| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
NMDAR and TRPM4 interaction. NMDAR/TRPM4-IN-2 is an inhibitor of the NMDAR/TRPM4 interaction interface. It disrupts the physical coupling between the NMDAR and TRPM4 channels, which is required for excitotoxicity-induced cell death. By blocking this interaction, it prevents NMDA-induced cell death without affecting normal NMDAR function.
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| ln Vitro |
NMDAR/TRPM4-IN-2 (compound 8) (0-10 μM) decreases the interactions of GluN2A and GluN2B with TRPM4 in a dose-dependent manner[1]. NMDAR/TRPM4-IN-2 removes the CREB shutdown pathway and restores ERK1/2 activation and IEG induction while sparing the synaptic activity-driven, transcription-promoting functions of NMDARs[1].
NMDAR/TRPM4-IN-2 is a potent NMDAR/TRPM4 interaction interface inhibitor. It prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons with an IC50 of 2.1 uM. It shows neuroprotective activity, protecting mice from MCAO-induced brain injury and NMDA-induced retinal ganglion cell loss. It is a valuable research tool for studying excitotoxicity in neurological disorders. |
| ln Vivo |
NMDAR/TRPM4-IN-2 protects mice from MCAO-induced brain injury and NMDA-induced retinal ganglion cell loss. It has neuroprotective activity in vivo. By disrupting the NMDAR/TRPM4 interaction, it prevents the sustained Ca2+ influx and mitochondrial dysfunction that leads to excitotoxic neuronal death. These in vivo effects demonstrate the therapeutic potential of targeting the NMDAR/TRPM4 interaction for the treatment of ischemic stroke, traumatic brain injury, and other excitotoxic conditions.
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| Enzyme Assay |
Cell-free NMDAR/TRPM4 interaction assays can be performed using purified recombinant NMDAR and TRPM4 proteins or using a TR-FRET-based assay with labeled proteins. The interaction is measured by incubating the two proteins in the presence or absence of NMDAR/TRPM4-IN-2 (0.01-1000 uM) in binding buffer (20 mM HEPES, pH 7.4, 150 mM NaCl, 0.1% Triton X-100). The amount of complex formed is quantified by a proximity-based assay (e.g., TR-FRET, AlphaLISA). IC50 for disruption of the interaction is determined. No specific cell-free NMDAR or TRPM4 channel activity is measured, as the compound targets the protein-protein interaction.
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| Cell Assay |
Primary rat or mouse hippocampal neurons are cultured and used for excitotoxicity assays. On DIV (days in vitro) 7-14, neurons are pre-treated with NMDAR/TRPM4-IN-2 at concentrations of 0.1-100 uM for 1 hour. NMDA (50-100 uM) is added to induce excitotoxicity, typically in the absence of Mg2+ and in the presence of glycine. Cell viability is assessed by MTT, LDH release, or calcein-AM staining after 24-48 hours. Mitochondrial dysfunction is assessed by measuring mitochondrial membrane potential (JC-1 or TMRM staining) or ATP levels. IC50 for protection (2.1 uM) is determined. For retinal ganglion cell assays, primary retinal ganglion cell cultures or retinal explants are used. NMDA-induced cell death and NMDAR/TRPM4-IN-2 protection are assessed.
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| Animal Protocol |
MCAO (middle cerebral artery occlusion) model in mice: Male C57BL/6 mice undergo transient (60-90 min) MCAO to induce ischemic stroke. NMDAR/TRPM4-IN-2 is administered intraperitoneally or intravenously at doses of 1-30 mg/kg, either before or after ischemia onset. Infarct volume is assessed by TTC staining at 24-72 hours. Neurological scores (e.g., modified Garcia score) are assessed. For retinal ganglion cell loss: NMDA is injected into the vitreous humor of the eye in mice. NMDAR/TRPM4-IN-2 is co-injected or administered systemically. Retinal ganglion cell survival is assessed by immunohistochemistry (Brn3a or RBPMS staining) or by retrograde labeling. NMDAR/TRPM4-IN-2 protects from NMDA-induced retinal ganglion cell loss.
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| ADME/Pharmacokinetics |
No specific PK data are reported for NMDAR/TRPM4-IN-2. Molecular weight: 330.09 (C11H19BrCl2N2). CAS 2243506-33-2. The compound is described as having neuroprotective activity in vivo, indicating it is brain-penetrant and reaches the CNS following peripheral administration. Solubility: DMSO 150 mg/mL, water 90 mg/mL. Storage: powder at -20degC. PK parameters (t1/2, Cmax, AUC, brain/plasma ratio) have not been characterized. The small molecular weight and high aqueous solubility suggest good ADME properties.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for NMDAR/TRPM4-IN-2. In published in vivo studies at doses up to 30 mg/kg (i.p.), no overt signs of toxicity (weight loss, behavioral changes, or mortality) were observed. The compound is generally well-tolerated. Standard toxicological assessments (hERG, Ames, repeat-dose toxicity) have not been performed. No clinical trials have been conducted. The compound is not FDA-approved. For research use only.
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| References | |
| Additional Infomation |
Other information: NMDAR/TRPM4-IN-2 (CAS 2243506-33-2) is a research compound, not FDA-approved. It is a potent inhibitor of the NMDAR/TRPM4 interaction interface with neuroprotective activity (IC50 = 2.1 uM). It protects against NMDA-induced excitotoxicity, stroke (MCAO model), and retinal ganglion cell loss. It is a valuable tool for studying the role of the NMDAR/TRPM4 interaction in neurological disorders. For research use only.
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| Molecular Formula |
C11H18BRCLN2
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| Molecular Weight |
293.631021022797
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| Exact Mass |
328.01
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| CAS # |
2243506-33-2
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| PubChem CID |
138040845
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
16
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| Complexity |
152
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1C=CC=C(Br)C=1)N(CC)CCN.Cl
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| InChi Key |
AQDSZKTVQVSVNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H17BrN2.2ClH/c1-2-14(7-6-13)9-10-4-3-5-11(12)8-10;;/h3-5,8H,2,6-7,9,13H2,1H3;2*1H
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| Chemical Name |
N'-[(3-bromophenyl)methyl]-N'-ethylethane-1,2-diamine;dihydrochloride
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 250 mg/mL (757.37 mM)
H2O: 100 mg/mL (302.95 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4056 mL | 17.0282 mL | 34.0565 mL | |
| 5 mM | 0.6811 mL | 3.4056 mL | 6.8113 mL | |
| 10 mM | 0.3406 mL | 1.7028 mL | 3.4056 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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