| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
NMDA (N-methyl-D-aspartic acid) receptor glycine modulatory site. Gavestinel is a selective and potent antagonist at this site.
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| ln Vitro |
Gavestinel is a selective and potent antagonist of the NMDA receptor glycine site. By blocking the glycine co-agonist site, it inhibits NMDA receptor activation and reduces excitatory neurotransmission. This mechanism is thought to underlie its neuroprotective effects in models of excitotoxicity and ischemia. The compound has been shown to reduce infarct volume in animal models of stroke.
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| ln Vivo |
In vivo, gavestinel has been studied extensively in preclinical models of stroke and excitotoxicity. It has demonstrated neuroprotective effects in animal models of focal cerebral ischemia. However, in clinical trials (the GAIN International trial), gavestinel did not show significant efficacy in improving functional outcomes in patients with acute stroke. The GAIN MRI Substudy evaluated the effect of gavestinel on cerebral infarcts in acute stroke patients.
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| Enzyme Assay |
In vitro receptor binding assays for gavestinel are performed to evaluate its affinity for the NMDA receptor glycine site. Radioligand binding studies using membrane preparations from brain tissue or cells expressing NMDA receptors are conducted. The compound's ability to displace a specific radiolabeled glycine site ligand, such as [3H]-MDL-105,519 or [3H]-glycine, is measured to calculate its binding affinity.
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| Cell Assay |
In vitro cell-based assays are conducted using cells expressing recombinant NMDA receptors. The cells are treated with gavestinel in the presence of glutamate and glycine, and receptor activity is measured by assessing downstream signaling events such as calcium mobilization or electrophysiological responses. The antagonism of glycine-induced potentiation of NMDA receptor activity is quantified.
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| Animal Protocol |
In vivo studies were conducted in animal models of stroke to evaluate the neuroprotective effects of gavestinel. The compound was administered via various routes, and its effects on infarct volume, neurological deficits, and functional outcomes were assessed. Clinical trials were also conducted in patients with acute stroke.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Gavestin's known metabolites include garvestin 4-O-acylglucuronide and p-hydroxygarvestin. Gavestinel is metabolized by CYP2C9 via aromatic hydroxylation to p-hydroxygavestinel. The compound has been studied in clinical trials, and its pharmacokinetic properties have been characterized in humans. However, detailed pharmacokinetic parameters are not publicly available. |
| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for gavestinel. As an NMDA receptor antagonist, its toxicity profile would be expected to be related to its mechanism of action. Excessive NMDA receptor inhibition can impair synaptic plasticity and cognitive function. The compound was generally well-tolerated in clinical trials.
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| References | |
| Additional Infomation |
3-(3-anilino-3-oxopropyl-1-enyl)-4,6-dichloro-1H-indole-2-carboxylic acid is an indole carboxylic acid. It is a highly effective and selective non-competitive antagonist that acts on the glycine binding site (Kd = 0.8 nM) in the NMDA receptor channel complex, which is insensitive to strychnine. Garvistine exhibits more than 1000 times higher selectivity for NMDA, AMPA, and fumaryl binding sites compared to its NMDA, AMPA, and fumaryl binding sites, and also demonstrates high oral bioavailability and potent in vivo activity.
Gavestinel (GV 150526) is a selective and potent antagonist of the NMDA receptor glycine site that was investigated for neuroprotection in acute stroke. Despite promising preclinical data, clinical trials did not demonstrate significant efficacy. The compound is a research tool and is not approved for clinical use. It is also known as GV 150526, GV-150526X, and has the UNII 318X4QY113. The compound has the CAS number 153436-22-7. |
| Molecular Formula |
C18H12CL2N2O3
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|---|---|
| Molecular Weight |
375.21
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| Exact Mass |
396.004
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| CAS # |
153436-22-7
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| Related CAS # |
Gavestinel sodium salt;153436-38-5
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| PubChem CID |
6450546
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.561g/cm3
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| Boiling Point |
701.1ºC at 760mmHg
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| Flash Point |
377.8ºC
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| Vapour Pressure |
1.24E-20mmHg at 25°C
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| LogP |
3.563
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
536
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)NC(=O)/C=C/C2=C(NC3=C2C(=CC(=C3)Cl)Cl)C(=O)O
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| InChi Key |
WZBNEZWCNKUOSM-VOTSOKGWSA-N
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| InChi Code |
InChI=1S/C18H12Cl2N2O3/c19-10-8-13(20)16-12(17(18(24)25)22-14(16)9-10)6-7-15(23)21-11-4-2-1-3-5-11/h1-9,22H,(H,21,23)(H,24,25)/b7-6+
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| Chemical Name |
3-[(E)-3-anilino-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylic acid
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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: 125 mg/mL (333.15 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 | 2.6652 mL | 13.3259 mL | 26.6517 mL | |
| 5 mM | 0.5330 mL | 2.6652 mL | 5.3303 mL | |
| 10 mM | 0.2665 mL | 1.3326 mL | 2.6652 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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