| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
AA147 is an ATF6 simulator. It acts as a prodrug that preferentially triggers ATF6 signaling through a mechanism involving localized metabolic activation and selective covalent modification of ER resident proteins regulate ATF6 activity.
| ln Vitro |
Reactive oxygen species (ROS)-related damage is lessened by AA147 (20-0.078 μM (halved); 6 or 16 hours) in HT22 cells, preventing oxidative toxicity caused by valley induction [1]. AA147 (10 μM; 16 h) in HT22 AA147 (10 μM; 16 h) covalently alters KEAP1 in HT22 cells to encourage NRF2 activation [1]. AA147 recognizes ATF6 activation and upregulates phosphorylated cofilin in BPAEC (5, 10, 15 μM; 4, 8, 16, 24, 48 hours)[2]. In BPAEC, AA147 (10 μM; 24 hours) lessens the breakdown of the endothelium barrier caused by LPS [2].
|
|---|---|
| ln Vivo |
By activating ATF6, AA147 (intrathecal injection; single anesthetic for three days) can stimulate distal motor neuron expression, cut motor neuron neuroprotection, and rebalance XBP1 expression in severe SMA specimens [3].
|
| Cell Assay |
cell viability assay [1]
Cell Types: HT22 cell Tested Concentrations: 0.078, 0.156, 0.312, 0.625, 1.25, 2.5, 5, 10, 20 μM Incubation Duration: 6 or 16 h (pre-incubation) Experimental Results: demonstrated 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). diminished ROS accumulation in cells when pre-incubation of 16 h. Cell viability assay[1] Cell Types: HT22 Cell Tested Concentrations: 10 μM Incubation Duration: 16 hrs (hours) Experimental Results: The expression of genes related to antioxidant activity was Dramatically increased in the neuronal model, including prolactin and glutathione transferase. NRF2 is activated through a mechanism involving metabolic activation and covalent KEAP1 protein modification. Cell viability assay[2] Cell Types: BPAEC Tested Concentrations: 5, 10 μM Incubation Duration: 135 hrs (hours) Experimental Results: ATF6 activation reduces cell permeabi |
| References |
[1]. Rosarda JD, et al. Metabolically Activated Proteostasis Regulators Protect against Glutamate Toxicity by Activating NRF2. ACS Chem Biol. 2021 Dec 17;16(12):2852-2863.
[2]. Kubra KT, et al. Activating transcription factor 6 protects against endothelial barrier dysfunction. Cell Signal. 2022 Aug 4;99:110432. [3]. D'Amico D, et al. Activating ATF6 in spinal muscular atrophy promotes SMN expression and motor neuron survival through the IRE1α-XBP1 pathway. Neuropathol Appl Neurobiol. 2022 Aug;48(5):e12816. [4]. Christina COOLEY, et al. Regulators of the endoplasmic reticulum proteostasis network. WO2017117430A1. |
| Molecular Formula |
C16H17NO2
|
|---|---|
| Molecular Weight |
255.32
|
| Exact Mass |
255.1259
|
| CAS # |
393121-74-9
|
| SMILES |
O=C(CCC1C=CC=CC=1)NC1C(=CC=C(C)C=1)O
|
| Synonyms |
ATF6 activator 147 ATF6-activator 147 ATF6 activator-147
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~195.84 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (19.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 50.0 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: 5 mg/mL (19.58 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 50.0 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 | 3.9167 mL | 19.5833 mL | 39.1665 mL | |
| 5 mM | 0.7833 mL | 3.9167 mL | 7.8333 mL | |
| 10 mM | 0.3917 mL | 1.9583 mL | 3.9167 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
