1. Neuronal Signaling Protein Tyrosine Kinase/RTK
  2. Trk Receptor
  3. NSI-189 phosphate

NSI-189 is an orally active chemical entity with enhanced neurogenic activity. NSI-189 up-regulates neurogenic factors such as BDNF (brain derived-neurotrophic factor) and SCF. NSI-189 exhibits anti-depressant effect. NSI-189 enhances synaptic plasticity and reduces cognitive dysfunction. NSI-189 holds potential for psychiatric disorder research.

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NSI-189 phosphate Chemical Structure

NSI-189 phosphate Chemical Structure

CAS No. : 1270138-41-4

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Based on 1 publication(s) in Google Scholar

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Description

NSI-189 is an orally active chemical entity with enhanced neurogenic activity. NSI-189 up-regulates neurogenic factors such as BDNF (brain derived-neurotrophic factor) and SCF. NSI-189 exhibits anti-depressant effect. NSI-189 enhances synaptic plasticity and reduces cognitive dysfunction. NSI-189 holds potential for psychiatric disorder research[1][2][3].

In Vitro

NSI-189 enhances cell proliferation and neurogenesis in primary rat neurons (hippocampus) cells[2].
NSI-189 significantly attenuates OGD (oxygen glucose deprivation)-mediated hippocampal cell death and increases Ki67 and MAP2 expression[2].
NSI-189 up-regulates VEGF, GDNF, BDNF, SCF, BDNF and SCF levels in the hippocampal cells[2].
NSI-189 (1.0-3.0 μM, 24 h) augments neurite outgrowth and mitochondrial function in adult rat DRG (Dorsal root ganglia) sensory neurons[3].

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

Cell Viability Assay[3]

Cell Line: adult rat DRG sensory neurons cells
Concentration: 1.0-3.0 μM
Incubation Time: 24 h
Result: Significantly increased 24 h total neurite outgrowth in neurons from normal or diabetic rats.
In Vivo

NSI-189 (30 mg/kg, p.o., at 6 h after stroke, daily, 12 weeks) promotes behavioral recovery in stroke model rats[2].
NSI-189 (10 mg/kg, p.o., daily, 16 weeks) prevents PNS (peripheral nervous system) and CNS (central nervous system) neuropathy in type 1 diabetic mice[3].
NSI-189 (30 mg/kg, p.o., daily, 26 weeks) prevents peripheral neuropathy and ameliorates CNS and PNS neuropathy indb/db mice[3].

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

Animal Model: Adult Sprague-Dawley, male rats, 250 g, received experimental stroke surgery using the middle cerebral artery occlusion (MCAo) model[2].
Dosage: 30 mg/kg
Administration: p.o., at 6 h after stroke, daily, 12 weeks
Result: Promoted robust behavioral effects at acute stage, which remained stable over chronic period.
Stroke animals displayed significant amelioration of stroke-induced motor and neurological deficits.
Animal Model: Adult female Swiss Webster mice, adult male C57/BLKS/J and C57BLKSjBKS.Cg-Dock7m+/+ Leprdb/J (also called db/db) mice and adult male Sprague-Dawley rats. Type 1 diabetes was induced by injection of STZ (streptozotocin) (HY-13753) (90 mg/kg). Type 2 diabetes was modeled using db/db mice[3].
Dosage: 10 mg/kg (Female STZ-diabetic), 30 mg/kg (db/db mice, male control)
Administration: p.o., daily, 16 weeks (Female STZ-diabetic), 26 weeks (db/db mice, male control)
Result: Significantly protected long-term memory and attenuated reductions in the volume of the CA1 and DG regions in type 1 diabetic mice.
Significantly prevented or attenuated all deficits, such as paw tactile allodynia, paw heat hypoalgesia, reduced paw intraepidermal nerve fiber (IENF) density, and reduced corneal nerve density in the subbasal nerve plexus in type 1 diabetic mice.
Accelerated decline in nonfasted blood glucose of db/db mice in the terminal stages of the study.
Prevented loss of CA1 volume and increased BrdU-positive cell number in db/db mice.
Promoted a significant increase in corneal nerve density in the type2 diabetic mice.
Molecular Weight

464.49

Formula

C22H33N4O5P

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(N1CCN(CC1)CC2=CC=CC=C2)C3=CC=CN=C3NCCC(C)C.O=P(O)(O)O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (53.82 mM; Need ultrasonic; 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 2.1529 mL 10.7645 mL 21.5290 mL
5 mM 0.4306 mL 2.1529 mL 4.3058 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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (5.38 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (5.38 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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mg/kg

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(per animal)

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Dosing volume
(per animal)

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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+
%
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.1529 mL 10.7645 mL 21.5290 mL 53.8225 mL
5 mM 0.4306 mL 2.1529 mL 4.3058 mL 10.7645 mL
10 mM 0.2153 mL 1.0764 mL 2.1529 mL 5.3822 mL
15 mM 0.1435 mL 0.7176 mL 1.4353 mL 3.5882 mL
20 mM 0.1076 mL 0.5382 mL 1.0764 mL 2.6911 mL
25 mM 0.0861 mL 0.4306 mL 0.8612 mL 2.1529 mL
30 mM 0.0718 mL 0.3588 mL 0.7176 mL 1.7941 mL
40 mM 0.0538 mL 0.2691 mL 0.5382 mL 1.3456 mL
50 mM 0.0431 mL 0.2153 mL 0.4306 mL 1.0764 mL
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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NSI-189 phosphate
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HY-13999A1
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