| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Arginase and p70 ribosomal S6 kinase 1 (p70S6K1). L-Norvaline is an arginase inhibitor that enhances nitric oxide (NO) production and reduces oxidative stress. Also inhibits p70S6K1 kinase, a key regulator of protein synthesis and cell growth.
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| ln Vitro |
Arginase inhibitor that enhances NO production and reduces oxidative stress. Improves insulin resistance, demonstrates antioxidant and anti-hyperglycemic properties. Inhibits p70S6K1 kinase, involved in protein synthesis, cell growth, and proliferation. Increases sphingosine kinase 2 (SPHK2) levels, leading to increased sphingosine 1-phosphate (S1P), a neuroprotective factor.
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| ln Vivo |
Reverses cognitive decline in Alzheimer's disease mouse models. Neuroprotective as indicated by reduced beta-amyloidosis, alleviated microgliosis, and reduced TNF-alpha transcription. Through these modes, has potential to improve AD symptoms and interfere with pathogenesis. Also exhibits anti-inflammatory and antioxidant effects in vivo.
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| Enzyme Assay |
(1) Arginase inhibition: incubate bovine liver arginase (0.1-1 U) with L-arginine (10-100 mM) and L-Norvaline (0.01-1000 uM) in 50 mM Tris-HCl pH9.5 at 37degC for 60 min. (2) Stop with 3M H2SO4, measure urea by colorimetric assay (diacetyl monoxime/antipyrine at 540 nm), calculate IC50. (3) p70S6K1 inhibition: incubate recombinant p70S6K1 (0.01-0.1 ug) with S6 peptide substrate, ATP (10 uM), and L-Norvaline (0.1-1000 uM) in 50 mM Tris-HCl pH7.5, 10 mM MgCl2 at 30degC for 30 min, measure phosphorylated substrate by HTRF.
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| Cell Assay |
(1) Seed neuronal cells (SH-SY5Y, primary cortical neurons) in 96-well plates (5,000-10,000/well). (2) For neuroprotection: treat with L-Norvaline (10-1000 uM) for 1-2 h before adding Abeta1-42 oligomers (5-10 uM) or H2O2 (100-500 uM). (3) After 24-48 h, MTT/CCK-8 for viability. (4) For apoptosis: stain with Annexin V-FITC/PI after 24 h. (5) For NO: treat macrophages (RAW 264.7) with L-Norvaline (10-1000 uM) for 1 h, then LPS (1 ug/mL) for 24 h, measure nitrite by Griess. (6) For p70S6K1: treat cells with L-Norvaline (100-1000 uM) for 1-6 h, Western blot for phospho-p70S6K (Thr389) and phospho-S6.
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| Animal Protocol |
(1) For Alzheimer's: use 8-12 week old male APP/PS1 transgenic mice (20-25 g). (2) Administer L-Norvaline IP (50-200 mg/kg) or oral (100-500 mg/kg) daily for 3-6 months in sterile saline/PBS. (3) Perform behavioral tests (Y-maze, Morris water maze, novel object recognition, passive avoidance) at baseline and intervals. (4) At endpoint, collect brains and blood. (5) Histology: stain with Congo red or Thioflavin S for Abeta plaques, IHC for Abeta, IBA-1, GFAP, NeuN. (6) Biochemistry: brain homogenate ELISA for Abeta40/Abeta42, measure oxidative stress (MDA, 8-OHdG, SOD, catalase) and inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). (7) Western blot for arginase, p70S6K, phospho-p70S6K, S1P. (8) For metabolic studies: high-fat diet-fed mice, administer L-Norvaline (100-500 mg/kg PO daily) for 8-12 weeks, measure blood glucose, OGTT, insulin, HOMA-IR, lipid profile.
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| ADME/Pharmacokinetics |
Soluble in water (≥20 mg/mL) and 1M HCl. For cell culture, dissolve directly or prepare 50-200 mM stock in water, adjust pH to 7.0-7.4 with NaOH, filter sterilize. For in vivo, dissolve in sterile saline or PBS at 20-100 mg/mL. Storage: powder at -20degC for 3 years; solution at -20degC for 6 months, -80degC for 1 year. PK in rodents (IP 100 mg/kg): Cmax 1-2 mM, t1/2 1-2 h. Oral bioavailability 40-60%.
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| Toxicity/Toxicokinetics |
In vitro: CCK-8 on HEK293 cells with L-Norvaline 0.5-50 mM, 48 h, IC50 >20 mM. In vivo: acute IP LD50 in mice ~1000-2000 mg/kg; oral LD50 >2000 mg/kg. High doses (>500 mg/kg IP) cause mild sedation and GI distress. Chronic (100-200 mg/kg/day for 3-6 months) in AD models well tolerated, no significant weight loss or organ toxicity. No teratogenic or mutagenic effects. For research use only.
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| Additional Infomation |
L-2-Aminovaleric acid is a 2-aminovaleric acid with an S-configuration. It is a bacterial metabolite with hypoglycemic and neuroprotective effects. It is the enantiomer of D-2-aminovaleric acid and also the zwitterion tautomer of L-2-aminovaleric acid.
N-valine is an isomer of the more common amino acid valine. N-valine has been reported to exist in Daphnia pulex, Serratia marcescens, and Paraburkholderia, and relevant data are available for reference. L-Norvaline is a non-proteinogenic amino acid, isomer of valine. Potent arginase inhibitor, increasing L-arginine availability for nitric oxide synthase (NOS), enhancing NO production, vasodilation, and reducing inflammation. Also inhibits p70S6K1 kinase. In Alzheimer's disease models, reverses cognitive decline, reduces beta-amyloidosis, alleviates microgliosis, and reduces TNF-alpha. Also improves insulin resistance, exhibits antioxidant and anti-hyperglycemic properties. Not FDA-approved; under investigation for AD, metabolic syndrome, and conditions involving arginase dysregulation. For research use only. |
| Molecular Formula |
C5H11NO2
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|---|---|
| Molecular Weight |
117.15
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| Exact Mass |
117.078
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| CAS # |
6600-40-4
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| Related CAS # |
L-Norvaline-d5;1202936-50-2
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| PubChem CID |
65098
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
222.9±23.0 °C at 760 mmHg
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| Melting Point |
300ºC
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| Flash Point |
88.6±22.6 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.464
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| LogP |
0.38
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
8
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| Complexity |
82.5
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC[C@@H](C(=O)O)N
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| InChi Key |
SNDPXSYFESPGGJ-BYPYZUCNSA-N
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| InChi Code |
InChI=1S/C5H11NO2/c1-2-3-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1
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| Chemical Name |
(2S)-2-aminopentanoic 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) |
H2O :< 0.1 mg/mL
DMSO :< 1 mg/mL |
|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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 : PEG300 ：Tween 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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 8.5361 mL | 42.6803 mL | 85.3606 mL | |
| 5 mM | 1.7072 mL | 8.5361 mL | 17.0721 mL | |
| 10 mM | 0.8536 mL | 4.2680 mL | 8.5361 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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