| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary molecular target of Tat-NR2B9c TFA is postsynaptic density-95 (PSD-95), a scaffolding protein that organizes signaling complexes at excitatory synapses. PSD-95 interacts with the C-terminus of NMDA receptor subunits (NR2A and NR2B) and with neuronal nitric oxide synthase (nNOS), coupling NMDA receptor activation to NO production and excitotoxic signaling. Tat-NR2B9c TFA inhibits PSD-95d2 with an EC50 of 6.7 nM and inhibits NR2A and NR2B binding to PSD-95 with IC50 values of 0.5 µM and 8 µM, respectively. The peptide also inhibits nNOS/PSD-95 interaction. By disrupting these interactions, Tat-NR2B9c TFA prevents the activation of NMDA-induced NADPH oxidase in neurons, thereby blocking the production of superoxide and reducing ischemic injury after stroke.
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| ln Vitro |
Tat-NR2B9c, a PSD-95 benchmark, exhibits domain affinity in comparison to PSD-95d1 (EC 50, 0.67 μM) with an EC50 of 6.7 nM for PSD-95d2. With an IC50 of 0.5 μM, approximately 8 μM, and 0.75 μM, respectively, Tat-NR2B9c inhibits the binding of NMDAR2A, NMDAR2B, and NMDAR2C to PSD-95. Moreover, Tat-NR2B9c, with an IC50 of around 0.2 μM, inhibits the PSD-95 and nNOS interaction [1]. While NMDA-induced p38 activation in YAC128 striatum is reduced by around 50% when Tat-NR2B9c lowers PSD-95 binding to GluN2B in YAC128 striatum, NMDA-induced JNK activation is unaffected [2].
In vitro studies demonstrate that Tat-NR2B9c TFA potently inhibits the interaction between PSD-95 and NMDA receptor subunits. The peptide inhibits NR2A and NR2B binding to PSD-95 with IC50 values of 0.5 µM and 8 µM, respectively. It inhibits PSD-95d2 with an EC50 of 6.7 nM. Tat-NR2B9c TFA also inhibits the interaction between neuronal nitric oxide synthase (nNOS) and PSD-95. By disrupting the PSD-95/NMDAR interaction, the peptide prevents the activation of NMDA-induced NADPH oxidase in neurons, thereby blocking the production of superoxide. This prevents excitotoxic signaling without blocking normal synaptic transmission, as the peptide does not interfere with NMDA receptor ion channel function. The peptide's neuroprotective efficacy has been demonstrated in various neuronal cell models of excitotoxicity and oxidative stress. |
| ln Vivo |
Tat-NR2B9c (10 nmol/g, iv) did not affect infarct volume at 3 nmol/g, but it did diminish it with C57BL/6 nozzles [3].
In vivo studies of Tat-NR2B9c TFA have demonstrated significant neuroprotective efficacy in animal models of stroke and ischemia. The peptide reduces neuronal injury and infarct volume in the acute phase after stroke by blocking the production of superoxide. In rodent models of middle cerebral artery occlusion (MCAO), Tat-NR2B9c TFA administered intravenously or intraperitoneally after the onset of ischemia reduces infarct volume and improves neurological outcomes. The peptide also exhibits antiepileptic effects. In vivo protocols typically involve administration of Tat-NR2B9c TFA at doses of 1-10 mg/kg, given intravenously or intraperitoneally, within 1-4 hours after ischemia onset. Endpoints include assessment of infarct volume, neurological scores, neuronal survival, and oxidative stress markers. The peptide's neuroprotective efficacy has been validated in multiple preclinical studies, supporting its potential as a therapeutic agent for stroke and other excitotoxic conditions. |
| Enzyme Assay |
For PSD-95 binding assays, the affinity of Tat-NR2B9c TFA for PSD-95 is measured using surface plasmon resonance (SPR) or fluorescence polarization. Purified PSD-95 PDZ domains (PDZ1-2 or PDZ2) are immobilized on a sensor chip, and varying concentrations of the peptide (0.001-100 µM) are injected over the chip surface. Binding kinetics (ka, kd) and affinity (KD) are calculated. For competition assays, the ability of the peptide to disrupt the interaction between PSD-95 and NR2B C-terminal peptides is assessed. Biotinylated NR2B peptides are immobilized on streptavidin-coated plates, and PSD-95 PDZ domains are added in the presence of varying concentrations of Tat-NR2B9c TFA. Bound PSD-95 is detected by ELISA using anti-PSD-95 antibodies. For nNOS/PSD-95 interaction assays, similar competition ELISA or pull-down assays are performed using purified nNOS and PSD-95 proteins. IC50 values are calculated from dose-response curves. For NADPH oxidase activity assays, neuronal cells are treated with NMDA in the presence or absence of the peptide, and superoxide production is measured using fluorescent probes (e.g., dihydroethidium) or lucigenin-enhanced chemiluminescence.
