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BAY-747 (BAY 1165747) 1609342-18-8

BAY-747 (BAY 1165747) 1609342-18-8

CAS No.: 1609342-18-8

BAY-747 (BAY 1165747) is an orally bioactive and brain-penetrating soluble guanylyl cyclase (sGC) stimulator. BAY-747 re
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BAY-747 (BAY 1165747) is an orally bioactive and brain-penetrating soluble guanylyl cyclase (sGC) stimulator. BAY-747 reverses L-NAME-induced memory impairment and enhances cognition in rats. BAY-747 also reduces blood pressure in conscious normotensive and spontaneously hypertensive rats (SHR). BAY-747 improves skeletal muscle function associated with Duchenne muscular dystrophy (DMD) in the mdx/mTRG2 mouse model.

Physicochemical Properties


CAS # 1609342-18-8
Appearance Typically exists as solid at room temperature
HS Tariff Code 2934.99.9001
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)

Biological Activity


Targets Soluble guanylate cyclase (sGC)[1]
ln Vitro Combining WS with BAY-747 (100 nM) improves AMPA receptor kinetics in an in vitro harvest-like cLTP model [1].
ln Vivo During the study period, BAY-747 showed a brain-to-plasma ratio of 0.6 ± 2.0, indicating a comparatively high brain penetration of 60%[1]. Short-term memory impairment caused by L-NAME is lessened by BAY-747 (0.03-1.0 mg/kg, 2 mL/kg; oral; 30 min before T1 in 24-hour OLT), which improves long-term memory acquisition. The hippocampal GluA1-containing AMPAR dynamics are unaffected by BAY-747[1]. In rats receiving the l-NAME Body weight transgenic model, BAY-747 (0.003-0.3 mg/kg; oral; single dose) lowers blood pressure and (3 mg/kg; oral; once day for 35 days) raises renin[2]. In male mdx/mTRG2 mice, BAY-747 (150 mg/kg chow; oral; 16 weeks) improves skeletal muscle function by increasing grip strength and running speed[3].
Cell Assay Western Blot Analysis[1]
Cell Types: ex vivo acquisition-like cLTP model
Tested Concentrations: 100 nM
Incubation Duration:
Experimental Results: Increased the phosphorylation levels of S845 on GluA1.
Animal Protocol Animal/Disease Models: Rat object location task (OLT) model[1]
Doses: 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg
Route of Administration: PO; 30 min before T1 in a 24 h interval OLT
Experimental Results: Resulted Dramatically higher long-term memory performance at 0.03, 0.1, 0.3 and 1.0 mg/kg dose, 30 min before T1. Attenuated L-NAME induced short-term memory impairments at 0.3 mg /kg and 1 mg/kg. Did not enhance GluA1 trafficking at 1 mg/kg 24 h after treatment.

Animal/Disease Models: Anesthetized, conscious spontaneously hypertensive and conscious normotensive rats[2]
Doses: 0 mg/kg, 0.003 mg/kg, 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, and 0.3 mg/kg
Route of Administration: IV; single dose
Experimental Results: Produced a dose-dependent and long-lasting decrease in blood pressure in rats.

Animal/Disease Models: l-NAME -Treated Renin Transgenic Rats[2]
Doses: 0.3 mg/kg, 3 mg/kg
Route of Administration: PO; one time/day for 35 days; l-NAME treatment: 30 mg/kg, po, for 6 days
Experimental Results: Resulted a significant weight gain among rats. Led to a dose-depend
References

[1]. The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms. Sci Rep. 2022 Mar 4;12(1):3589.

[2]. New Generation of sGC Stimulators: Discovery of Imidazo[1,2-a]pyridine Carboxamide BAY 1165747 (BAY-747), a Long-Acting Soluble Guanylate Cyclase Stimulator for the Treatment of Resistant Hypertension. J Med Chem. 2023 Apr 11.

[3]. Assessing the Use of the sGC Stimulator BAY-747, as a Potential Treatment for Duchenne Muscular Dystrophy. Int J Mol Sci. 2021 Jul 27;22(15):8016.


Solubility Data


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
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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).
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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300:Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)