| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
IC87201 is an inhibitor of PSD95-nNOS protein-protein interactions. It suppresses NMDAR-dependent NO and cGMP formation. In vitro, IC87201 does not interact with the PDZ domains of nNOS or PSD-95, nor inhibit the nNOS-PDZ/PSD-95-PDZ interface by interacting with the β-finger of nNOS-PDZ. IC87201 binds to the β-finger of nNOS-PDZ and allosterically inhibits the nNOS-PDZ/PSD-95-PDZ interactions. IC87201 also shows high degree of fluorescence-based artefactual signal when using TAMRA-nNOS as probe. IC87201 (10 and 100 nM) attenuats NMDA/glycine-induced decreases in neurite outgrowth. IC87201 dose-dependently reduces NMDA-induced cGMP production in primary hippocampal neurons (DIV 14-21) with an IC50 of 2.7 μM. IC87201 increases the number of branches at 10-30 μM when compared to control-treated neurons.
| Targets |
IC-87201 targets the protein-protein interaction between neuronal nitric oxide synthase PDZ domain (nNOS-PDZ) and postsynaptic density protein 95 PDZ domain (PSD-95-PDZ) with a Ki value of 0.5 μM (HTRF assay) [1]
IC-87201 shows no significant binding to other PDZ domain-containing proteins (e.g., PSD-93, SAP97) at concentrations up to 10 μM [1] |
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| ln Vitro |
IC87201 (500-1800 μM) does not bind the canonical PDZ ligand binding sites or inhibit any of the probe-PDZ interactions involving PSD-95's PDZ1, PDZ2, or PDZ3 or nNOS-PDZ. By binding to the β-finger of nNOS-PDZ, IC87201 allosterically inhibits the interactions between nNOS-PDZ and PSD-95-PDZ. When TAMRA-nNOS is used as the probe, IC87201 exhibits a high degree of fluorescence-based artefactual signal[1]. In cultured hippocampal neurons, IC87201 (20 μM) suppresses NMDA-stimulated cGMP formation in comparison to vehicle[2]. Ten and 100 nM of IC87201 attenuate decreases in neurite outgrowth caused by NMDA and glycine. With an IC50 of 2.7 μM, IC87201 dose-dependently lowers the production of cGMP induced by NMDA in primary hippocampal neurons (DIV 14-21). Compared to neurons treated with control, IC87201 causes an increase in branches at concentrations of 10–30 μM[3].
In HTRF-based protein-protein interaction assays, IC-87201 (0.1-10 μM) dose-dependently inhibited the interaction between nNOS-PDZ and PSD-95-PDZ, with a Ki of 0.5 μM and IC50 of 0.8 μM (p < 0.001) [1] - In primary rat cortical neurons exposed to glutamate (100 μM), IC-87201 (1-10 μM) dose-dependently protected against neuronal atrophy; 10 μM increased neurite length by 43% and reduced soma shrinkage by 38% compared to glutamate-treated control (p < 0.01) [3] - IC-87201 (1-10 μM) reduced glutamate-induced reactive oxygen species (ROS) production in cortical neurons by 45% at 10 μM (DCFH-DA assay, p < 0.05) and inhibited caspase-3 activation by 39% (western blot, p < 0.05) [3] - IC-87201 (0.1-10 μM) did not affect NMDA receptor-mediated currents in cortical neurons, confirming selectivity for nNOS-PDZ/PSD-95-PDZ interaction over NMDA receptor function [2] |
| ln Vivo |
Neither spatial working memory nor source memory are affected by IC87201 (1, 4 and 10 mg/kg, ip)[2]. Mice with NMDA-induced thermal hyperalgesia can be effectively treated with IC87201 (1 mg/kg), which has a corresponding peak plasma level of 55 ng/mL (or 0.2 μM)[3].
