Levacetylleucine

Melting Point: 187-190°C(lit.)

Storage temp: Sealed in dry, Room Temperature

Solubility: DMSO (Slightly), Ethanol (Slightly), Water (Slightly, Heated)

Form: Crystalline Powder

Color: White

1. Cell Experiment

Solubility in DMSO : 100 mg/mL (577.33 mM; ultrasonic co-solubilization; Hygroscopic DMSO has a significant effect on the solubility of the product, use freshly opened DMSO)

Preparing Stock Solutions：

Please choose the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; Once prepared into a solution, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and duration of stock solution: -80°C, 2 years; -20°C, 1 year。 Use within 2 years when stored at -80°C, and within 1 year when stored at -20°C.

2. Animal Control

Choose the appropriate dissolution protocol based on your experimental animal and mode of administration.

For the following dissolution schemes, please prepare the clarified stock solution according to the in vitro method, and then add the co-solvent in turn:

- In order to ensure the reliability of the experimental results, the clarified stock solution can be properly stored according to the storage conditions; It is recommended that you use the working solution for in vivo experiments and use it on the same day;

The percentages shown before the following solvents are the proportion of the volume of that solvent in your final solution; If precipitation and precipitation occur during the preparation process, it can be dissolved by heating and/or ultrasound.

Option 1

Add each solvent in order:  10% DMSO ,   40% PEG300 ,  5% Tween-80, 45% Saline.

Solubility: ≥ 2.5 mg/mL (14.43 mM); Clear Solution

A clarified solution of ≥ 2.5 mg/mL (saturation unknown) is obtained for this protocol.

For example, take 1 mL of working solution and add 100 μL of 25.0 mg/mL of clarified DMSO stock solution to 400 μL of PEG300 and mix well. Add 50 μL of Tween-80 to the above system and mix well; Then proceed with 450 μL of normal saline to 1 mL.

Preparation of normal saline: 0.9 g of sodium chloride dissolved in ddH₂O and fixed to 100 mL can obtain a clear and transparent normal saline solution.

Option 2

add each solvent in order: 10% DMSO;90% (20% SBE-β-CD in Saline).

Solubility:  ≥ 2.5 mg/mL (14.43 mM); Clear Solution.

A clarified solution of ≥ 2.5 mg/mL (saturation unknown) is obtained for this protocol.

For example, take 1 mL of working solution and add 100 μL of 25.0 mg/mL of clarified DMSO stock solution to 900 μL of 20% SBE-β-CD saline aqueous and mix well.

2 g of SBE-β-CD (sulfonbutyl ether β-cyclodextrin) powder is set in 10 mL of normal saline and completely dissolved until clear.

Option 3

Add each solvent in order: 10% DMSO , 90% Corn Oil.

Solubility:  ≥ 2.5 mg/mL (14.43 mM); Clear solution

A clarified solution of ≥ 2.5 mg/mL (saturation unknown) is available for this protocol, as appropriate for animal experiments with experimental cycles of more than half a month.

For example, 100 μL of 25.0 mg/mL of clarified DMSO stock solution is added to 900 μL of corn oil and mixed well.

The pharmacodynamics of levacetylleucine are not well characterized. There does not appear to be a relationship between increasing levacetylleucine exposure and clinical efficacy.

Following oral administration, levacetylleucine is taken up via ubiquitously expressed monocarboxylate transporters and distributed to all body tissues.It enters enzyme-controlled pathways that correct metabolic dysfunction and improves adenosine triphosphate (ATP) energy production.The normalization of energy metabolism ameliorates mitochondrial and lysosomal dysfunction and leads to a reduction in the storage of unesterified cholesterol and sphingolipids.Levacetylleucine has also been shown to normalize neuronal membrane potentials in a guinea pig model, thereby improving cellular signaling processes and restoring and protecting neuronal circuits. The specific molecular target of levacetylleucine in the context of Niemann-Pick disease type C (NPC) is unknown.