| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Licostinel is a competitive, silent antagonist of the glycine site of the NMDA receptor (Kb = 5 nM). It functions as a silent antagonist, meaning it blocks receptor activation without producing intrinsic channel activation. It also antagonizes AMPA and kainate receptors at high concentrations (Kb = 0.9 µM and 2.5 µM, respectively).
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| ln Vitro |
In vitro, Licostinel demonstrates high binding affinity (Kb = 5 nM) at the NMDA receptor glycine site and functions as a silent antagonist. It is a glycine receptor antagonist with an IC50 of 59 nM. The compound selectively inhibits NMDA receptor activity without producing channel activation, making it a valuable tool for studying NMDA receptor physiology.
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| ln Vivo |
In vivo, Licostinel has demonstrated neuroprotective effects in preclinical models, including quantified infarct reduction in MCAO (middle cerebral artery occlusion) models. It showed a 2-hour therapeutic window and lack of psychotomimetic effects at clinical doses up to 3.0 mg/kg. The compound was advanced to Phase I/II clinical evaluation as a neuroprotective agent for ischemic stroke and traumatic brain injury.
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| Enzyme Assay |
In vitro receptor binding assays for Licostinel typically use membrane preparations from cells expressing NMDA receptors. Radiolabeled glycine or a glycine-site ligand is displaced by increasing concentrations of Licostinel to determine binding affinity (Ki). Non-specific binding is determined in the presence of excess unlabeled glycine. Bound radioactivity is measured by scintillation counting. Functional assays measure the compound's ability to inhibit NMDA receptor-mediated currents.
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| Cell Assay |
Cell-based electrophysiology assays for Licostinel involve recording NMDA receptor-mediated currents from cells expressing the receptor. Whole-cell patch-clamp is used to measure currents evoked by NMDA and glycine in the presence and absence of the compound. The compound's ability to inhibit glycine-dependent NMDA receptor activation is quantified. Schild analysis is performed to determine the mechanism of antagonism. Selectivity is assessed by testing against AMPA and kainate receptors.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [3]
Doses: 20, 40, 80 mg/kg intraperitoneal (ip) injection bolus 7 mg/kg/h, 30 minutes Route of Administration: intravenous (iv) (iv)injection bolus continuous Infusion Experimental Results: Dose-dependent reduction in depression spread rate and EEG activity in the rat brain. In vivo animal studies for Licostinel typically involve administering the compound to rodent models of ischemic stroke or traumatic brain injury. The compound is given intravenously or intraperitoneally at various doses. Infarct size is measured by histology or MRI. Neurological function is assessed using behavioral tests. The therapeutic window is determined by varying the time of administration relative to injury. Neuroprotection is the primary endpoint. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Licostinel are characteristic of small molecule NMDA receptor antagonists. The compound is able to cross the blood-brain barrier. Following administration, it is distributed to the brain, where it binds to NMDA receptors. Metabolism occurs primarily in the liver, with excretion through renal pathways. The compound has a half-life suitable for acute administration in neuroprotective studies.
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| Toxicity/Toxicokinetics |
Toxicological profile of Licostinel was evaluated in preclinical and clinical studies. The compound was generally well-tolerated, with no psychotomimetic effects observed at clinical doses up to 3.0 mg/kg. Common side effects were mild and transient. The compound's safety profile supported its advancement to Phase I/II clinical trials. However, development was ultimately discontinued.
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| References |
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| Additional Infomation |
Licostinel was advanced to Phase I/II clinical evaluation by Acea Pharmaceuticals, CoCensys, and Novartis as a neuroprotective agent for ischemic stroke and traumatic brain injury. While the compound was not ultimately commercialized, its well-documented pharmacological profile makes it a reference standard for glycine-site NMDA antagonism in preclinical neuroprotection research. It is a valuable tool for studying NMDA receptor pharmacology and neuroprotection.
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| Molecular Formula |
C8H3CL2N3O4
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|---|---|
| Molecular Weight |
276.029
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| Exact Mass |
274.95
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| CAS # |
153504-81-5
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| PubChem CID |
5486198
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| Appearance |
Light yellow to light brown solid powder
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| Density |
1.757g/cm3
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| Index of Refraction |
1.647
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| LogP |
1.954
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
17
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| Complexity |
386
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CHFSOFHQIZKQCR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H3Cl2N3O4/c9-2-1-3-5(6(4(2)10)13(16)17)12-8(15)7(14)11-3/h1H,(H,11,14)(H,12,15)
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| Chemical Name |
6,7-dichloro-5-nitro-1,4-dihydroquinoxaline-2,3-dione
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| Synonyms |
ACEA 1021; ACEA-1021; Licostinel
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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 : ~12.5 mg/mL (~45.28 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 | 3.6228 mL | 18.1140 mL | 36.2279 mL | |
| 5 mM | 0.7246 mL | 3.6228 mL | 7.2456 mL | |
| 10 mM | 0.3623 mL | 1.8114 mL | 3.6228 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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