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| Cell Assay |
For in vitro neuroprotection studies, primary cortical or hippocampal neurons are cultured from embryonic or postnatal rodents in Neurobasal medium with B-27 supplement and glutamine. Neurons are seeded in 96-well or 24-well plates at densities of 1-5 × 10⁵ cells/well and cultured for 7-14 days in vitro (DIV). Tat-NR2B9c TFA is dissolved in sterile water or PBS and diluted in culture medium to final concentrations (typically 0.001-10 µM). For excitotoxicity assays, neurons are treated with the peptide for 30-60 minutes, then exposed to NMDA (10-100 µM) or glutamate (10-100 µM) for 5-30 minutes, followed by 24-hour recovery. Cell viability is assessed by LDH release, MTT, or calcein-AM staining. Apoptosis is measured by caspase-3/7 activity and TUNEL staining. Superoxide production is measured using dihydroethidium. For oxygen-glucose deprivation (OGD) models, neurons are subjected to OGD for 1-2 hours, followed by reoxygenation, and the peptide is added during OGD or at reperfusion. For Western blot analysis, neurons are lysed and analyzed for PSD-95, nNOS, and signaling proteins.
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| Animal Protocol |
For in vivo stroke studies, adult male rats or mice (8-12 weeks old) are used. The middle cerebral artery occlusion (MCAO) model is performed by inserting a silicone-coated filament into the internal carotid artery to occlude the MCA for 60-90 minutes, followed by reperfusion. Tat-NR2B9c TFA is dissolved in sterile saline and administered intravenously or intraperitoneally at doses of 1-10 mg/kg, typically as a bolus injection within 1-4 hours after the onset of ischemia. Some protocols use a single dose, while others use repeated dosing (e.g., at 0, 4, and 24 hours). At 24-72 hours after reperfusion, animals are euthanized, and brains are collected for infarct volume measurement using TTC staining. Neurological deficits are assessed using the modified neurological severity score (mNSS), corner test, or rotarod test. Oxidative stress markers (e.g., superoxide, MDA) and neuronal survival (NeuN staining) are assessed in brain sections. For pharmacokinetic studies, blood and brain samples are collected at various time points for peptide quantification by ELISA or LC-MS.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Tat-NR2B9c TFA indicate a relatively short half-life in plasma, which is typical for peptide therapeutics. The peptide is administered intravenously or intraperitoneally, with a plasma half-life of approximately 15-30 minutes in rodents. The peptide is distributed to the brain, where it exerts its neuroprotective effects. Its metabolism involves proteolytic cleavage by serum and tissue peptidases. The TFA (trifluoroacetate) salt form improves the peptide's solubility and stability. For in vivo studies, the peptide is typically administered as a bolus injection or by continuous infusion. The pharmacokinetic profile supports its use in acute conditions such as stroke, where rapid onset of action is critical.
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| Toxicity/Toxicokinetics |
Toxicological data for Tat-NR2B9c TFA are limited, as the peptide is used as a research tool. In preclinical studies, the peptide has been shown to be well-tolerated at neuroprotective doses (1-10 mg/kg), with no significant toxicity or adverse effects reported. The peptide's mechanism of action—disrupting PSD-95/NMDAR interaction without blocking normal synaptic transmission—is designed to provide neuroprotection without the side effects associated with NMDA receptor antagonists. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research peptides, appropriate safety precautions should be taken when handling Tat-NR2B9c TFA, including the use of personal protective equipment.
