1. Neuronal Signaling Stem Cell/Wnt
  2. γ-secretase
  3. NGP555

NGP555 is a γ-secretase modulator. NGP555 Lowers the Amyloid Biomarker Aβ42.

For research use only. We do not sell to patients.

NGP555 Chemical Structure

NGP555 Chemical Structure

CAS No. : 1304630-27-0

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
USD 264 In-stock
Solution
10 mM * 1 mL in DMSO USD 264 In-stock
Solid
1 mg USD 114 In-stock
5 mg USD 240 In-stock
10 mg USD 410 In-stock
25 mg USD 820 In-stock
50 mg USD 1400 In-stock
100 mg USD 2100 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 1 publication(s) in Google Scholar

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

NGP555 is a γ-secretase modulator. NGP555 Lowers the Amyloid Biomarker Aβ42[1].

IC50 & Target

γ-secretase[1]

Cellular Effect
Cell Line Type Value Description References
CHO IC50
10 nM
Compound: 1
Modulation of gamma-secretase in CHO cells expressing human APP695 assessed as inhibition of Abeta42 level after 20 hrs by FRET HTS assay
Modulation of gamma-secretase in CHO cells expressing human APP695 assessed as inhibition of Abeta42 level after 20 hrs by FRET HTS assay
[PMID: 27426299]
SH-SY5Y EC50
29 nM
Compound: 42
Modulation of gamma-secretase in human SH-SY5Y cells expressing human APP751 assessed as reduction in amyloid beta 42 production after 18 to 22 hrs by sandwich ELISA
Modulation of gamma-secretase in human SH-SY5Y cells expressing human APP751 assessed as reduction in amyloid beta 42 production after 18 to 22 hrs by sandwich ELISA
[PMID: 27007185]
In Vitro

NGP555 potently lowers Aβ42 in cell cultures (9 nM) while increasing shorter forms of Aβ[1].

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

In Vivo

NGP555 significantly lowers Aβ42 in the cerebrospinal fluid (CSF) at time points from 8 to10 hours post dose, panel B shows that reduction of Aβ cerebrospinal fluid (CSF) levels is significant at 3.75 mg/kg of NGP555 and above, and panel C shows an increase in Aβ38 levels at 15 mg/kg of NGP555 and above. When combining the reduction of Aβ42 with an increase in Aβ38, NGP555 is effective at raising CSF Aβ38/42 ratio at 1.87 mg/kg and above (panel D). NGP555-treated Tg mice show a significant protection from decline in performance with >65% less decline (P<0.005) when comparing the differential of Tg to non-Tg vehicle-treated mice. NGP555 also shows good oral bioavailability and is brain-penetrant with a brain:plasma ratio of ~0.93 in mice[1].

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

Clinical Trial
Molecular Weight

406.52

Formula

C23H23FN4S

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

CC1=CN(C2=CC=C(C3=CSC(NC4=CC(CC)=C(C)C=C4C)=N3)C=C2F)C=N1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 25 mg/mL (61.50 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 2.4599 mL 12.2995 mL 24.5990 mL
5 mM 0.4920 mL 2.4599 mL 4.9198 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
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Concentration
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Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

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Concentration (final)

C2

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Volume (final)

V2

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    40% PEG300    5% Tween-80    45% Saline

    Solubility: 2.5 mg/mL (6.15 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

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

    Solubility: ≥ 2.5 mg/mL (6.15 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:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
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).
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
Cell Assay
[1]

SH-SY5Y-APP cells, Tg2576 mixed brain cultures, or C57 mixed brain cultures are treated with various concentrations of NGP555 in triplicate wells, for 18 hours. Media is collected and analyzed for Aβ peptides using triplex ELISA (Aβ38 and Aβ42)[1].

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

Animal Administration
[1]

For CSF studies, Normal Sprague-Dawley male rats (250 to 300 g) are administered NGP555 in 80% PEG orally or vehicle only, n=10/group. Rats are dosed once-daily for a single-dose or 14 days of dosing. After the final dose, cerebrospinal fluid (CSF) samples are either collected at varying time points or a single time point post-last dose. Rats are deeply anesthetized with isoflurane, and CSF is collected from the cisterna magna. Samples are tested for Aβ level. For Y-maze study, transgenic mice (Tg2576 line expressing the APP-Swe mutation) and non-transgenic age-matched littermates (n=a minimum of 12/group) are treated with vehicle, NGP555 (25 mg/kg) once-daily for 30 consecutive days (starting at 5 months of age). At 6 months, mice are assessed on the Y-maze behavior test[1].

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

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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.4599 mL 12.2995 mL 24.5990 mL 61.4976 mL
5 mM 0.4920 mL 2.4599 mL 4.9198 mL 12.2995 mL
10 mM 0.2460 mL 1.2300 mL 2.4599 mL 6.1498 mL
15 mM 0.1640 mL 0.8200 mL 1.6399 mL 4.0998 mL
20 mM 0.1230 mL 0.6150 mL 1.2300 mL 3.0749 mL
25 mM 0.0984 mL 0.4920 mL 0.9840 mL 2.4599 mL
30 mM 0.0820 mL 0.4100 mL 0.8200 mL 2.0499 mL
40 mM 0.0615 mL 0.3075 mL 0.6150 mL 1.5374 mL
50 mM 0.0492 mL 0.2460 mL 0.4920 mL 1.2300 mL
60 mM 0.0410 mL 0.2050 mL 0.4100 mL 1.0250 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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NGP555
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