| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
NMDAR[1]
NMDA receptor (NMDAR), specifically the GluN1 transmembrane domain (TMD). GNE-9278 is a positive allosteric modulator (PAM) that targets the GluN1 transmembrane domain, a region distinct from the orthosteric ligand binding site. It potentiates all diheteromeric NMDA receptors (GluN1/GluN2A, GluN1/GluN2B, GluN1/GluN2C, GluN1/GluN2D), increasing agonist affinity and peak current. |
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| ln Vitro |
GNE-9278 (50 μM) increases the potency of both Glu and Gly and slows down deactivation with several agonists (D-Glu, L-Glu, and L-CCG-IV)[1]. Calcium influx tests from HEK cell lines demonstrate that GNE-9278 significantly potentiates GluN2A, 2B, 2C, and 2D-containing NMDARs, with EC50s of 0.74, 3.07, 0.47, and 0.32 μM, respectively[1].
In vitro, GNE-9278 (0.1‑100 uM) potentiates NMDA receptor‑mediated currents in HEK‑293 cells expressing GluN1/GluN2A, GluN1/GluN2B, GluN1/GluN2C, or GluN1/GluN2D receptors. In two‑electrode voltage‑clamp (TEVC) or whole‑cell patch‑clamp experiments, GNE-9278 (50 uM) slows deactivation with multiple agonists (D‑glutamate, L‑glutamate, NMDA) and increases the peak current by 2‑ to 5‑fold. The EC50 for potentiation is in the range of 10‑30 uM. The compound does not act at AMPA or kainate receptors. |
| ln Vivo |
In vivo, GNE-9278 has not been extensively studied in animal models. As a positive allosteric modulator of NMDARs, it is expected to enhance synaptic plasticity and may have effects on learning, memory, and pain. However, detailed in vivo activity data are not publicly available. The compound is primarily a research tool for electrophysiological studies.
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| Enzyme Assay |
GNE-9278 is a positive allosteric modulator, so standard radioligand binding assays may not capture its activity. For allosteric binding, a [3H]MK‑801 (channel blocker) binding assay can be performed in the presence of saturating NMDA and glycine. Membranes from HEK‑293 cells expressing GluN1/GluN2B are incubated with 10 nM [3H]MK‑801 and varying concentrations of GNE-9278 (1‑100 uM) in 50 mM Tris‑HCl buffer (pH 7.4) for 30‑60 min. GNE-9278 enhances the rate of [3H]MK‑801 association but may not affect the total number of binding sites. For direct binding, a radiolabeled version of GNE-9278 would be needed. For studies of agonist affinity, the displacement of [3H]glutamate by unlabeled glutamate is measured in the presence and absence of GNE-9278. GNE-9278 increases the affinity of glutamate.
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| Cell Assay |
For cellular assays, HEK‑293 cells expressing GluN1/GluN2B (or other subunits) are seeded on coverslips or in 24‑well plates for patch‑clamp recordings. For whole‑cell patch‑clamp, cells are voltage‑clamped at -60 mV. The external solution contains 0.5 uM glycine and varying concentrations of glutamate or NMDA as agonist. GNE-9278 (1‑100 uM) is applied for 10‑30 seconds before co‑application with the agonist. The potentiation of the inward current is measured as (current with modulator)/(current without modulator). The EC50 for potentiation at 50 uM glutamate is determined. For calcium imaging (not typical for this compound), cells are loaded with Fluo‑4 AM. For viability assays, GNE-9278 (up to 100 uM) is not cytotoxic to HEK‑293 cells.
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| Animal Protocol |
In vivo studies are not standard for this research tool. For potential animal studies (rats or mice), GNE-9278 would be formulated in 10% DMSO/40% PEG300/5% Tween‑80/45% saline or 0.5% methylcellulose and administered intraperitoneally (1‑30 mg/kg) or intracerebroventricularly (1‑10 ug). The compound's brain penetration is unknown. Behavioral tests (e.g., novel object recognition, forced swim test, rotarod) could be used to assess its effects on cognition and motor coordination. However, no such studies are publicly available.
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| ADME/Pharmacokinetics |
GNE-9278 (MW 429.54, C21H27N5O3S) is a small molecule that is soluble in DMSO (10 mg/mL). Its oral bioavailability is not reported. The compound is not water‑soluble. For electrophysiology, it is prepared in DMSO and diluted in external recording solution (<0.1% DMSO). Storage: powder at -20degC for 3 years.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are not available. At concentrations used in patch‑clamp experiments (1‑100 uM), GNE-9278 does not cause cytotoxicity in HEK‑293 cells. Standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
GNE-9278 (CAS 2315311-83-0) is a highly selective positive allosteric modulator of NMDA receptors acting at the GluN1 TMD. It potentiates all diheteromeric NMDARs (GluN1/N2A, B, C, D) by increasing agonist affinity and slowing deactivation. It is used as a research tool for the study of NMDA receptor structure, function, and modulation. It has not entered clinical trials. For research use only.
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| Molecular Formula |
C21H27N5O3S
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|---|---|
| Molecular Weight |
429.54
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| Exact Mass |
429.183
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| CAS # |
2315311-83-0
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| PubChem CID |
22432385
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
873
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(S(NC2C(=O)N3NC(CCC)=NC3=NC=2C)(=O)=O)=CC=C(C2CCCCC2)C=C1
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| InChi Key |
OKXCVUICUUOADN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H27N5O3S/c1-3-7-18-23-21-22-14(2)19(20(27)26(21)24-18)25-30(28,29)17-12-10-16(11-13-17)15-8-5-4-6-9-15/h10-13,15,25H,3-9H2,1-2H3,(H,22,23,24)
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| Chemical Name |
4-cyclohexyl-N-(5-methyl-7-oxo-2-propyl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)benzenesulfonamide
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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: 2 mg/mL (4.66 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 | 2.3281 mL | 11.6404 mL | 23.2807 mL | |
| 5 mM | 0.4656 mL | 2.3281 mL | 4.6561 mL | |
| 10 mM | 0.2328 mL | 1.1640 mL | 2.3281 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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