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gamma-Methylleucine

Alias: Neopentylglycine; gamma-Methyl-L-leucine; gamma-Methylleucine
Cat No.:V21500 Purity: ≥98%
4-Methyl-L-leucine is a glycine analogue.
gamma-Methylleucine
gamma-Methylleucine Chemical Structure CAS No.: 57224-50-7
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
500mg
1g
Other Sizes
Official Supplier of:
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Product Description
4-Methyl-L-leucine is a glycine analogue.
gamma-Methylleucine (CAS#: 57224-50-7) is a leucine derivative, also known as 4-methyl-L-leucine or 3-tert-butyl-L-alanine. It is a glycine analogue that has been utilized commercially as an ergot supplement. The compound plays a crucial role in biochemical reactions, particularly in the regulation of protein synthesis and metabolism. gamma-Methylleucine has been shown to have various biological effects on cell function and signal transduction. It can modulate the activity of the mammalian target of rapamycin (mTOR) pathway, which plays a crucial role in protein synthesis and cell growth.
Biological Activity I Assay Protocols (From Reference)
Targets
gamma-Methylleucine interacts with several enzymes and proteins, including the mechanistic target of rapamycin complex 1 (mTORC1), which is a key regulator of cell growth and metabolism. The compound also affects endothelin-1 (ET-1) biological activity, resulting in loss or significant decrease of ET-1 activity while retaining high affinity for ETA (IC50 = 0.42-0.70 nM) and ETB (IC50 = 0.17-0.43 nM) receptors. It improves peptide binding affinity to the Y2 receptor and enhances anorectic activity in lean mice. The compound modulates the mTOR pathway, affecting protein synthesis and cell growth.
ln Vitro
As ergot supplements, amino acids and their derivatives have been utilized commercially. They affect anabolic hormone secretion, fuel supply during exercise, cognitive function during stressful tasks, and the avoidance of muscular injury brought on by exercise. They are regarded as advantageous dietary additives [1].
In vitro, gamma-Methylleucine improves the binding affinity of peptides to the Y2 receptor. It results in loss or significant decrease of endothelin-1 biological activity while maintaining high affinity for ETA and ETB receptors. The compound modulates mTOR pathway activity, affecting protein synthesis and cell growth in cultured cells. As an amino acid derivative, it affects anabolic hormone secretion, fuel supply during exercise, cognitive function during stressful tasks, and prevention of muscular injury. These effects have been demonstrated in various in vitro systems.
ln Vivo
In vivo, gamma-Methylleucine enhances the anorectic activity of peptides in lean mice. Amino acids and their derivatives, including gamma-methylleucine, have been utilized commercially as ergot supplements affecting anabolic hormone secretion, fuel supply during exercise, cognitive function, and prevention of exercise-induced muscle injury. The compound's effects on mTOR signaling suggest potential roles in metabolic regulation and muscle physiology. Its interactions with endothelin receptors may have implications for cardiovascular function.
Enzyme Assay
In vitro receptor binding assays for gamma-Methylleucine typically involve radioligand binding studies to determine its affinity for ETA and ETB receptors. Membranes from cells expressing these receptors are incubated with radiolabeled ligands and varying concentrations of the compound. Binding affinity (IC50 values) is determined from competition binding curves. Y2 receptor binding assays are performed using similar approaches. These cell-free assays provide quantitative data on the compound's receptor interactions. Functional assays may also be used to assess the compound's effects on receptor-mediated signaling.
Cell Assay
In vitro cell-based assays for gamma-Methylleucine involve treating cells with the compound to assess its effects on mTOR signaling and protein synthesis. Cells are cultured with varying concentrations of the compound, and mTOR pathway activity is measured by assessing phosphorylation of downstream targets such as S6K1 and 4E-BP1. Protein synthesis rates are measured using labeled amino acid incorporation. Cell proliferation and viability are assessed using standard colorimetric assays. The compound's effects on anabolic hormone secretion and cellular metabolism can be studied in appropriate cell culture models.
Animal Protocol
In vivo animal experiments for gamma-Methylleucine have been conducted in lean mice to assess its effects on anorectic activity. The compound is typically administered orally or via injection, and its effects on food intake and body weight are monitored. Studies on exercise performance and muscle recovery have also been conducted in animal models. The compound's effects on endothelin receptor signaling may be evaluated in cardiovascular models. Doses and administration routes vary depending on the specific experimental objectives.
ADME/Pharmacokinetics
gamma-Methylleucine is a leucine derivative with a molecular weight consistent with amino acid analogues. As an amino acid derivative, it is water-soluble and can be administered orally or via injection. The compound's pharmacokinetic properties are characteristic of amino acids and their derivatives. It is commercially available as an ergot supplement. The compound's stability in biological fluids and its metabolism follow pathways typical of branched-chain amino acids. Its interactions with transporters and metabolic enzymes influence its distribution and elimination.
Toxicity/Toxicokinetics
Specific toxicity data for gamma-Methylleucine is not extensively reported in the literature. As an amino acid derivative and dietary supplement component, it is generally considered to have a favorable safety profile at typical concentrations. The compound has been utilized commercially as an ergot supplement, suggesting acceptable safety for its intended uses. However, comprehensive toxicological studies would be required for therapeutic applications. Standard safety precautions should be taken when handling the compound in research settings.
References

[1]. Effects of amino acid derivatives on physical, mental, and physiological activities. Crit Rev Food Sci Nutr. 2015;55(13):1793-1144.

Additional Infomation
gamma-Methylleucine is a leucine derivative that modulates mTOR signaling and protein synthesis. It improves peptide binding to the Y2 receptor and enhances anorectic activity. The compound decreases endothelin-1 biological activity while maintaining high affinity for ETA and ETB receptors. It has been utilized commercially as an ergot supplement. gamma-Methylleucine plays a role in protein synthesis regulation and cellular metabolism, with potential implications for muscle physiology and metabolic health.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C7H15NO2
Molecular Weight
145.2
Exact Mass
145.11
CAS #
57224-50-7
PubChem CID
194032
Appearance
White to off-white solid powder
Density
1.0±0.1 g/cm3
Boiling Point
226.1±23.0 °C at 760 mmHg
Flash Point
90.6±22.6 °C
Vapour Pressure
0.0±0.9 mmHg at 25°C
Index of Refraction
1.449
LogP
0.97
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
3
Heavy Atom Count
10
Complexity
126
Defined Atom Stereocenter Count
1
SMILES
CC(C)(C)C[C@@H](C(=O)O)N
InChi Key
LPBSHGLDBQBSPI-YFKPBYRVSA-N
InChi Code
InChI=1S/C7H15NO2/c1-7(2,3)4-5(8)6(9)10/h5H,4,8H2,1-3H3,(H,9,10)/t5-/m0/s1
Chemical Name
(2S)-2-amino-4,4-dimethylpentanoic acid
Synonyms
Neopentylglycine; gamma-Methyl-L-leucine; gamma-Methylleucine
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)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 6.8871 mL 34.4353 mL 68.8705 mL
5 mM 1.3774 mL 6.8871 mL 13.7741 mL
10 mM 0.6887 mL 3.4435 mL 6.8871 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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