| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
iNOS (inducible nitric oxide synthase). L-NIL inhibits iNOS catalytic activity, reducing nitric oxide production from L-arginine. It shows approximately 28-fold selectivity for iNOS (IC50 3.3 µM) over the constitutive neuronal NOS (IC50 92 µM) and has weaker activity against endothelial NOS.
|
|---|---|
| ln Vitro |
L-NIL inhibited rat brain constitutive NOS (rcNOS) and mouse inducible NOS in a concentration-dependent manner, with the inhibition of mouse inducible NOS being substantially stronger. L-NIL was 28 times more selective for mouse inducible NOS, as seen by its IC50 values of 3.3 and 92 pM for rcNOS and mouse inducible NOS, respectively. Furthermore, L-NIL has a potency against induced NOS in mice that is about six times greater than that of L-NMA or L-NNA [3].
L-NIL inhibits mouse iNOS with an IC50 of 3.3 µM and rat brain constitutive NOS with an IC50 of 92 µM, showing approximately 28-fold selectivity for iNOS. It inhibits human iNOS with an IC50 of 5.9 µM. It exhibits about 10-fold greater inhibitory potency than NG-monomethyl-L-arginine. |
| ln Vivo |
In mice with renal IR, L-NIL (10 and 30 mg/kg, IP) inhibits autophagy, oxidative stress, and inflammation [1].
In vivo, L-NIL reduces iNOS activity and inflammatory tissue damage in adjuvant-induced arthritis, experimental osteoarthritis, and melanoma models. Oral administration in drinking water (0.15%) decreases serum nitrite levels after LPS challenge. It reduces joint swelling, radiographic changes, and chondrocyte apoptosis in arthritis models. |
| Enzyme Assay |
iNOS inhibition is measured using recombinant iNOS and L-arginine in the presence of NADPH and cofactors. Nitrite accumulation is quantified by the Griess assay. Compound is pre-incubated with enzyme, and the reaction is initiated by L-arginine. IC50 values are derived from dose-response curves. Selectivity is assessed against eNOS and nNOS.
|
| Cell Assay |
Macrophages or iNOS-expressing cells are stimulated with LPS and cytokines in the presence or absence of serial dilutions of L-NIL. Nitrite accumulation in culture supernatants is measured by Griess assay. iNOS protein expression is assessed by immunoblotting, and cell viability is measured in parallel.
|
| Animal Protocol |
Animal/Disease Models: Adult male Balb/c (20-25 g) [1].
Doses: 10 and 30 mg/kg. Route of Administration: intraperitoneal (ip) injection at the end of CLP and 6 hrs (hrs (hours)) after sepsis induction. Experimental Results: The increase in plasma NGAL was negligible compared to sham-operated mice. Resulting in a significant decrease in TLR4 and IL1β protein levels and clusterin transcripts. NFAT5 mRNA levels were increased compared to mice treated with vehicle. Promoted reduction in AR protein expression compared to vehicle-treated animals. Rodent models of inflammation, arthritis, or melanoma are used. L-NIL is administered in drinking water (0.15%) or by intraperitoneal injection at doses guided by pharmacokinetic studies. Plasma nitrite/nitrate levels, joint swelling, histopathology, and tumor growth are assessed. Tissue iNOS activity is measured ex vivo. |
| References |
|
| Molecular Formula |
C8H17N3O2.HCL
|
|---|---|
| Molecular Weight |
223.70042
|
| Exact Mass |
259.085
|
| CAS # |
150403-89-7
|
| Related CAS # |
L-NIL;53774-63-3;L-NIL dihydrochloride;159190-45-1
|
| PubChem CID |
9794509
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
369ºC at 760 mmHg
|
| Melting Point |
253-255ºC
|
| Flash Point |
177ºC
|
| Vapour Pressure |
1.86E-06mmHg at 25°C
|
| LogP |
2.95
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
14
|
| Complexity |
192
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC(=N)NCCCC[C@@H](C(=O)O)N.Cl
|
| InChi Key |
HJYWSATZDBEAOS-FJXQXJEOSA-N
|
| InChi Code |
InChI=1S/C8H17N3O2.ClH/c1-6(9)11-5-3-2-4-7(10)8(12)13;/h7H,2-5,10H2,1H3,(H2,9,11)(H,12,13);1H/t7-;/m0./s1
|
| Chemical Name |
(2S)-2-amino-6-(1-aminoethylideneamino)hexanoic acid;hydrochloride
|
| 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 (In Vitro) |
DMSO: ~100 mg/mL (~447.0 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (11.18 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: 2.5 mg/mL (11.18 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: 2.5 mg/mL (11.18 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4703 mL | 22.3514 mL | 44.7027 mL | |
| 5 mM | 0.8941 mL | 4.4703 mL | 8.9405 mL | |
| 10 mM | 0.4470 mL | 2.2351 mL | 4.4703 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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