| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Tesofensine targets the monoamine transporters: dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). It inhibits the reuptake of dopamine (DA) with an IC50 of 6.5 nM, norepinephrine (NE) with an IC50 of 1.7 nM, and serotonin (5-HT) with an IC50 of 11 nM. This triple reuptake inhibition increases the synaptic concentrations of these three key neurotransmitters, which is believed to contribute to its appetite-suppressing and weight-reducing effects.
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| ln Vitro |
Tesofensine demonstrates potent inhibition of neurotransmitter reuptake in vitro. The compound inhibits dopamine reuptake with an IC50 of 6.5 nM, norepinephrine reuptake with an IC50 of 1.7 nM, and serotonin reuptake with an IC50 of 11 nM. These values indicate that Tesofensine is most potent at inhibiting norepinephrine reuptake, followed by dopamine and then serotonin. The compound's ability to simultaneously inhibit all three monoamine transporters distinguishes it from selective reuptake inhibitors.
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| ln Vivo |
In DIO rats, tesofensine (subcutaneous injection, single dose, 0.1-3 mg/kg) can cause hypophagia. Over the course of a 12-hour nocturnal observation period, DIO rats' food intake was significantly and dose-dependently decreased by a single dose of Tesofensine (0.1-3 mg/kg, sc). When tesofensine (2.0 mg/kg, subcutaneous injection) was administered daily for 16 days, there was a notable reduction in weight after 4 days when compared to the vehicle-treated controls [3].
Tesofensine exhibits potent in vivo activity in diet-induced obesity (DIO) rat models. A single subcutaneous dose of 0.1-3 mg/kg induces hypophagia and robustly inhibits food intake over a 12-hour nocturnal observation period in a dose-dependent manner. The ED50 for inhibition of total food intake is estimated to be 1.3 mg/kg. Chronic daily administration of Tesofensine (2.0 mg/kg, s.c.) over 16 days triggers a significant reduction in body weight after 4 days, with an average relative decrease of 8.6±1.4% over the entire treatment period. |
| Enzyme Assay |
In vitro binding assays for Tesofensine are typically conducted using membrane preparations from cells expressing human recombinant dopamine, norepinephrine, or serotonin transporters. Radiolabeled ligands such as [³H]WIN 35,428 for DAT, [³H]nisoxetine for NET, or [³H]paroxetine for SERT are used. Membrane aliquots are incubated with the radioligand and varying concentrations of Tesofensine at room temperature for 60-120 minutes. Non-specific binding is determined in the presence of excess unlabeled competitor. Bound radioactivity is collected by filtration onto glass fiber filters and quantified by scintillation counting. IC50 values are calculated from displacement curves.
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| Cell Assay |
For in vitro cell-based functional reuptake inhibition assays, cells stably expressing human DAT, NET, or SERT are seeded in 96-well plates. Cells are pre-incubated with Tesofensine at various concentrations (typically 0.01-1000 nM) for 15-30 minutes. Radiolabeled neurotransmitters ([³H]dopamine, [³H]norepinephrine, or [³H]serotonin) are then added, and uptake is allowed to proceed for a defined period (e.g., 5-10 minutes) at 37°C. Uptake is terminated by rapid washing with ice-cold assay buffer. Cells are lysed, and accumulated radioactivity is measured by scintillation counting. IC50 values for inhibition of neurotransmitter uptake are calculated from concentration-response curves.
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| Animal Protocol |
Animal/Disease Models: Diet-induced obesity (DIO) rats [3]
Doses: 0.1-3 mg/kg Route of Administration: subcutaneousadministration (sc); single dose (acute treatment) Experimental Results: The threshold dose for inhibiting total food intake is 1.0 mg/kg. The ED50 for inhibition of total food intake in DIO rats is estimated to be 1.3 mg/kg. Animal/Disease Models: Diet-induced obesity (DIO) rats [3] Doses: 2.0 mg/kg Route of Administration: Daily subcutaneousadministration for more than 16 days (long-term treatment) Experimental Results: Average body weight after tisofensin treatment The relative decrease in DIO rats during the entire treatment period was 8.6±1.4%. The relative weight loss for tisofensin was 13.8 ± 1.4% compared to vehicle control. Tesofensine is administered subcutaneously in in vivo studies. For acute studies, a single dose of 0.1-3 mg/kg is given, and food intake is monitored over 12 hours during the nocturnal period. For chronic studies, Tesofensine (2.0 mg/kg) is administered subcutaneously daily for 16 days. Body weight is measured daily throughout the treatment period. Diet-induced obesity (DIO) rats are used as the animal model, which are maintained on a high-fat diet to induce obesity prior to treatment. Food intake is measured by weighing food hoppers before and after the observation period. |
| ADME/Pharmacokinetics |
Tesofensine is dissolved in 0.9% saline solution for in vivo administration. For in vitro use, it is soluble in DMSO at 2 mg/mL (6.09 mM) with ultrasonic and warming assistance. The compound should be stored at 4°C, protected from light, and in solvent at -80°C for up to 6 months. The threshold dose for inhibition of total food intake in DIO rats is 1.0 mg/kg. Detailed half-life, bioavailability, and metabolic pathway data are not extensively provided in the available literature.
