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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.
Physicochemical Properties
| Molecular Formula | C16H17NO2 |
| Molecular Weight | 255.311684370041 |
| Exact Mass | 255.1259 |
| CAS # | 393121-74-9 |
| PubChem CID | 882909 |
| Appearance | Light brown to brown solid powder |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 19 |
| Complexity | 287 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(CCC1C=CC=CC=1)NC1C(=CC=C(C)C=1)O |
| Synonyms | ATF6 activator 147 ATF6-activator 147 ATF6 activator-147 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological 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]. Metabolically Activated Proteostasis Regulators Protect against Glutamate Toxicity by Activating NRF2. ACS Chem Biol. 2021 Dec 17;16(12):2852-2863. [2]. Activating transcription factor 6 protects against endothelial barrier dysfunction. Cell Signal. 2022 Aug 4;99:110432. [3]. 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]. Regulators of the endoplasmic reticulum proteostasis network. WO2017117430A1. |
Solubility Data
| 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 | 3.9168 mL | 19.5840 mL | 39.1681 mL | |
| 5 mM | 0.7834 mL | 3.9168 mL | 7.8336 mL | |
| 10 mM | 0.3917 mL | 1.9584 mL | 3.9168 mL |