| Size | Price | Stock | Qty |
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| Targets |
EAAT2
EAAT2 activator 1 specifically targets the excitatory amino acid transporter 2 (EAAT2, also known as GLT-1). It acts as a pharmacological activator of the transporter, meaning it enhances the rate at which EAAT2 can remove glutamate from the synaptic cleft. This mechanism is considered a promising therapeutic strategy for reducing glutamate-mediated excitotoxicity. The exact molecular binding site on the transporter has not been fully elucidated, but its activity is measured by its ability to increase EAAT2 protein levels and glutamate uptake capacity.. |
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| ln Vitro |
In vitro, EAAT2 activator 1 has been shown to increase EAAT2 protein levels in mouse primary astrocytes. At a concentration of 10 uM, it induces a 2.0-fold increase in EAAT2 expression after 24 hours of treatment compared to control levels.. This increase is dose-dependent, meaning higher concentrations lead to a greater elevation of EAAT2 protein levels.. By raising EAAT2 expression, the compound enhances the capacity of astrocytes to clear glutamate from the extracellular space.
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| ln Vivo |
Specific in vivo activity data for EAAT2 activator 1 is not detailed in the provided search results. However, based on its mechanism as an EAAT2 activator, it is hypothesized to be neuroprotective in animal models of neurological diseases characterized by glutamate excitotoxicity, such as amyotrophic lateral sclerosis (ALS), epilepsy, stroke, and Alzheimer‘s disease. It would be evaluated for its ability to reduce neuronal damage, improve survival, and enhance behavioral outcomes in these models.
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| Enzyme Assay |
Given that EAAT2 activator 1 functions as a transcriptional or post-translational activator to increase EAAT2 protein levels, standard cell-free enzyme/receptor binding assays do not apply. Instead, the primary in vitro assay is an immunoblotting (Western blot) or ELISA-based assay to measure EAAT2 protein expression. Cell lysates from compound-treated primary astrocytes are separated by SDS-PAGE, transferred to a membrane, and probed with a specific anti-EAAT2 antibody. The signal is quantified by densitometry and normalized to a loading control (e.g., beta-actin or GAPDH) to determine the fold increase in EAAT2 protein levels..
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| Cell Assay |
The in vitro cellular assay for EAAT2 activator 1 involves the use of mouse primary astrocytes. Cortices are dissected from 1-3 day old mouse pups, and astrocytes are isolated and cultured in DMEM/F12 medium with 10% FBS. The astrocytes are seeded in 6-well plates and cultured until they reach 90% confluency (approximately 10-14 days). The culture medium is then replaced with medium containing varying concentrations of EAAT2 activator 1 (1, 3, 10 uM) and incubated for 24 hours. Following treatment, the cells are lysed, and total protein is extracted. EAAT2 protein levels are quantified by Western blotting using a specific anti-EAAT2 antibody and normalized to a loading control (e.g., GAPDH or beta-actin). The fold change in EAAT2 expression relative to the untreated control is calculated from densitometric analysis (e.g., at 10 uM, a 2.0-fold increase is observed)..
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| Animal Protocol |
An in vivo protocol for EAAT2 activator 1 would involve a mouse model of a neurodegenerative disease. For example, in the SOD1-G93A transgenic mouse model of ALS, mice are orally dosed with EAAT2 activator 1 (e.g., 10-100 mg/kg) daily starting at 50 days of age (pre-symptomatic stage). Disease progression is monitored by measuring body weight, motor function (rotarod latency, grip strength), and survival time. At the end-stage (approximately 120-150 days), lumbar spinal cords are harvested. EAAT2 protein levels in the spinal cord homogenates are measured by Western blotting to confirm target engagement. Histological analysis of the spinal cord (Nissl staining) is performed to quantify motor neuron survival. The compound would be expected to delay disease onset, prolong survival, and increase motor neuron counts.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for EAAT2 activator 1 is not available. As a small molecule with a molecular weight of 331.79 g/mol and a LogP value of 4.4, it is lipophilic and expected to cross the blood-brain barrier (BBB).. A standard PK study would involve administering the compound to mice via oral gavage (10-50 mg/kg) and analyzing plasma and brain concentrations by LC-MS/MS to determine key parameters such as T1/2, Cmax, AUC, and brain-to-plasma ratio (Kp). For in vivo formulation, it is typically dissolved in DMSO and then diluted in a vehicle such as 5% DMSO/40% PEG300/5% Tween-80/50% ddH2O.
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| Toxicity/Toxicokinetics |
Specific toxicological data for EAAT2 activator 1 is not available. As an EAAT2 activator that enhances glutamate uptake, the primary safety concern is the opposite of EAAT2 inhibition (which causes excitotoxicity). Excessive activation of EAAT2 could theoretically lead to reduced synaptic glutamate levels, which may interfere with normal glutamatergic transmission and cause sedation or motor impairment. Standard safety assessment would include a 14-day repeat-dose oral toxicity study in rats to determine the No-Observed-Adverse-Effect Level (NOAEL) and to evaluate for any signs of neurotoxicity or CNS depression.
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| References | |
| Additional Infomation |
EAAT2 activator 1 is a research-grade chemical and is not approved for clinical use. It is a unique small molecule tool that increases EAAT2 protein expression, which is a promising therapeutic strategy for various neurological disorders involving glutamate excitotoxicity, such as amyotrophic lateral sclerosis (ALS), epilepsy, Alzheimer‘s disease, and stroke. Its ability to boost the primary glutamate clearance mechanism in the brain makes it a valuable compound for validating EAAT2 as a therapeutic target. It is for research use only.
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| Molecular Formula |
C16H11CLFN3S
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|---|---|
| Molecular Weight |
331.795044183731
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| Exact Mass |
331.034
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| CAS # |
892415-28-0
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| PubChem CID |
20900510
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| Appearance |
Light brown to brown solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
349
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C(CSC2C=CC(C3C=CC=CN=3)=NN=2)=C(Cl)C=CC=1
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| InChi Key |
DCLFFJASADCESO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11ClFN3S/c17-12-4-3-5-13(18)11(12)10-22-16-8-7-15(20-21-16)14-6-1-2-9-19-14/h1-9H,10H2
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| Chemical Name |
3-[(2-chloro-6-fluorophenyl)methylsulfanyl]-6-pyridin-2-ylpyridazine
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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: 25 mg/mL (75.35 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.67 mg/mL (5.03 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 sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0139 mL | 15.0693 mL | 30.1386 mL | |
| 5 mM | 0.6028 mL | 3.0139 mL | 6.0277 mL | |
| 10 mM | 0.3014 mL | 1.5069 mL | 3.0139 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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