| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
NMDA receptors (NMDAR), specifically the GluN1/GluN2 subunits. (S,S)-GNE 5729 is a positive allosteric modulator that binds to a site distinct from glutamate and glycine, potentiating receptor activity by increasing channel open probability and/or altering desensitization kinetics. As an enantiomer, its potency may differ from the racemate or other enantiomers.
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|---|---|
| ln Vitro |
No specific in vitro activity data for (S,S)-GNE 5729 is reported. GNE 5729 itself potentiates NMDA receptor currents at nanomolar concentrations in HEK293 cells expressing recombinant NMDARs. The (S,S)-enantiomer may be less active than the (R,R)-enantiomer, but this remains to be determined. It serves as a control to assess stereoselectivity of NMDA receptor modulation.
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| ln Vivo |
No in vivo activity for the isolated (S,S)-enantiomer is reported. As a PAM, GNE 5729 enhances long‑term potentiation and improves cognitive function in rodent models of schizophrenia and Alzheimer's disease at doses of 1-10 mg/kg (i.p.). The (S,S)-enantiomer may have distinct in vivo activity due to stereoselective metabolism and target binding.
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| Enzyme Assay |
Binding studies are typically performed using radioligand binding assays. The compound is dissolved in DMSO and incubated (0.1 nM-100 microM) with membrane preparations from HEK293 cells expressing human NMDARs (GluN1/GluN2A or GluN1/GluN2B) in the presence of 1 uM glutamate and 0.1 uM glycine. Competition binding is assessed using a labeled PAM (e.g., 3H‑GNE 5729). After incubation (1 hour, 22degC), bound radioactivity is counted. IC50 is calculated. Patch‑clamp electrophysiology is used to confirm modulation.
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| Cell Assay |
HEK293 cells stably expressing NMDARs (GluN1/GluN2B) are seeded in 96‑well plates. Cells are loaded with a calcium‑sensitive dye (Fluo‑4 AM) and treated with (S,S)-GNE 5729 (0.1 nM-10 uM) for 5 minutes, then stimulated with 100 uM glutamate and 10 uM glycine. Fluorescence is measured at 488 nm excitation and 525 nm emission to quantify calcium influx. Concentration‑response curves yield EC50 values for potentiation of receptor activity.
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| Animal Protocol |
(S,S)-GNE 5729 is administered to male C57BL/6 mice (1-10 mg/kg; i.p.) in vehicle (10% DMSO, 10% Tween 80, 80% saline). Cognitive function is assessed 1 hour post‑dose using the novel object recognition test or Morris water maze. Long‑term potentiation can be recorded from hippocampal slices of treated mice. Plasma and brain levels of the enantiomer are measured by LC‑MS. The (S,S)-enantiomer may be used as a negative control in these studies.
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| ADME/Pharmacokinetics |
No specific PK data for the isolated (S,S)-enantiomer is reported. GNE 5729 has high brain permeability (brain/plasma ratio ~1.0), moderate clearance, and a half‑life of 2-4 hours in rodents. The (S,S)-enantiomer may have a different metabolic profile. The compound is metabolized by CYP3A4 and excreted via bile.
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| Toxicity/Toxicokinetics |
No toxicity data specific to (S,S)-GNE 5729 is available. GNE 5729 has no acute toxicity in rodents at doses up to 100 mg/kg. The (S,S)-enantiomer is expected to have a similar safety margin, but this requires confirmation. Chronic toxicity studies have not been performed.
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| References |
[1]. Matthew Volgraf, et al. Pyridopyrimidinones and their use as nmda receptor modulators. WO2016166078A1.
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| Additional Infomation |
(S,S)-GNE 5729 is the (1S,2S) enantiomer of GNE 5729. Its IUPAC name is (1S,2S)-2-(7-chloro-2-((5-chloro-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-6-yl)cyclopropane-1-carbonitrile. It is a research chemical for studying NMDA receptor PAM stereochemistry. Not approved for clinical use. Molecular formula: C17H10Cl2F3N5O; molecular weight: 428.20.
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| Molecular Formula |
C17H10CL2F3N5O
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|---|---|
| Molecular Weight |
428.195411205292
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| Exact Mass |
427.021
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| CAS # |
2026636-06-4
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| PubChem CID |
140869608
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
900
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1[C@@H]([C@H]1C2=C(C=CC3=NC(=CC(=O)N32)CN4C(=CC(=N4)C(F)(F)F)Cl)Cl)C#N
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| InChi Key |
GPMGDUIAVSFGGH-SCZZXKLOSA-N
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| InChi Code |
InChI=1S/C17H10Cl2F3N5O/c18-11-1-2-14-24-9(7-26-13(19)5-12(25-26)17(20,21)22)4-15(28)27(14)16(11)10-3-8(10)6-23/h1-2,4-5,8,10H,3,7H2/t8-,10+/m1/s1
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| Chemical Name |
(1S,2S)-2-[7-chloro-2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxopyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.3354 mL | 11.6768 mL | 23.3536 mL | |
| 5 mM | 0.4671 mL | 2.3354 mL | 4.6707 mL | |
| 10 mM | 0.2335 mL | 1.1677 mL | 2.3354 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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