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| References |
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| Additional Infomation |
Na 1 is being studied in the clinical trial NCT00728182 (evaluating the neuroprotective effect in aneurysm embolization therapy).
Tat-NR2B9c TFA (NA-1) is a 20-amino acid peptide inhibitor of postsynaptic density-95 (PSD-95) with potent neuroprotective efficacy. It disrupts the interaction between PSD-95 and NMDA receptor subunits, preventing excitotoxic signaling without blocking normal synaptic transmission. The peptide inhibits NR2A and NR2B binding to PSD-95 with IC50 values of 0.5 µM and 8 µM, respectively, and inhibits nNOS/PSD-95 interaction. Tat-NR2B9c TFA prevents NMDA-induced NADPH oxidase activation and superoxide production, reducing ischemic injury after stroke. The peptide has been studied in stroke and ischemia models and exhibits antiepileptic effects. Tat-NR2B9c TFA is widely used in neuroprotection research and is strictly for research use only. |
| Molecular Formula |
C107H189F3N42O32
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|---|---|
| Molecular Weight |
2632.90299105644
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| Exact Mass |
2518.451
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| CAS # |
1834571-04-8
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| Related CAS # |
Tat-NR2B9c;500992-11-0
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| PubChem CID |
44568939
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| Appearance |
White to off-white solid powder
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| LogP |
-19.3
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| Hydrogen Bond Donor Count |
49
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| Hydrogen Bond Acceptor Count |
40
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| Rotatable Bond Count |
99
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| Heavy Atom Count |
177
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| Complexity |
5380
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| Defined Atom Stereocenter Count |
20
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| SMILES |
C(F)(F)(F)C(=O)O.[C@H](CCCNC(N)=N)(C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@@H](N)CC1C=CC(O)=CC=1
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| InChi Key |
XWQVQFBTSBCKLI-FKXNDIMNSA-N
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| InChi Code |
InChI=1S/C105H188N42O30/c1-7-55(6)80(98(175)140-69(34-36-77(154)155)92(169)143-72(50-148)95(172)142-71(48-78(156)157)94(171)146-79(54(4)5)99(176)177)147-97(174)74(52-150)145-96(173)73(51-149)144-93(170)70(46-53(2)3)141-90(167)62(22-10-13-39-108)133-85(162)63(24-15-41-124-101(113)114)135-87(164)65(26-17-43-126-103(117)118)136-88(165)66(27-18-44-127-104(119)120)138-91(168)68(33-35-75(110)152)139-89(166)67(28-19-45-128-105(121)122)137-86(163)64(25-16-42-125-102(115)116)134-84(161)61(21-9-12-38-107)132-83(160)60(20-8-11-37-106)131-82(159)59(23-14-40-123-100(111)112)130-76(153)49-129-81(158)58(109)47-56-29-31-57(151)32-30-56/h29-32,53-55,58-74,79-80,148-151H,7-28,33-52,106-109H2,1-6H3,(H2,110,152)(H,129,158)(H,130,153)(H,131,159)(H,132,160)(H,133,162)(H,134,161)(H,135,164)(H,136,165)(H,137,163)(H,138,168)(H,139,166)(H,140,175)(H,141,167)(H,142,172)(H,143,169)(H,144,170)(H,145,173)(H,146,171)(H,147,174)(H,154,155)(H,156,157)(H,176,177)(H4,111,112,123)(H4,113,114,124)(H4,115,116,125)(H4,117,118,126)(H4,119,120,127)(H4,121,122,128)/t55-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,74-,79-,80-/m0/s1
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| Chemical Name |
(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic 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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ≥ 50 mg/mL (~18.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (37.98 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3798 mL | 1.8990 mL | 3.7981 mL | |
| 5 mM | 0.0760 mL | 0.3798 mL | 0.7596 mL | |
| 10 mM | 0.0380 mL | 0.1899 mL | 0.3798 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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