1. Membrane Transporter/Ion Channel Neuronal Signaling
  2. iGluR
  3. QNZ46

QNZ46 is a highly selective noncompetitive NMDA receptor antagonist targeting GluN2C/D (IC50=3.9 μM), GluN1/GluN2C (IC50=7.1 μM), and GluN1/GluN2D (IC50=182 μM) subunits. QNZ46 inhibits glutamate-mediated calcium influx, thereby blocking excitotoxicity. QNZ46 is membrane permeable and can cross the blood-brain barrier, where it inhibits myelin damage and axonal degeneration.

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QNZ46 Chemical Structure

QNZ46 Chemical Structure

CAS No. : 1237744-13-6

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Description

QNZ46 is a highly selective noncompetitive NMDA receptor antagonist targeting GluN2C/D (IC50=3.9 μM), GluN1/GluN2C (IC50=7.1 μM), and GluN1/GluN2D (IC50=182 μM) subunits. QNZ46 inhibits glutamate-mediated calcium influx, thereby blocking excitotoxicity. QNZ46 is membrane permeable and can cross the blood-brain barrier, where it inhibits myelin damage and axonal degeneration[1][2][3].

IC50 & Target

NMDA Receptor

 

Cellular Effect
Cell Line Type Value Description References
Oocyte IC50
> 300 μM
Compound: 46
Antagonist activity at rat recombinant NR1-NR2B receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
Antagonist activity at rat recombinant NR1-NR2B receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
[PMID: 20684595]
Oocyte IC50
> 300 μM
Compound: 46
Antagonist activity at rat recombinant GLuR1 expressed in Xenopus oocytes assessed as inhibition of glutamate-induced current by two-electrode voltage-clamp electrophysiology
Antagonist activity at rat recombinant GLuR1 expressed in Xenopus oocytes assessed as inhibition of glutamate-induced current by two-electrode voltage-clamp electrophysiology
[PMID: 20684595]
Oocyte IC50
229 μM
Compound: 46
Antagonist activity at rat recombinant NR1-NR2A receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
Antagonist activity at rat recombinant NR1-NR2A receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
[PMID: 20684595]
Oocyte IC50
3 μM
Compound: 46
Antagonist activity at rat recombinant NR1-NR2D receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
Antagonist activity at rat recombinant NR1-NR2D receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
[PMID: 20684595]
Oocyte IC50
6 μM
Compound: 46
Antagonist activity at rat recombinant NR1-NR2C receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
Antagonist activity at rat recombinant NR1-NR2C receptor expressed in Xenopus oocytes at holding potential of -40mV by two-electrode voltage-clamp electrophysiology
[PMID: 20684595]
In Vitro

Cell viability assay: QNZ46 (1-20 μM; 48 h) significantly reduces neuronal cell viability, and the inhibition rate was positively correlated with the concentration[2].
Immunofluorescence assay: QNZ46 (50 μM; 2 h) reduces myelin swelling in the myelin injury model and protected structural integrity[2].
WB assay: QNZ46 (10 μM; 24 h) decreases MLKL phosphorylation and RIP1 expression, may cause suppression of necroptosis pathways[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: HEK293 cells expressing GluN1/GluN2D receptors
Concentration: 1-20 μM
Incubation Time: 48 h
Result: Reduced cell viability by 23-88% (IC50=3.9 μM), consistent with noncompetitive NMDA receptor inhibition.

Immunofluorescence[2]

Cell Line: Primary oligodendrocytes
Concentration: 50 μM
Incubation Time: 24 h
Result: Reduced ischemic injury-induced myelin decompaction (G-ratio increase from 0.67 to 0.90 μm) and preserved FluoroMyelin Red staining intensity.

Western Blot Analysis[2]

Cell Line: Rat optic nerve (RON)
Concentration: 10 μM
Incubation Time: 24 h
Result: Decreased phosphorylated MLKL (30% reduction) and RIP1 expression (40% reduction), indicating suppression of necroptosis pathways[2].
In Vivo

Ischemic stroke model: QNZ46 (20 mg/kg; i.p.; single administration) significantly reduces brain lesion volume and improved neurological function in transient middle cerebral artery occlusion (tMCAO) mice[2].
EAE model: QNZ46 (2 mg/kg+1 mg/kg CP465022; i.p.; once a day for 28 days) significantly reduces clinical scores in experimental autoimmune encephalomyelitis (EAE) mice and protected small-diameter myelinated axons in the spinal cord[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 mice (male, 25-30 g, 8-12 weeks) + transient middle cerebral artery occlusion (tMCAO)[2]
Dosage: 20 mg/kg (50% DMSO/β-cyclodextrin)
Administration: Single i.p. injection 120 min prior to ischemia
Result: Reduced infarct volume by 68%, preserved myelinated axons in the external capsule, and improved neurological performance.
Animal Model: Animal Model: . C57BL/6 mice (female, 20-22 g, 8-12 weeks) + experimental autoimmune encephalomyelitis (EAE)[3]
Dosage: 2 mg/kg QNZ46 + 1 mg/kg CP465022 (0.5% methyl cellulose)
Administration: Daily i.p. injections from day 0 to day 28 post-immunization
Result: Combined QNZ46/CP465022 treatment reduced clinical severity and preserved small-diameter myelinated axons in spinal cord.
Molecular Weight

443.41

Formula

C24H17N3O6

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(O)C1=CC=C(N2C(/C=C/C3=CC=CC([N+]([O-])=O)=C3)=NC4=C(C=C(OC)C=C4)C2=O)C=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 4 mg/mL (9.02 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.2552 mL 11.2762 mL 22.5525 mL
5 mM 0.4510 mL 2.2552 mL 4.5105 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.2552 mL 11.2762 mL 22.5525 mL 56.3812 mL
5 mM 0.4510 mL 2.2552 mL 4.5105 mL 11.2762 mL
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Product Name:
QNZ46
Cat. No.:
HY-15703
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