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| Targets |
F3288-0031 targets the norepinephrine transporter (NET), a protein responsible for the reuptake of norepinephrine from the synaptic cleft back into the presynaptic neuron. It binds to the lumen of NET, a site distinct from the orthosteric binding pocket, and stabilizes an internal opening conformation of the transporter. This allosteric mechanism leads to preferential inhibition of NET over the serotonin transporter (SERT), giving it a distinct pharmacological profile.
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| ln Vitro |
In vitro, F3288-0031 acts as a norepinephrine transporter (NET) allosteric inhibitor. It demonstrates a 73.5% inhibition rate of NET at a concentration of 20 uM. It exhibits preferential inhibitory activity for both NET and the serotonin transporter (SERT), with a pIC50 (the negative log of the IC50) of 5.9. Notably, no detectable off-target functional activity was observed in screening assays, indicating high selectivity for these monoamine transporters.
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| ln Vivo |
F3288-0031 (3-50 mg/kg, intraperitoneal injection, single dose) showed antidepressant-like activity in C57BL/6J mice, with no effect on motor activity [1].
No direct in vivo efficacy data are provided in the search results. As an allosteric NET inhibitor, it is hypothesized that F3288-0031 would have in vivo effects similar to other NET inhibitors. By blocking norepinephrine reuptake, it would increase its synaptic concentration and duration, potentially leading to an antidepressant-like effect. In vivo efficacy would be tested in standard preclinical models of depression (e.g., the forced swim test) and anxiety. |
| Enzyme Assay |
NET binding and inhibition can be assessed using radioligand binding. Membranes from cells expressing recombinant human NET are incubated with a high-affinity radioligand, such as [3H]-nisoxetine, in the presence of various concentrations of F3288-0031. Allosteric binding can be determined by its effect on the dissociation rate of the radioligand. [3H]-Norepinephrine uptake is measured in NET-expressing cells. Cells are pre-incubated with various concentrations of F3288-0031, followed by addition of [3H]-norepinephrine. After a fixed incubation, uptake is terminated by rapid washing, and cell-associated radioactivity is counted. The IC50 is the concentration that inhibits 50% of [3H]-norepinephrine uptake.
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| Cell Assay |
To confirm activity in a neuronal context, SH-SY5Y human neuroblastoma cells (which express NET) are seeded in 24-well plates. They are pre-incubated with various concentrations of F3288-0031 (e.g., 0.1-100 microM). Following a wash step, the cells are incubated with a fluorescent norepinephrine analog, such as ASP+ (4-(4-(dimethylamino)phenyl)-1-methylpyridinium). The uptake of the fluorescent substrate is then quantified using a fluorescence plate reader or a flow cytometer. A reduction in cellular fluorescence indicates that F3288-0031 is effectively blocking NET function in a cellular environment.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6J mice (6-8 weeks)[1]
Doses: 3, 10, 30, 50 mg/kg Route of Administration: i.p., once Experimental Results: Demonstrated a dose-dependent decrease in immobility time in the forced swim test (FST), with significant reductions at 30 and 50 mg/kg. Did not significantly alter spontaneous locomotor activity at 3, 10, 30 mg/kg. In vivo activity for a NET inhibitor can be evaluated in the FST using male Swiss-Webster or C57BL/6 mice (n=10/group). Mice are pretreated with F3288-0031 or vehicle at a specific time before the test. In the 6-min forced swim test, the total immobility time during the last 4 min is recorded. A significant reduction in immobility time compared to the vehicle control group indicates an antidepressant-like effect. Desipramine (a known NET inhibitor) is used as a positive control. |
| ADME/Pharmacokinetics |
No specific pharmacokinetic data are available for F3288-0031. For a CNS-active drug, good blood-brain barrier penetration and a favorable brain-plasma ratio are critical. A NET inhibitor would be expected to have a half-life suitable for once- or twice-daily dosing. Preclinical ADME (absorption, distribution, metabolism, excretion) studies would be required to fully characterize its PK profile.
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| Toxicity/Toxicokinetics |
No specific toxicology data are available. As an allosteric inhibitor of a CNS target, F3288-0031 would require extensive preclinical safety testing, including hERG testing for cardiac safety, assessment of potential for drug-drug interactions via CYP450 profiling, and repeated-dose toxicity studies in rodents. Standard safety precautions for handling research chemicals apply: use PPE, work in a fume hood.
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| References | |
| Additional Infomation |
F3288-0031 (CAS# 926493-93-8) is a research-grade allosteric norepinephrine transporter (NET) inhibitor. It is a valuable tool for dissecting the role of NET in neuropsychiatric disorders, including depression and anxiety, and for developing new allosteric modulators of monoamine transporters. It is not an FDA-approved drug. For research use only.
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| Molecular Formula |
C24H32N2O3
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| Molecular Weight |
396.52
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| CAS # |
926493-93-8
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| Appearance |
Typically exists as solids 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5219 mL | 12.6097 mL | 25.2194 mL | |
| 5 mM | 0.5044 mL | 2.5219 mL | 5.0439 mL | |
| 10 mM | 0.2522 mL | 1.2610 mL | 2.5219 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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