| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
(+)-KCC2 blocker 1 targets the K+-Cl- cotransporter KCC2, a neuron-specific chloride transporter that plays a critical role in maintaining low intracellular chloride levels. KCC2 is essential for inhibitory neurotransmission mediated by GABA and glycine receptors. By blocking KCC2, the compound increases intracellular chloride levels, reducing the efficacy of inhibitory neurotransmission. This mechanism is important for studying neuronal excitability, synaptic plasticity, and neurological disorders.
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| ln Vitro |
(+)-KCC2 Blocker 1 ((+)-13) is the KCC2 Blocker 1 enantiomer, and its efficacy is 100 times different than that of the enantiomer (-)-KCC2 Blocker 1 ((−)-13)) [1].
(+)-KCC2 blocker 1 exhibits potent in vitro activity as a KCC2 blocker. It has an IC50 of 0.4 μM for KCC2. The (+)-enantiomer possesses a 100-fold difference in potency compared to the (-)-enantiomer, demonstrating stereospecific activity. In cellular assays, the compound increases intracellular chloride levels and reduces GABA-mediated inhibition. These in vitro activities confirm its utility as a research tool for studying KCC2 function. |
| ln Vivo |
In vivo activity of (+)-KCC2 blocker 1 has been studied in animal models of neurological disorders. By blocking KCC2, the compound modulates neuronal excitability and synaptic inhibition. This may have implications for studying conditions such as epilepsy, neuropathic pain, and schizophrenia. However, detailed in vivo data are limited, as the compound is primarily used as a research tool.
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| Enzyme Assay |
In vitro transporter assays for (+)-KCC2 blocker 1 involve measuring its inhibition of KCC2-mediated chloride transport. These assays typically use cells expressing recombinant KCC2 and a fluorescent chloride indicator. Cells are treated with varying concentrations of the compound, and chloride influx or efflux is measured. The IC50 (0.4 μM) is determined. These assays confirm the compound’s mechanism as a KCC2 blocker.
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| Cell Assay |
In vitro cellular assays for (+)-KCC2 blocker 1 are conducted in neurons or cells expressing KCC2. Cells are treated with the compound at various concentrations, and intracellular chloride levels are measured using fluorescent indicators. GABA-mediated inhibitory currents are measured by electrophysiology. Cell viability is assessed to ensure that observed effects are not due to cytotoxicity. These assays characterize the compound’s cellular effects on chloride homeostasis and neuronal inhibition.
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| Animal Protocol |
In vivo animal experiments with (+)-KCC2 blocker 1 are conducted in rodent models of neurological disorders. The compound is administered via intracerebroventricular (ICV) injection or systemic administration. Behavioral assays, seizure models, and pain models are used to assess the effects of KCC2 blockade. Electrophysiological recordings in vivo may be performed to measure neuronal excitability. These studies elucidate the role of KCC2 in brain function and disease.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for (+)-KCC2 blocker 1 are limited. The compound has a molecular weight of 415.5 and is soluble in DMSO. Its bioavailability and half-life have not been extensively characterized. The compound is typically stored at -20°C. Further PK studies would be needed to support any potential therapeutic development.
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| Toxicity/Toxicokinetics |
(+)-KCC2 blocker 1 is considered to have low toxicity based on its use as a research compound. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References |
[1]. Pégurier C, et al. Benzyl prolinate derivatives as novel selective KCC2 blockers. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2542-5.
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| Additional Infomation |
(+)-KCC2 blocker 1 is a selective K+-Cl- cotransporter KCC2 blocker with an IC50 of 0.4 μM. It is a benzyl prolinate and an enantiomer of KCC2 blocker 1. The (+)-enantiomer possesses a 100-fold difference in potency compared to the (-)-enantiomer. The compound is used in neuroscience research to study KCC2 function in chloride homeostasis and synaptic inhibition. It is available in high purity (>99%) for research applications. Its selectivity and potency make it a valuable tool for studying neuronal inhibition and neurological disorders.
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| Molecular Formula |
C22H25NO5S
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|---|---|
| Molecular Weight |
415.50
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| Exact Mass |
415.145
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| CAS # |
1228439-71-1
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| Related CAS # |
KCC2 blocker 1;1228439-36-8
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| PubChem CID |
46866400
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| Appearance |
White to off-white solid
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| LogP |
2.7
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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 |
7
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| Heavy Atom Count |
29
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| Complexity |
687
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(OCC1=CC=CC=C1)C2(CC3=CC=C(S(=O)(C)=O)C=C3)N(C(C)=O)CCC2
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| InChi Key |
XFXZWVGQXNFWDE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H25NO5S/c1-17(24)23-14-6-13-22(23,21(25)28-16-19-7-4-3-5-8-19)15-18-9-11-20(12-10-18)29(2,26)27/h3-5,7-12H,6,13-16H2,1-2H3
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| Chemical Name |
benzyl 1-acetyl-2-[(4-methylsulfonylphenyl)methyl]pyrrolidine-2-carboxylate
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~240.7 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4067 mL | 12.0337 mL | 24.0674 mL | |
| 5 mM | 0.4813 mL | 2.4067 mL | 4.8135 mL | |
| 10 mM | 0.2407 mL | 1.2034 mL | 2.4067 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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