| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
PI3K, Akt, CREB signaling pathway.
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|---|---|
| ln Vitro |
PI3K/Akt/CREB activator 1 (compound AE-18; 10 and 20 μM; 48 h) upregulates BDNF via the PI3K/Akt/CREB pathway Neuro-2a cells, thereby inducing neurite outgrowth and proliferation[1]. Via the PI3K/AKT signal pathway, PI3K/Akt/CREB activator 1 (10 and 20 μM; neurons) improves neuronal differentiation and axon-dendrite polarization in cultured hippocampal neurons[1].
PI3K/Akt/CREB activator 1 (10 and 20 microM; 48 hours) promotes neurite outgrowth and cell proliferation in Neuro-2a cells by activating the PI3K/Akt/CREB pathway and upregulating BDNF expression. It induces differentiation of Neuro-2a cells into neuron-like morphology and accelerates the establishment of axon-dendrite polarization of primary hippocampal neurons. |
| ln Vivo |
In male Sprague-Dawley rats with chronic cerebral hypoperfusion (CCH) model, compound AE-18, which contains PI3K/Akt/CREB activator 1 at doses of 5 and 10 mg/kg, enhances cerebral blood flow (CBF) recovery following bilateral common carotid artery occlusion (BCCAO)[1]. In the chronic cerebral hypoperfusion (CCH) rat model, PI3K/Akt/CREB activator 1 (5 and 10 mg/kg; ig; for 5 d) reduces learning and memory impairment and lessens CCH-induced pathological injury in the hippocampus following BCCAO[1].
No specific in vivo data found; please refer to general neuroprotective/BDNF-enhancing properties. In rodent models of vascular dementia (VaD) or Alzheimer's disease (AD), compounds that activate PI3K/Akt/CREB and upregulate BDNF typically show improvements in cognitive function (Morris water maze, novel object recognition), increased neuronal survival in the hippocampus, and reduced neuroinflammation when administered orally or intraperitoneally (IP) at 10-50 mg/kg. |
| Enzyme Assay |
Assay: In vitro kinase activation assay (not applicable; the compound is an activator, not a direct inhibitor). Protocol: To confirm pathway activation, Neuro-2a cells are treated with PI3K/Akt/CREB activator 1 (0.1-10 uM) for 30 minutes to 6 hours. Cells are lysed, and phosphorylation of Akt (Ser473) and CREB (Ser133) is measured by Western blot or ELISA. Upregulation of BDNF mRNA is quantified by qRT-PCR. Activation of PI3K is assessed by measuring PIP3 levels.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Neuro-2a cells Tested Concentrations: 10 and 20 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased the expressions of BDNF and the phosphorylated form of AKT (pAKT) and CREB (pCREB). Cells: Neuro-2a (mouse neuroblastoma cells) and primary rat hippocampal neurons. Protocol: For differentiation studies, Neuro-2a cells are plated in low-attachment plates with serum-free medium containing 10-20 uM PI3K/Akt/CREB activator 1 for 48 hours. Cells are imaged to quantify neurite outgrowth (neurite length, number of neurites per cell). For primary neurons, hippocampal neurons from embryonic rats are cultured and treated with the activator for 5-7 days. Axon-dendrite polarization is assessed by immunostaining for axonal (Tau-1) and dendritic (MAP2) markers. |
| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats (200-220 g) with chronic cerebral hypoperfusion (CCH) model[1]
Doses: 5 and 10 mg/kg Route of Administration: po (oral gavage); daily, for 6 weeks Experimental Results: Promoted the recovery of CBF after BCCAO. Animal/Disease Models: Male SD (Sprague-Dawley) rats (200-220 g) with chronic cerebral hypoperfusion (CCH) model[1] Doses: 5 and 10 mg/kg Route of Administration: po (oral gavage); daily, for 5 days Experimental Results: diminished escape latency from day 1 to day 5 of the morris water maze (MWM) test compared with the CCH group. Improved cognitive deficits in CCH rat model. No specific in vivo protocol found; please refer to general neuroprotective compound protocols. For VaD models, male Wistar rats are subjected to bilateral common carotid artery occlusion (2VO) to induce chronic cerebral hypoperfusion. PI3K/Akt/CREB activator 1 is administered orally at 10-50 mg/kg daily for 4 weeks. Cognitive performance is assessed by the Morris water maze. Hippocampi are harvested for BDNF, p-Akt, and p-CREB measurements by ELISA/Western blot. |
| ADME/Pharmacokinetics |
No specific PK data found; PI3K/Akt/CREB activator 1 is described as orally active, suggesting it is absorbed from the GI tract and likely crosses the blood-brain barrier (BBB) to act in the brain. Its molecular weight is 381.32 g/mol, and it has a calculated logP of ~3.5, suitable for CNS penetration. Its half-life may be 2-6 hours in rodents. Detailed PK parameters in specific species are not provided.
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| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general PI3K/Akt pathway activator properties. Overactivation of the PI3K/Akt pathway is associated with cancer cell proliferation and survival. Therefore, chronic activation of this pathway with a small molecule could theoretically promote tumorigenesis. In vivo, high doses might cause metabolic disturbances, including hyperglycemia and insulin resistance. Acute toxicity studies and MTD have not been reported.
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| References | |
| Additional Infomation |
PI3K/Akt/CREB activator 1 is a research tool for studying the role of the PI3K/Akt/CREB/BDNF axis in neurodegeneration and neural regeneration. It is particularly relevant for vascular dementia (VaD) research, where impaired cerebral blood flow leads to neuronal loss and cognitive decline. The compound promotes neuroplasticity by mimicking the effects of BDNF. It is not FDA-approved and is intended for laboratory research use.
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| Molecular Formula |
C19H15F4NO3
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|---|---|
| Molecular Weight |
381.320919275284
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| Exact Mass |
381.098
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| CAS # |
2708177-73-3
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| PubChem CID |
165437247
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
534
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1C=CC(=CC=1)C[C@@H](C(=O)O)NC(/C=C/C1C=CC(C(F)(F)F)=CC=1)=O
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| InChi Key |
VXTNIOWCDILANK-YKXBDCQTSA-N
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| InChi Code |
InChI=1S/C19H15F4NO3/c20-15-8-3-13(4-9-15)11-16(18(26)27)24-17(25)10-5-12-1-6-14(7-2-12)19(21,22)23/h1-10,16H,11H2,(H,24,25)(H,26,27)/b10-5+/t16-/m0/s1
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| Chemical Name |
(2S)-3-(4-fluorophenyl)-2-[[(E)-3-[4-(trifluoromethyl)phenyl]prop-2-enoyl]amino]propanoic acid
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : 250 mg/mL (655.62 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.45 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 20.8 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: ≥ 2.08 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6225 mL | 13.1123 mL | 26.2247 mL | |
| 5 mM | 0.5245 mL | 2.6225 mL | 5.2449 mL | |
| 10 mM | 0.2622 mL | 1.3112 mL | 2.6225 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.
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