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| Toxicity/Toxicokinetics |
Tesofensine is generally well-tolerated at therapeutic doses. In animal studies, no significant adverse effects are reported at the doses tested (0.1-3 mg/kg, s.c.). Common side effects associated with monoamine reuptake inhibitors may include gastrointestinal disturbances, insomnia, and cardiovascular effects, though specific toxicity data for Tesofensine are not detailed in the available references. Standard toxicology assessments would typically evaluate acute, subchronic, and chronic toxicity, as well as genotoxicity and reproductive toxicity.
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| References |
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| Additional Infomation |
Drug Indication
It has been studied for the treatment of Alzheimer's disease, Parkinson's disease, and obesity. Mechanism of Action Tessofencin is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). SNDRIs are a class of psychoactive antidepressants. They act on neurotransmitters in the brain, namely serotonin, norepinephrine, and dopamine. These three biological monoamines are associated with depression, and increasing the availability of these neurotransmitters in the brain is one approach to treating depression. Tesofensine (NS-2330) was originally developed for neurological indications but has shown significant potential as an anti-obesity agent due to its potent appetite-suppressing effects. It is a triple monoamine reuptake inhibitor that increases synaptic levels of dopamine, norepinephrine, and serotonin. The compound has completed clinical trials for obesity, demonstrating substantial weight loss. However, its development for obesity has been associated with cardiovascular safety concerns, including increased heart rate and blood pressure. No approved status is currently reported. Further clinical development may depend on managing these cardiovascular effects. |
| Molecular Formula |
C17H23CL2NO
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|---|---|
| Molecular Weight |
328.27662
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| Exact Mass |
327.116
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| CAS # |
195875-84-4
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| Related CAS # |
Related CAS#:402856-42-2
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| PubChem CID |
11370864
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| Appearance |
White to off-white solid powder
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| Density |
1.161 g/cm3
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| Boiling Point |
396.6ºC at 760 mmHg
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| Flash Point |
193.7ºC
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| LogP |
4.534
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
354
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CCOC[C@H]1[C@H]2CC[C@H](N2C)C[C@@H]1C3=CC(=C(C=C3)Cl)Cl
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| InChi Key |
VCVWXKKWDOJNIT-ZOMKSWQUSA-N
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| InChi Code |
InChI=1S/C17H23Cl2NO/c1-3-21-10-14-13(9-12-5-7-17(14)20(12)2)11-4-6-15(18)16(19)8-11/h4,6,8,12-14,17H,3,5,7,9-10H2,1-2H3/t12-,13+,14+,17+/m0/s1
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| Chemical Name |
(1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane
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| Synonyms |
Tesofensine NS-2330 NS2330 NS 2330
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~2 mg/mL (~6.09 mM)
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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 | 3.0462 mL | 15.2309 mL | 30.4618 mL | |
| 5 mM | 0.6092 mL | 3.0462 mL | 6.0924 mL | |
| 10 mM | 0.3046 mL | 1.5231 mL | 3.0462 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.
A multi-centre, double-blind, parallel-group, randomised, placebo-controlled study to investigate the safety and tolerability of 0.25, 0.5 and 1.0 mg NS 2330 orally and once daily during a 14-week treatment period as add-on to 10 mg donepezil once daily in patients with mild to moderate dementia of the Alzheimer's type.
CTID: null
Phase: Phase 2 Status: Completed
Date: 2004-08-09
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