| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
The primary mechanism of NSI-189 involves the stimulation of neurogenesis in the hippocampus. It indirectly modulates BDNF (brain-derived neurotrophic factor) and SCF (stem cell factor). Additionally, NSI-189 has been reported to exhibit antiviral activity against SARS-CoV-2 and inhibitory effects on human HDAC6 enzyme. Its unique mechanism of action makes it a promising candidate for conditions related to hippocampal dysfunction.
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| ln Vitro |
In vitro, NSI-189 has been shown to stimulate neurogenesis of human hippocampus-derived neural stem cells. It enhances cell proliferation and neurogenesis in primary rat hippocampal neurons. At a concentration of 10 µM after 48 hours, it inhibits cytotoxicity in Caco-2 and VERO-6 cells with inhibition rates of 8.05% and -0.14%, respectively.
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| ln Vivo |
In vivo, NSI-189 stimulates neurogenesis in the murine hippocampus. It has been shown to increase the hippocampal volume of healthy adult mice by 20%. Oral administration of NSI-189 exhibits antidepressant effects and enhances synaptic plasticity in animal models.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays (non-cell-based) for NSI-189 typically involve radioligand binding or fluorescence polarization techniques to assess its interaction with potential targets like BDNF receptors or HDAC6. Competitive binding assays are performed using purified enzyme preparations or receptor proteins, with IC50 values determined through dose-response curves. While specific protocols for NSI-189 are not extensively detailed in public literature, standard biochemical assay formats using recombinant proteins and fluorescent or radioactive substrates are applicable.
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| Cell Assay |
In vitro cellular assays for NSI-189 commonly utilize human hippocampus-derived neural stem cells or primary rat hippocampal neurons to evaluate neurogenesis and cell proliferation. Cells are treated with varying concentrations of NSI-189, and neurogenesis is assessed via immunocytochemistry for neuronal markers (e.g., βIII-tubulin, NeuN) and proliferation markers (e.g., BrdU incorporation). Cytotoxicity is evaluated in Caco-2 and VERO-6 cells using standard cell viability assays such as MTT or CCK-8.
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| Animal Protocol |
In vivo animal studies for NSI-189 are conducted in murine models, where the compound is administered orally to assess its effects on hippocampal neurogenesis and volume. Adult healthy mice receive NSI-189 treatment, followed by histological analysis of hippocampal tissue to measure neurogenesis and volume changes. Behavioral tests, such as the forced swim test and tail suspension test, are used to evaluate antidepressant-like effects.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NSI-189 indicate it is orally active with good bioavailability. It is soluble in DMSO at concentrations up to 110 mg/mL. The compound is typically administered orally, and its distribution includes the central nervous system, given its effects on hippocampal neurogenesis. For storage, the powder should be kept at -20°C, and stock solutions should be stored at -80°C for up to 6 months or at -20°C for up to 1 month.
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| Toxicity/Toxicokinetics |
Toxicological information for NSI-189 is primarily derived from preclinical studies. It has demonstrated a favorable safety profile in animal models at therapeutic doses, with no severe adverse effects reported in available literature. The compound's safety for human use has not been established, as it is currently a research chemical not approved for clinical application. Standard toxicological assessments, including acute and repeated-dose toxicity studies, would be required for clinical development.
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| References | |
| Additional Infomation |
NSI-189 is an aromatic carboxylic acid and a pyridine monocarboxylic acid. NSI-189 is currently being investigated in the clinical trial NCT02695472 (NSI-189 study for the treatment of major depressive disorder).
NSI-189 is under investigation as a hippocampal neurogenesis stimulant and indirect BDNF modulator. It is also known as Amdiglurax and ALTO-100. Developed by Alto Neuroscience, it holds potential for the research of psychiatric disorders. It has not yet been approved by the FDA or other regulatory agencies for therapeutic use and remains an investigational compound for research purposes only. |
| Molecular Formula |
C22H30N4O
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|---|---|
| Molecular Weight |
366.4998
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| Exact Mass |
366.241
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| CAS # |
1270138-40-3
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| PubChem CID |
50922681
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
534.7±50.0 °C at 760 mmHg
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| Flash Point |
277.2±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.601
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| LogP |
4.13
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
442
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N1CCN(CC2=CC=CC=C2)CC1)C3=CC=CN=C3NCCC(C)C
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| InChi Key |
DYTOQURYRYYNOR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H30N4O/c1-18(2)10-12-24-21-20(9-6-11-23-21)22(27)26-15-13-25(14-16-26)17-19-7-4-3-5-8-19/h3-9,11,18H,10,12-17H2,1-2H3,(H,23,24)
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| Chemical Name |
(4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone
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| Synonyms |
NSI189; NSI 189; NSI-189
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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) |
DMSO : ~110 mg/mL (~300.14 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.75 mg/mL (7.50 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 27.5 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: ≥ 2.75 mg/mL (7.50 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 27.5 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: ≥ 2.75 mg/mL (7.50 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 | 2.7285 mL | 13.6426 mL | 27.2851 mL | |
| 5 mM | 0.5457 mL | 2.7285 mL | 5.4570 mL | |
| 10 mM | 0.2729 mL | 1.3643 mL | 2.7285 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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