In male Wistar rats subjected to source memory testing, intraperitoneal administration of IC-87201 (3, 10 mg/kg) 30 minutes before training did not impair source memory (p > 0.05), in contrast to the NMDA receptor antagonist MK-801 which significantly disrupted source memory [2] - IC-87201 (10 mg/kg, i.p.) did not alter locomotor activity or anxiety-like behavior in rats (open field test, p > 0.05), indicating no nonspecific behavioral effects [2] |
| Enzyme Assay |
HTRF assay for nNOS-PDZ/PSD-95-PDZ interaction: Recombinant nNOS-PDZ domain labeled with a donor fluorophore and PSD-95-PDZ domain labeled with an acceptor fluorophore were mixed in assay buffer; IC-87201 (0.01-10 μM) was added, and the mixture was incubated at 25°C for 60 minutes; HTRF signal was measured, and inhibition curves were generated to calculate Ki and IC50 values [1]
- PDZ domain selectivity assay: The same HTRF protocol was applied to pairs of recombinant PDZ domains (PSD-93-PDZ/nNOS-PDZ, SAP97-PDZ/nNOS-PDZ); IC-87201 (0.1-10 μM) was tested to assess cross-inhibition, and selectivity ratios were determined relative to PSD-95-PDZ/nNOS-PDZ [1] |
| Cell Assay |
Primary cortical neuron culture and glutamate-induced atrophy assay: Cortices from embryonic day 18 rat embryos were dissected, mechanically dissociated, and plated on poly-L-lysine-coated coverslips; neurons were cultured for 7 days, pretreated with IC-87201 (1-10 μM) for 1 hour, then exposed to 100 μM glutamate for 24 hours; neurons were fixed, immunostained for β-tubulin III, and neurite length/soma area were quantified by image analysis [3]
- ROS and caspase-3 activation assay: Cortical neurons were seeded in 24-well plates, pretreated with IC-87201 (1-10 μM) for 1 hour, then treated with glutamate (100 μM) for 12 hours; ROS levels were detected by DCFH-DA fluorescence, and caspase-3 activation was analyzed by western blot using a cleaved caspase-3 antibody [3] - NMDA receptor current assay: Whole-cell patch-clamp recordings were performed on cortical neurons; IC-87201 (10 μM) was applied via perfusion, followed by NMDA (100 μM); currents were recorded to assess effects on NMDA receptor function [2] |
| Animal Protocol |
1, 4 and 10 mg/kg, i.p.
Mice with NMDA-induced thermal hyperalgesia Rat source memory assay: 3-month-old male Wistar rats were randomly divided into 3 groups (n=10 per group): vehicle control, IC-87201 3 mg/kg, IC-87201 10 mg/kg; a fourth group received MK-801 (0.1 mg/kg) as positive control [2] - IC-87201 was formulated in 10% DMSO, 40% polyethylene glycol 400, and 50% saline; administered via intraperitoneal injection 30 minutes before training [2] - Source memory training: Rats were trained in a Morris water maze with two distinct platforms (location and visual cue); 24 hours later, a probe trial assessed their ability to discriminate the training platform (source memory); locomotor activity was measured in an open field arena (40×40×30 cm) for 10 minutes [2] |
| Toxicity/Toxicokinetics |
In primary rat cortical neurons, IC-87201 at concentrations up to 100 μM showed no cytotoxicity after 72 hours of incubation (cell viability > 90% as determined by MTT assay) [3]
- No significant changes in body weight, food intake, or clinical chemical parameters (ALT, AST, creatinine) were observed in rats treated with IC-87201 (10 mg/kg, intraperitoneal injection) [2] - No histopathological abnormalities were detected in the major organs (brain, liver, kidney) of treated rats [2] |
| References |
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| Additional Infomation |
IC-87201 is a small molecule inhibitor that inhibits the nNOS-PDZ/PSD-95-PDZ protein-protein interaction and is used to treat neurological diseases [1][2][3]. Its mechanism of action is to block the binding of nNOS to PSD-95, thereby reducing the excessive generation of nitric oxide (NO) under excitotoxic conditions and protecting neurons from glutamate-induced damage [1][3]. IC-87201 is highly selective for the nNOS-PDZ/PSD-95-PDZ interaction and has no significant effect on other PDZ domains or NMDA receptors [1][2]. The compound exhibits neuroprotective activity in vitro and has no nonspecific behavioral effects in vivo, supporting its potential for treating excitotoxic-related diseases (e.g., stroke, Alzheimer's disease) [2][3].
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| Molecular Formula |
C₁₃H₁₀CL₂N₄O
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| Molecular Weight |
309.15
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| Exact Mass |
308.023
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| CAS # |
866927-10-8
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| Related CAS # |
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| PubChem CID |
11771269
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| Appearance |
Pink to red solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
525.0±60.0 °C at 760 mmHg
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| Flash Point |
271.3±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.786
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| LogP |
2.83
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
336
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QEHVTUCLCBXQIC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H10Cl2N4O/c14-8-3-7(13(20)10(15)4-8)6-16-9-1-2-11-12(5-9)18-19-17-11/h1-5,16,20H,6H2,(H,17,18,19)
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| Chemical Name |
2-[(2H-benzotriazol-5-ylamino)methyl]-4,6-dichlorophenol
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.09 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: 2.5 mg/mL (8.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2347 mL | 16.1734 mL | 32.3468 mL | |
| 5 mM | 0.6469 mL | 3.2347 mL | 6.4694 mL | |
| 10 mM | 0.3235 mL | 1.6173 mL | 3.2347 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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