| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Phosphodiesterase 9A (PDE9A) - no specific IC50/Ki provided in this paper; the compound is described as a selective PDE9A inhibitor. [1]
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|---|---|
| ln Vitro |
In SH-SY5Y cells, BAY 73-6691 (50, 100, 150, 200 μg/ml) dose-dependently alleviated Aβ25-35 (20 μM)-induced loss of cell viability as measured by MTT assay. [1]
In SH-SY5Y cells, BAY 73-6691 dose-dependently attenuated Aβ25-35-induced cell apoptosis evaluated by Annexin V-FITC/PI double staining and flow cytometry. [1] In SH-SY5Y cells, BAY 73-6691 dose-dependently decreased the elevated malondialdehyde (MDA) level and increased the decreased activities of total antioxidant capability (T-AOC), glutathione peroxidase (GSH-PX) and catalase (CAT) induced by Aβ25-35, indicating attenuation of oxidative stress. At 200 μg/ml, BAY 73-6691 almost completely neutralized Aβ25-35-induced oxidative damage. [1] |
| ln Vivo |
In ICR mice with intracerebroventricular injection of Aβ25-35 (9 nmol/mouse on day 0), intraperitoneal administration of BAY 73-6691 (0.3, 1, 3 mg/kg once daily on days 1-10) dose-dependently improved spatial memory deficits in the Morris water maze task, as shown by reduced escape latency and increased dwell time in the target quadrant without affecting swimming speed. BAY 73-6691 at 3 mg/kg almost completely abolished the prolonged escape latency on days 9-10. [1]
In the hippocampus of Aβ25-35-injected mice, BAY 73-6691 (3 mg/kg) significantly decreased the elevated MDA level and increased the decreased activities of T-AOC, GSH-PX and CAT, indicating attenuation of hippocampal oxidative stress. [1] BAY 73-6691 (3 mg/kg) reduced the number of apoptotic cells in the hippocampus (TUNEL staining) and increased hippocampal levels of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) as measured by ELISA and Western blotting, respectively, in Aβ25-35-injected mice. [1] |
| Cell Assay |
SH-SY5Y human neuroblastoma cells were cultured in DMEM/Ham's F12 with 10% FBS, 2 mM L-glutamine, antibiotics, at 37°C, 5% CO2. Cells were plated in 96-well plates at 1×10^5 cells/well and treated with freshly prepared Aβ25-35 (20 μM) with or without BAY 73-6691 (50, 100, 150, 200 μg/ml) for 24, 48, and 72 h. Cell viability was assessed by MTT assay: 20 μl of MTT solution (5 mg/ml) added per well for 4 h, then DMSO added, absorbance read at 550 nm. [1]
Cell apoptosis was evaluated by Annexin V-FITC/PI double staining. Cells (1.0×10^6/ml) were collected, incubated with Annexin V-FITC in binding buffer for 15 min in dark, then PI added for 5 min, and analyzed by flow cytometry within 1 h. [1] Oxidative stress in SH-SY5Y cells: MDA level measured by thiobarbituric acid reaction (TBAR) method; T-AOC measured by ferric reducing antioxidant power (FRAP) assay; GSH-PX activity measured by NADPH oxidation at 340 nm; CAT activity measured by decomposition of H2O2 at 520 nm. All kits were used according to manufacturer's protocols. [1] |
| Animal Protocol |
Male ICR mice (25-30 g) were used. Alzheimer's disease model was induced by intracerebroventricular (i.c.v.) injection of Aβ25-35 (9 nmol in 3 μl per mouse) on day 0 under chloral hydrate anesthesia (400 mg/kg i.p.). Sham mice received vehicle. BAY 73-6691 was dissolved and administered intraperitoneally (i.p.) once daily at 7:30 AM on days 1-10 at doses of 0.3, 1, and 3 mg/kg. Control groups received vehicle. [1]
Morris water maze (MWM) task: pool diameter 90 cm, water temperature 20°C, submerged platform. Mice were trained from day 1 to day 4 post-Aβ injection (4 trials/day, 90 s max). MWM was performed on days 5-10. Swimming speed was assessed without platform. Latency to find platform and dwell time in target quadrant were recorded. [1] For biochemical assays, mice were sacrificed on day 10, hippocampus was removed, homogenized in ice-cold PBS (10:1 vol/wt), and MDA, T-AOC, GSH-PX, CAT measured as in cell assays. [1] For TUNEL staining, mice were perfused with PBS then 4% paraformaldehyde, hippocampus processed, and apoptotic cells counted (cells/mm) in subgranular zone. [1] For Western blotting, hippocampal proteins (20 μg) were separated by 10% SDS-PAGE, transferred to nitrocellulose, and probed with anti-GAP-43 antibody (1:300). β-actin as internal control. [1] For BDNF ELISA, commercial kit used, absorbance read at 450 nm. [1] |
| References | |
| Additional Infomation |
BAY 73-6691 is a selective phosphodiesterase 9 (PDE9) inhibitor with high affinity for cGMP. The compound has been shown to potentiate and prolong long-term potentiation (LTP) in rat hippocampus and improve memory in rodent models. This study demonstrates that BAY 73-6691 exerts neuroprotective effects against Aβ25-35-induced oxidative stress, spatial memory deficits, and hippocampal neuron damage, possibly via regulation of cGMP/NO signaling and upregulation of BDNF and GAP-43. The compound is a promising candidate for Alzheimer's disease therapy. [1]
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| Molecular Formula |
C15H12CLF3N4O
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|---|---|
| Molecular Weight |
356.730192184448
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| Exact Mass |
356.065
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| CAS # |
794568-90-4
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| Related CAS # |
BAY 73-6691;794568-92-6;(S)-BAY 73-6691;794568-91-5
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| PubChem CID |
135495130
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| Appearance |
White to off-white solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
527
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(N2N=CC3C(=O)N=C(NC2=3)CC(C)C(F)(F)F)=C(C=CC=C1)Cl
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| InChi Key |
FFPXPXOAFQCNBS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H12ClF3N4O/c1-8(15(17,18)19)6-12-21-13-9(14(24)22-12)7-20-23(13)11-5-3-2-4-10(11)16/h2-5,7-8H,6H2,1H3,(H,21,22,24)
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| Chemical Name |
1-(2-chlorophenyl)-6-(3,3,3-trifluoro-2-methylpropyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one
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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) |
DMSO : ≥ 100 mg/mL (~280.32 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (14.02 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 5 mg/mL (14.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: 5 mg/mL (14.02 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8032 mL | 14.0162 mL | 28.0324 mL | |
| 5 mM | 0.5606 mL | 2.8032 mL | 5.6065 mL | |
| 10 mM | 0.2803 mL | 1.4016 mL | 2.8032 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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