| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
G0/G1 switch 2 (G0s2) - transcriptional inhibitor (IC50 = 2.25 μM).
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| ln Vitro |
Hsd17b4 is bound by NS-3-008; overexpression of Hsd17b4 causes G0s2 mRNA expression, but Hsd17b4 knockdown decreases G0s2 mRNA levels. One way to counteract the inhibitory impact of NS-3-008 is to delete the Stat5 binding site in the G0s2 promoter or knock down Hsd17b4. Stat5's nuclear phosphorylation is decreased by NS-3-008 [1].
In vitro studies demonstrate that NS-3-008 is a novel, orally active transcriptional inhibitor of G0/G1 switch 2 (G0s2) with an IC50 of 2.25 μM. G0s2 is a protein involved in the regulation of cell cycle progression and lipid metabolism, and its dysregulation has been implicated in various diseases including chronic kidney disease. By inhibiting the transcription of G0s2, NS-3-008 reduces G0s2 mRNA and protein levels. The compound also exhibits inhibitory effects on Hsd17b4 and Stat5 signaling, suggesting additional mechanisms of action that may contribute to its biological effects. These properties make NS-3-008 a valuable tool for studying the role of G0s2 in cellular metabolism and disease. |
| ln Vivo |
G0s2 and Ccl2 mRNA levels in the kidney of wild-type 5/6Nx mice were reduced after 4 weeks of oral NS-3-008 (5 mg/kg) therapy. Phosphorylation of the proteins Stat5 and p65, as well as SUN concentration and renal caspase 3/7 activity, were all decreased in 5/6Nx animals given NS-03-08 treatment. The F4/80-positive region and F4/80 protein levels were decreased in 5/6Nx mice given NS-3-008 treatment [1].
In vivo studies have demonstrated that NS-3-008 decreases levels of G0s2 and Ccl2 mRNA in the kidneys when administered at 5 mg/kg via oral administration. This effect supports the compound's potential for studying chronic kidney disease, a condition in which G0s2 dysregulation and inflammation play important roles. The compound's oral bioavailability and ability to modulate G0s2 expression in the kidneys make it a valuable research tool for investigating the pathophysiology of kidney disease and for exploring therapeutic strategies targeting G0s2. Further studies are needed to fully characterize the compound's efficacy in various disease models and its long-term effects. |
| Enzyme Assay |
For transcriptional inhibition studies, cell-based assays are performed using cells that express G0s2 (such as kidney epithelial cells or other relevant cell lines). Cells are treated with NS-3-008 at various concentrations, and G0s2 mRNA levels are measured by quantitative RT-PCR. The IC50 for inhibition of G0s2 transcription is calculated from dose-response curves. Protein levels of G0s2 are assessed by Western blotting to confirm target engagement. Effects on Ccl2, Hsd17b4, and Stat5 are assessed using similar methods. The compound's effects on cell cycle progression and lipid metabolism are evaluated using flow cytometry and biochemical assays.
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| Cell Assay |
Cellular assays for NS-3-008 typically involve culturing kidney epithelial cells or other relevant cell lines and treating them with the compound at various concentrations. G0s2 mRNA levels are measured by quantitative RT-PCR, and G0s2 protein levels are assessed by Western blotting. Cell cycle progression is analyzed by flow cytometry after propidium iodide staining. Lipid metabolism is assessed by measuring lipid accumulation using Oil Red O staining or by measuring fatty acid oxidation rates. Inflammatory markers such as Ccl2 are measured by ELISA or quantitative RT-PCR. Cytotoxicity against mammalian cells is assessed in parallel using MTT or CellTiter-Glo assays.
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| Animal Protocol |
In vivo efficacy of NS-3-008 is evaluated in animal models of chronic kidney disease. Mice or rats are treated with NS-3-008 via oral administration at doses such as 5 mg/kg, and G0s2 and Ccl2 mRNA levels in the kidneys are measured by quantitative RT-PCR. Renal function is assessed by measuring serum creatinine and blood urea nitrogen (BUN) levels. Kidney histopathology is performed to assess inflammation, fibrosis, and tissue damage. The compound's effects on Hsd17b4 and Stat5 signaling are assessed by Western blotting or immunohistochemistry. These studies help establish the compound's potential for treating kidney disease and other conditions involving G0s2 dysregulation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NS-3-008 have been characterized to support its use as an orally active research tool. The compound's molecular weight of 269.81 (as the hydrochloride salt) and chemical properties influence its absorption, distribution, metabolism, and excretion (ADME) characteristics. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following oral administration. The compound's ability to reach the kidneys, a target organ for its effects on G0s2 expression, is important for its efficacy in kidney disease models.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of NS-3-008 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs including the kidneys. As a transcriptional inhibitor, potential effects on gene expression and cellular function are carefully monitored. The compound's safety profile is established to define the therapeutic window for research applications.
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| References |
[1]. Matsunaga N, et al. Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease. EBioMedicine. 2016 Nov;13:262-273.
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| Additional Infomation |
NS-3-008 HCl is a research tool compound used for studying the role of G0/G1 switch 2 (G0s2) in cellular metabolism, inflammation, and kidney disease. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves transcriptional inhibition of G0s2, which reduces G0s2 mRNA and protein levels and modulates downstream signaling pathways including Ccl2, Hsd17b4, and Stat5. This compound is valuable for investigating the pathophysiology of chronic kidney disease and for exploring therapeutic strategies targeting G0s2 and related pathways.
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| Molecular Formula |
C14H24CLN3
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|---|---|
| Molecular Weight |
269.813462257385
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| Exact Mass |
269.165
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| Elemental Analysis |
C, 62.32 H, 8.97 Cl, 13.14 N, 15.57
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| CAS # |
1172854-54-4
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| Related CAS # |
1172854-54-4;1172854-54-4 (HCl);
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| PubChem CID |
45053078
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
18
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| Complexity |
208
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCNC(=NCC1=CC=CC=C1)N.Cl
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| InChi Key |
UMIOAATZOCKZTH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H23N3.ClH/c1-2-3-4-8-11-16-14(15)17-12-13-9-6-5-7-10-13/h5-7,9-10H,2-4,8,11-12H2,1H3,(H3,15,16,17)1H
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| Chemical Name |
1-benzyl-3-hexylguanidine hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : ~125 mg/mL (~463.29 mM)
H2O : ~125 mg/mL (~463.29 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.71 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 (7.71 mM) (saturation unknown) 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. 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 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10 mg/mL (37.06 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7063 mL | 18.5316 mL | 37.0631 mL | |
| 5 mM | 0.7413 mL | 3.7063 mL | 7.4126 mL | |
| 10 mM | 0.3706 mL | 1.8532 mL | 3.7063 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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