NS-3-008 is a novel and orally bioactive transcriptional inhibitor of G0/G1 switch 2 (G0s2). NS-3-008 can be used for chronic kidney disease. NS-3-008 inhibited the transcription of G0s2 with a half-maximal inhibitory concentration (IC50) of 2.25 μM. Moreover, treatment of wild-type 5/6Nx mice with NS-3-008 (5 mg/kg, P.O.) resulted in decreased levels of G0s2 and Ccl2 mRNA in the kidneys.
Physicochemical Properties
| Molecular Formula | C14H24CLN3 |
| Molecular Weight | 269.813462257385 |
| Exact Mass | 269.165 |
| Elemental Analysis | C, 62.32 H, 8.97 Cl, 13.14 N, 15.57 |
| CAS # | 1172854-54-4 |
| Related CAS # | 1172854-54-4;1172854-54-4 (HCl); |
| PubChem CID | 45053078 |
| Appearance | Off-white to light yellow solid powder |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 18 |
| Complexity | 208 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | UMIOAATZOCKZTH-UHFFFAOYSA-N |
| 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 |
| Chemical Name | 1-benzyl-3-hexylguanidine 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 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) |
Biological Activity
| 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]. |
| 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]. |
| 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. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~463.29 mM) H2O : ~125 mg/mL (~463.29 mM) |
| 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. 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. 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 corn oil and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |