PI3K/Akt/CREB activator 1 (compound AE-18) is an orally bioavailable activator of PI3K/Akt/CREB. PI3K/Akt/CREB activator 1 upregulates brain-derived neurotrophic factor through the PI3K/Akt/CREB pathway, promotes neuronal proliferation, induces the differentiation of Neuro-2a cells into neuron-like morphology, and accelerates axons and dendrites of hippocampal primary neurons. The establishment of polarization. PI3K/Akt/CREB activator 1 may be utilized in the study of vascular dementia (VaD).

Physicochemical Properties

Molecular Formula	C19H15F4NO3
Molecular Weight	381.320919275284
Exact Mass	381.098
CAS #	2708177-73-3
PubChem CID	165437247
Appearance	White to off-white solid powder
LogP	4.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	27
Complexity	534
Defined Atom Stereocenter Count	1
SMILES	FC1C=CC(=CC=1)C[C@@H](C(=O)O)NC(/C=C/C1C=CC(C(F)(F)F)=CC=1)=O
InChi Key	VXTNIOWCDILANK-YKXBDCQTSA-N
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
Chemical Name	(2S)-3-(4-fluorophenyl)-2-[[(E)-3-[4-(trifluoromethyl)phenyl]prop-2-enoyl]amino]propanoic acid
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	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].
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].
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).
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.
References	[1]. Protective Effects of 4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine Acid against Chronic Cerebral Hypoperfusion Injury through Promoting Brain-Derived Neurotrophic Factor-Mediated Neurogenesis. ACS Chem Neurosci. 2022 Oct 16.

Solubility Data

Solubility (In Vitro)

DMSO : 250 mg/mL (655.62 mM)

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.