounds, potentially reducing the risk of hypotension. Its brain-penetrant property was confirmed in pharmacokinetic studies.
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| ln Vivo |
In vivo, BAY-747 is an orally active sGC stimulator with long-acting pharmacodynamic effects. It reverses L-NAME induced memory impairments and enhances cognition in rats, as assessed in the object location task (OLT). These results highlight its potential as a treatment for resistant hypertension, where its consistent hemodynamic effect is beneficial. Its oral availability and long half-life support once-daily dosing.
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| Enzyme Assay |
The activity of sGC stimulators is measured in an in vitro enzyme assay using purified human sGC. The enzyme is incubated with a substrate, GTP, and varying concentrations of BAY-747. The production of cGMP is quantified by a homogeneous time-resolved fluorescence (HTRF) assay or ELISA. The EC50 is the concentration that produces 50% of the maximal enzyme activation. The ability to stimulate in the presence of sub-saturating NO concentrations is a key measure of a stimulator's potency.
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| Cell Assay |
The functional activity of sGC stimulators can be measured in cells expressing sGC. Human embryonic kidney (HEK293) cells or rat aortic smooth muscle cells are pre-incubated with varying concentrations of BAY-747 (0.1-1000 nM). After the addition of a sub-saturating concentration of an NO donor (e.g., DEA-NONOate), the cells are lysed, and the concentration of cGMP is quantified by ELISA. The EC50 is the concentration causing a 50% increase in cGMP accumulation.
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| Animal Protocol |
Cognitive effects of (R)-BAY-747 can be evaluated in the object location task (OLT) using male Wistar rats. Rats are treated with L-NAME (a nitric oxide synthase inhibitor) to induce memory impairment. They are then administered (R)-BAY-747 (e.g., 3, 10, 30 mg/kg, PO) or a positive control (e.g., sildenafil) before the OLT. The test measures the rodents' natural preference for exploring a displaced object. A preference for the object in a novel location indicates intact spatial memory. For hypertension, efficacy is measured by telemetry in conscious, freely moving hypertensive rats.
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| ADME/Pharmacokinetics |
Soluble guanylate cyclase (sGC) stimulators are generally well absorbed orally, with BAY-747 demonstrating high oral bioavailability. The brain-penetrant property suggests that the drug can cross the blood-brain barrier. Preclinical PK studies in rats would show dose-proportional increases in exposure (Cmax and AUC). BAY-747 was designed to have a long pharmacodynamic half-life to maintain a very low peak-to-trough ratio, aiming for consistent 24-hour blood pressure control.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available for (R)-BAY-747. As a highly potent vasodilator, the primary potential adverse effect is symptomatic hypotension (excessive lowering of blood pressure), especially at higher doses. Preclinical safety assessments would include a safety pharmacology core battery (including CNS, respiratory, and cardiovascular systems) and repeat-dose toxicity studies in two species. Given its brain-penetrant nature, CNS side effects would also be carefully evaluated.
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| References | |
| Additional Infomation |
(R)-BAY-747 is a research-stage compound that has advanced into non-clinical development, but there is no indication it has yet progressed to clinical trials. BAY-747 is designed as a potent, oral sGC stimulator for resistant hypertension, with the potential to provide a safe and effective treatment. It has not received FDA approval.
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| Molecular Formula |
C22H26F2N4O2
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|---|---|
| Molecular Weight |
416.46
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| Related CAS # |
BAY-747; 1609342-18-8
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| Appearance |
White to off-white solid powder
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| Synonyms |
(R)-BAY 1165747
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4012 mL | 12.0060 mL | 24.0119 mL | |
| 5 mM | 0.4802 mL | 2.4012 mL | 4.8024 mL | |
| 10 mM | 0.2401 mL | 1.2006 mL | 2.4012 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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