2. Cell Cycle/DNA Damage NF-κB Metabolic Enzyme/Protease Immunology/Inflammation
  3. ATF6 Reactive Oxygen Species
  4. AA147

AA147 is a endoplasmic reticulum (ER) proteostasis regulator. AA147 promotes protection against oxidative damage in neuronal cells and prevents endothelial barrier dysfunction by activating ATF6 arm (selectively) of the unfolded protein response (UPR) and the NRF2 oxidative stress response. AA147 can rebalances XBP1s expression in vivo, and also induces survival motor neuron (SMN) expression and spinal motorneuron (MN) protection.

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AA147 Chemical Structure

AA147 Chemical Structure

CAS No. : 393121-74-9

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Based on 3 publication(s) in Google Scholar

AA147 Related Antibodies

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Description

AA147 is a endoplasmic reticulum (ER) proteostasis regulator. AA147 promotes protection against oxidative damage in neuronal cells and prevents endothelial barrier dysfunction by activating ATF6 arm (selectively) of the unfolded protein response (UPR) and the NRF2 oxidative stress response. AA147 can rebalances XBP1s expression in vivo, and also induces survival motor neuron (SMN) expression and spinal motorneuron (MN) protection[1][2][3][4].

In Vitro

AA147 (20-0.078 μM (dilution in half); 6 or 16 h) protects against glutamate-induced oxidative toxicity in HT22 cells by decreasing the reactive oxygen species (ROS)-associated damage[1].
AA147 (10 μM; 16 h) induces NRF2-dependent upregulation of oxidative stress response genes in HT22 cells[1].
AA147 (10 μM; 16 h) covalently modifies KEAP1 to promote NRF2 activation in HT22 cells[1].
AA147 (5, 10, 15 μM; 4, 8, 16, 24, 48 h) induces ATF6 activation and upregulates phosphorylation of cofilin in BPAEC[2].
AA147 (10 μM; 24 h) reduces LPS-induced endothelial barrier disruption in BPAEC[2].
AA147 (5, 10 μM; 135 h) enhances lung endothelial barrier integrity[2].

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

AA147 Related Antibodies

Cell Viability Assay[1]

Cell Line: HT22 cells
Concentration: 0.078, 0.156, 0.312, 0.625, 1.25, 2.5, 5, 10, 20 μM
Incubation Time: 6 or 16 h (pre-incubation)
Result: Showed dose-dependent increases in the viability of glutamate-treated HT22 cells when pretreated with AA147 for 6 or 16 h prior to the glutamate challenge (addition concurrently with the glutamate challenge did not improve the viability of glutamate-treated cells).
Reduced ROS accumulation in cells when pre-incubation of 16 h.

Cell Viability Assay[1]

Cell Line: HT22 cells
Concentration: 10 μM
Incubation Time: 16 h
Result: Significant increased the expression of genes associated with antioxidant activity in neuronal models, including prolactins and glutathione transferases.
Activated NRF2 through a mechanism involving metabolic activation and covalent KEAP1 protein modification.

Cell Viability Assay[2]

Cell Line: BPAEC
Concentration: 5, 10 μM
Incubation Time: 135 h
Result: Decreased permeability of cells by activation of ATF6.

Western Blot Analysis[2]

Cell Line: BPAEC
Concentration: 5, 10, 15 μM
Incubation Time: 4, 8, 16, 24, 48 h
Result: Significantly induced ATF6 activation and upregulated cofilin phosphorylation (in a concentration-dependent manner).

Western Blot Analysis[2]

Cell Line: BPAEC
Concentration: 10 μM
Incubation Time: 24 h
Result: Reduced LPS-induced cATF6 suppression (Fig.5A) and VE-cadherin phosphorylation.
Inhibited cofilin and MLC2 activation in the inflamed cells.
Inhibited LPS-induced hyperpermeability in BPAEC.
In Vivo

AA147 (intrathecal injection; single for 3 days) can rebalance XBP1s expression in severe SMA-like mice by activating ATF6, and also induce survival motor neuron expression and spinal motorneuron protection[3].

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

255.31

Formula

C16H17NO2
CAS No.
Appearance

Solid

Color

Light brown to brown

SMILES

O=C(NC1=CC(C)=CC=C1O)CCC2=CC=CC=C2
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 : 50 mg/mL (195.84 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 3.9168 mL 19.5840 mL 39.1681 mL
5 mM 0.7834 mL 3.9168 mL 7.8336 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)

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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    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 5 mg/mL (19.58 mM); Clear solution

    This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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% (20% SBE-β-CD in Saline)

    Solubility: 5 mg/mL (19.58 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 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 (50.0 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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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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).
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, 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 3.9168 mL 19.5840 mL 39.1681 mL 97.9202 mL
5 mM 0.7834 mL 3.9168 mL 7.8336 mL 19.5840 mL
10 mM 0.3917 mL 1.9584 mL 3.9168 mL 9.7920 mL
15 mM 0.2611 mL 1.3056 mL 2.6112 mL 6.5280 mL
20 mM 0.1958 mL 0.9792 mL 1.9584 mL 4.8960 mL
25 mM 0.1567 mL 0.7834 mL 1.5667 mL 3.9168 mL
30 mM 0.1306 mL 0.6528 mL 1.3056 mL 3.2640 mL
40 mM 0.0979 mL 0.4896 mL 0.9792 mL 2.4480 mL
50 mM 0.0783 mL 0.3917 mL 0.7834 mL 1.9584 mL
60 mM 0.0653 mL 0.3264 mL 0.6528 mL 1.6320 mL
80 mM 0.0490 mL 0.2448 mL 0.4896 mL 1.2240 mL
100 mM 0.0392 mL 0.1958 mL 0.3917 mL 0.9792 mL
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AA147 Related Classifications

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.

Keywords:

AA147393121-74-9AA 147AA-147ATF6Reactive Oxygen SpeciesActivating transcription factor 6neurodegenerative disordersROSNRF2BPAECSMAInhibitorinhibitorinhibit

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